Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.1.1 Summary of Adverse Events by Enrollment Group
Safety Population: IC1
1
30-59 ml/min per 1.73m >60 ml/min per 1.73m
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Number of Events/Participants
Number of Adverse Events 1 0 3 5 6 15
Participants with at least one AE
1 (33.3%) 0 2 (66.7%) 2 (40.0%) 2 (66.7%) 7 (46.7%)
Number of SAEs 0 0 0 1 0 1
Participants with at least one SAE
0 0 0 1 (20.0%) 0 1 (6.7%)
Severity (All AEs)
Mild 1 0 3 4 4 12
Moderate 0 0 0 1 2 3
Highest Severity Per Participant
Mild 1 (33.3%) 0 2 (66.7%) 1 (20.0%) 0 4 (26.7%)
Moderate 0 0 0 1 (20.0%) 2 (66.7%) 3 (20.0%)
Relationship (All AEs)
Not related 1 0 1 3 5 10
Related 0 0 2 2 1 5
Strongest Relationship Per Participant
Not related 1 (33.3%) 0 1 (33.3%) 1 (20.0%) 1 (33.3%) 4 (26.7%)
Related 0 0 1 (33.3%) 1 (20.0%) 1 (33.3%) 3 (20.0%)
Severity (All SAEs)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.1.1 Summary of Adverse Events by Enrollment Group
Safety Population: IC1
2
30-59 ml/min per 1.73m >60 ml/min per 1.73m
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Mild 0 0 0 1 0 1
Relationship (All SAEs)
Not related 0 0 0 1 0 1
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.1.2 Summary of Adverse Events by Enrollment Group
Safety Population: IC2
1
30-59 ml/min per 1.73m >60 ml/min per 1.73m
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Number of Events/Participants
Number of Adverse Events 1 6 4 1 12
Participants with at least one AE 1 (50.0%) 1 (50.0%) 2 (40.0%) 1 (50.0%) 5 (45.5%)
Severity (All AEs)
Mild 1 5 4 0 10
Moderate 0 1 0 1 2
Highest Severity Per Participant
Mild 1 (50.0%) 0 2 (40.0%) 0 3 (27.3%)
Moderate 0 1 (50.0%) 0 1 (50.0%) 2 (18.2%)
Relationship (All AEs)
Not related 1 6 4 1 12
Strongest Relationship Per Participant
Not related 1 (50.0%) 1 (50.0%) 2 (40.0%) 1 (50.0%) 5 (45.5%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.2.1 Adverse Events by System Organ Class, Preferred Term and Enrollment Group
Safety Population
1
30-59 ml/min per 1.73m >60 ml/min per 1.73m
0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=3) 0.1 mg/kg/day
(N=8) 0.2 mg/kg/day
(N=7) 0.4 mg/kg/day
(N=3) Total
(N=26)
System Organ Class Preferred Term
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Blood and lymphatic system disorders
1 (20%) 1 0 0 0 0 0 0 0 0 1 (3.8%) 1
Anaemia 1 (20%) 1 0 0 0 0 0 0 0 0 1 (3.8%) 1
Gastrointestinal disorders
0
0
1 (33.3%)
5
1 (12.5%)
2
2 (28.6%)
2
1 (33.3%)
1
5 (19.2%)
10
Abdominal pain upper 0 0 1 (33.3%) 2 1 (12.5%) 1 0 0 0 0 2 (7.7%) 3
Diarrhoea 0 0 1 (33.3%) 1 0 0 1 (14.3%) 1 0 0 2 (7.7%) 2
Nausea 0 0 0 0 1 (12.5%) 1 1 (14.3%) 1 0 0 2 (7.7%) 2
Retching 0 0 1 (33.3%) 2 0 0 0 0 0 0 1 (3.8%) 2
Vomiting 0 0 0 0 0 0 0 0 1 (33.3%) 1 1 (3.8%) 1
General disorders and administration site conditions
0
0
0
0
2 (25%)
3
0
0
0
0
2 (7.7%)
3
Infusion site extravasation
0 0 0 0 1 (12.5%) 1 0 0 0 0 1 (3.8%) 1
Infusion site pain 0 0 0 0 1 (12.5%) 1 0 0 0 0 1 (3.8%) 1
Infusion site pruritus 0 0 0 0 1 (12.5%) 1 0 0 0 0 1 (3.8%) 1
Infections and infestations
0
0
0
0
0
0
2 (28.6%)
2
0
0
2 (7.7%)
2
Gastroenteritis 0 0 0 0 0 0 1 (14.3%) 1 0 0 1 (3.8%) 1
Otitis externa 0 0 0 0 0 0 1 (14.3%) 1 0 0 1 (3.8%) 1
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.2.1 Adverse Events by System Organ Class, Preferred Term and Enrollment Group
Safety Population
2
30-59 ml/min per 1.73m >60 ml/min per 1.73m
0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=3) 0.1 mg/kg/day
(N=8) 0.2 mg/kg/day
(N=7) 0.4 mg/kg/day
(N=3) Total
(N=26)
System Organ Class Preferred Term
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Injury, poisoning and procedural complications
1 (20%)
1
0
0
0
0
0
0
1 (33.3%)
1
2 (7.7%)
2
Arthropod sting 1 (20%) 1 0 0 0 0 0 0 0 0 1 (3.8%) 1
Upper limb fracture 0 0 0 0 0 0 0 0 1 (33.3%) 1 1 (3.8%) 1
Investigations
0
0
0
0
0
0
0
0
2 (66.7%)
4
2 (7.7%)
4
Glomerular filtration rate decreased
0 0 0 0 0 0 0 0 1 (33.3%) 1 1 (3.8%) 1
Haemoglobin decreased
0 0 0 0 0 0 0 0 1 (33.3%) 1 1 (3.8%) 1
Immunoglobulins abnormal
0 0 0 0 0 0 0 0 1 (33.3%) 1 1 (3.8%) 1
Neutrophil count decreased
0 0 0 0 0 0 0 0 1 (33.3%) 1 1 (3.8%) 1
Nervous system disorders
0
0
1 (33.3%)
1
1 (12.5%)
1
1 (14.3%)
2
0
0
3 (11.5%)
4
Dizziness 0 0 0 0 0 0 1 (14.3%) 2 0 0 1 (3.8%) 2
Headache 0 0 1 (33.3%) 1 1 (12.5%) 1 0 0 0 0 2 (7.7%) 2
Skin and subcutaneous tissue disorders
0
0
0
0
1 (12.5%)
1
0
0
0
0
1 (3.8%)
1
Rash 0 0 0 0 1 (12.5%) 1 0 0 0 0 1 (3.8%) 1
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.3 Adverse Events by System Organ Class, Preferred Term, Severity and by Enrollment Group
Safety Population
Note: The percentages are based on the total number of participants in each treatment group or total.
Participants are counted once at each System Organ Class and Preferred Term levels using the highest severity. 1
30-59 ml/min per 1.73m >60 ml/min per 1.73m
System Organ Class Preferred Term Severity
0.1 mg/kg/day (N=5)
0.2 mg/kg/day (N=3)
0.1 mg/kg/day (N=8)
0.2 mg/kg/day (N=7)
0.4 mg/kg/day (N=3)
Total (N=26)
Blood and lymphatic system disorders Mild 1 (20.0%) 0 0 0 0 1 (3.8%)
Anaemia Mild 1 (20.0%) 0 0 0 0 1 (3.8%)
Gastrointestinal disorders Mild 0 0 1 (12.5%) 1 (14.3%) 0 2 (7.7%)
Moderate 0 1 (33.3%) 0 1 (14.3%) 1 (33.3%) 3 (11.5%)
Abdominal pain upper Mild 0 1 (33.3%) 1 (12.5%) 0 0 2 (7.7%)
Diarrhoea Mild 0 1 (33.3%) 0 0 0 1 (3.8%)
Moderate 0 0 0 1 (14.3%) 0 1 (3.8%)
Nausea Mild 0 0 1 (12.5%) 1 (14.3%) 0 2 (7.7%)
Retching Moderate 0 1 (33.3%) 0 0 0 1 (3.8%)
Vomiting Moderate 0 0 0 0 1 (33.3%) 1 (3.8%)
General disorders and administration site conditions Mild 0 0 2 (25.0%) 0 0 2 (7.7%)
Infusion site extravasation Mild 0 0 1 (12.5%) 0 0 1 (3.8%)
Infusion site pain Mild 0 0 1 (12.5%) 0 0 1 (3.8%)
Infusion site pruritus Mild 0 0 1 (12.5%) 0 0 1 (3.8%)
Infections and infestations Mild 0 0 0 2 (28.6%) 0 2 (7.7%)
Gastroenteritis Mild 0 0 0 1 (14.3%) 0 1 (3.8%)
Otitis externa Mild 0 0 0 1 (14.3%) 0 1 (3.8%)
Injury, poisoning and procedural complications Mild 1 (20.0%) 0 0 0 1 (33.3%) 2 (7.7%)
Arthropod sting Mild 1 (20.0%) 0 0 0 0 1 (3.8%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.3 Adverse Events by System Organ Class, Preferred Term, Severity and by Enrollment Group
Safety Population
Note: The percentages are based on the total number of participants in each treatment group or total.
Participants are counted once at each System Organ Class and Preferred Term levels using the highest severity. 2
30-59 ml/min per 1.73m >60 ml/min per 1.73m
System Organ Class Preferred Term Severity
0.1 mg/kg/day (N=5)
0.2 mg/kg/day (N=3)
0.1 mg/kg/day (N=8)
0.2 mg/kg/day (N=7)
0.4 mg/kg/day (N=3)
Total (N=26)
Upper limb fracture Mild 0 0 0 0 1 (33.3%) 1 (3.8%)
Investigations Mild 0 0 0 0 1 (33.3%) 1 (3.8%)
Moderate 0 0 0 0 1 (33.3%) 1 (3.8%)
Glomerular filtration rate decreased Moderate 0 0 0 0 1 (33.3%) 1 (3.8%)
Haemoglobin decreased Mild 0 0 0 0 1 (33.3%) 1 (3.8%)
Immunoglobulins abnormal Mild 0 0 0 0 1 (33.3%) 1 (3.8%)
Neutrophil count decreased Mild 0 0 0 0 1 (33.3%) 1 (3.8%)
Nervous system disorders Mild 0 1 (33.3%) 1 (12.5%) 0 0 2 (7.7%)
Moderate 0 0 0 1 (14.3%) 0 1 (3.8%)
Dizziness Moderate 0 0 0 1 (14.3%) 0 1 (3.8%)
Headache Mild 0 1 (33.3%) 1 (12.5%) 0 0 2 (7.7%)
Skin and subcutaneous tissue disorders Mild 0 0 1 (12.5%) 0 0 1 (3.8%)
Rash Mild 0 0 1 (12.5%) 0 0 1 (3.8%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.4 Adverse Events by System Organ Class, Preferred Term, Relationship to Study Medication and by Enrollment Group
Safety Population
Note: The percentages are based on the total number of participants in each treatment group or total.
Participants are counted once at each System Organ Class and Preferred Term levels using the closest relationship to study drug. 1
30-59 ml/min per 1.73m >60 ml/min per 1.73m
System Organ Class Preferred Term Relationship
0.1 mg/kg/day (N=5)
0.2 mg/kg/day (N=3)
0.1 mg/kg/day (N=8)
0.2 mg/kg/day (N=7)
0.4 mg/kg/day (N=3)
Total (N=26)
Blood and lymphatic system disorders Not related 1 (20.0%) 0 0 0 0 1 (3.8%)
Anaemia Not related 1 (20.0%) 0 0 0 0 1 (3.8%)
Gastrointestinal disorders Not related 0 1 (33.3%) 0 1 (14.3%) 1 (33.3%) 3 (11.5%)
Related 0 0 1 (12.5%) 1 (14.3%) 0 2 (7.7%)
Abdominal pain upper Not related 0 1 (33.3%) 0 0 0 1 (3.8%)
Related 0 0 1 (12.5%) 0 0 1 (3.8%)
Diarrhoea Not related 0 1 (33.3%) 0 1 (14.3%) 0 2 (7.7%)
Nausea Related 0 0 1 (12.5%) 1 (14.3%) 0 2 (7.7%)
Retching Not related 0 1 (33.3%) 0 0 0 1 (3.8%)
Vomiting Not related 0 0 0 0 1 (33.3%) 1 (3.8%)
General disorders and administration site conditions Not related 0 0 2 (25.0%) 0 0 2 (7.7%)
Infusion site extravasation Not related 0 0 1 (12.5%) 0 0 1 (3.8%)
Infusion site pain Not related 0 0 1 (12.5%) 0 0 1 (3.8%)
Infusion site pruritus Not related 0 0 1 (12.5%) 0 0 1 (3.8%)
Infections and infestations Not related 0 0 0 2 (28.6%) 0 2 (7.7%)
Gastroenteritis Not related 0 0 0 1 (14.3%) 0 1 (3.8%)
Otitis externa Not related 0 0 0 1 (14.3%) 0 1 (3.8%)
Injury, poisoning and procedural complications Not related 1 (20.0%) 0 0 0 1 (33.3%) 2 (7.7%)
Arthropod sting Not related 1 (20.0%) 0 0 0 0 1 (3.8%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.4 Adverse Events by System Organ Class, Preferred Term, Relationship to Study Medication and by Enrollment Group
Safety Population
Note: The percentages are based on the total number of participants in each treatment group or total.
Participants are counted once at each System Organ Class and Preferred Term levels using the closest relationship to study drug. 2
30-59 ml/min per 1.73m >60 ml/min per 1.73m
System Organ Class Preferred Term Relationship
0.1 mg/kg/day (N=5)
0.2 mg/kg/day (N=3)
0.1 mg/kg/day (N=8)
0.2 mg/kg/day (N=7)
0.4 mg/kg/day (N=3)
Total (N=26)
Upper limb fracture Not related 0 0 0 0 1 (33.3%) 1 (3.8%)
Investigations Not related 0 0 0 0 1 (33.3%) 1 (3.8%)
Related 0 0 0 0 1 (33.3%) 1 (3.8%)
Glomerular filtration rate decreased Related 0 0 0 0 1 (33.3%) 1 (3.8%)
Haemoglobin decreased Not related 0 0 0 0 1 (33.3%) 1 (3.8%)
Immunoglobulins abnormal Not related 0 0 0 0 1 (33.3%) 1 (3.8%)
Neutrophil count decreased Not related 0 0 0 0 1 (33.3%) 1 (3.8%)
Nervous system disorders Not related 0 1 (33.3%) 1 (12.5%) 0 0 2 (7.7%)
Related 0 0 0 1 (14.3%) 0 1 (3.8%)
Dizziness Related 0 0 0 1 (14.3%) 0 1 (3.8%)
Headache Not related 0 1 (33.3%) 1 (12.5%) 0 0 2 (7.7%)
Skin and subcutaneous tissue disorders Not related 0 0 1 (12.5%) 0 0 1 (3.8%)
Rash Not related 0 0 1 (12.5%) 0 0 1 (3.8%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.1.5 Adverse Events Listed by Most Frequent Preferred Term and by Enrollment Group
Safety Population
Events that occurred in 5% or more participants are included.
1
30-59 ml/min per 1.73m >60 ml/min per 1.73m
0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=3) 0.1 mg/kg/day
(N=8) 0.2 mg/kg/day
(N=7) 0.4 mg/kg/day
(N=3) Total
(N=26)
System Organ Class
Preferred Term
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Participants with Event
N (%)
Total Events
N
Gastrointestinal disorders
Abdominal pain upper
0 0 1 (33.3%) 2 1 (12.5%) 1 0 0 0 0 2 (7.7%) 3
Gastrointestinal disorders
Diarrhoea 0 0 1 (33.3%) 1 0 0 1 (14.3%) 1 0 0 2 (7.7%) 2
Nervous system disorders
Headache 0 0 1 (33.3%) 1 1 (12.5%) 1 0 0 0 0 2 (7.7%) 2
Gastrointestinal disorders
Nausea 0 0 0 0 1 (12.5%) 1 1 (14.3%) 1 0 0 2 (7.7%) 2
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.1.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Hematology
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Hematocrit (%)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 40.5 (3.7) 41.3 41.6 (2.4) 37.2 (3.9) 38.4 (4.5) 39.3 (3.7)
Median (Min, Max) 41.6 (36.4, 43.5) 41.3 (41.3, 41.3) 41.0 (39.6, 44.3) 39.0 (31.0, 40.2) 39.4 (33.4, 42.3) 40.0 (31.0, 44.3)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 38.5 (2.8) 43.7 38.9 (3.1) 35.8 (2.1) 38.6 (6.4) 38.0 (3.4)
Median (Min, Max) 39.1 (35.4, 41.0) 43.7 (43.7, 43.7) 39.8 (35.4, 41.5) 34.8 (33.7, 38.8) 38.6 (34.1, 43.1) 38.0 (33.7, 43.7)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) -2.0 (0.9) 2.4 -2.7 (4.1) -1.4 (2.6) -2.3 (4.3) -1.7 (2.8)
Median (Min, Max) -2.5 (-2.5, -1.0) 2.4 (2.4, 2.4) -4.5 (-5.6, 1.9) -1.4 (-4.2, 2.7) -2.3 (-5.3, 0.8) -2.0 (-5.6, 2.7)
95% CI for Median 1 (-4.2, 1.9)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) -4.8 (1.8) 5.8 -6.3 (9.8) -3.3 (7.3) -5.8 (10.8) -4.0 (7.1)
Median (Min, Max) -5.8 (-6.0, -2.7) 5.8 (5.8, 5.8) -10.2 (-13.7, 4.8) -3.9 (-10.8, 8.7) -5.8 (-13.5, 1.9) -4.8 (-13.7, 8.7)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.1.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Hematology
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Hemoglobin (g/dL)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 13.4 (1.0) 14.5 13.4 (1.0) 12.4 (1.3) 13.2 (1.9) 13.1 (1.3)
Median (Min, Max) 13.8 (12.3, 14.2) 14.5 (14.5, 14.5) 13.6 (12.3, 14.3) 12.9 (10.7, 13.9) 13.2 (11.3, 15.0) 13.2 (10.7, 15.0)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 12.9 (0.8) 15.1 12.3 (1.3) 11.7 (1.0) 12.4 (1.7) 12.4 (1.3)
Median (Min, Max) 13.3 (12.0, 13.3) 15.1 (15.1, 15.1) 12.6 (10.9, 13.4) 11.3 (10.9, 13.1) 12.4 (11.2, 13.6) 12.5 (10.9, 15.1)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) -0.6 (0.3) 0.6 -1.1 (0.8) -0.7 (0.9) -1.7 (0.4) -0.8 (0.8)
Median (Min, Max) -0.5 (-0.9, -0.3) 0.6 (0.6, 0.6) -1.4 (-1.7, -0.2) -0.6 (-2.0, 0.6) -1.7 (-2.0, -1.4) -0.7 (-2.0, 0.6)
95% CI for Median 1 (-1.4, -0.2)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) -4.1 (2.0) 4.1 -8.3 (5.9) -5.1 (7.5) -12.2 (4.1) -5.9 (6.4)
Median (Min, Max) -3.6 (-6.3, -2.4) 4.1 (4.1, 4.1) -11.4 (-11.9, -1.5) -5.2 (-15.5, 5.6) -12.2 (-15.2, -9.3) -5.5 (-15.5, 5.6)
Participant with at least one newly emergent abnormal finding
0 1 (100.0%) 1 (33.3%) 1 (20.0%) 1 (33.3%) 4 (26.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.1.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Hematology
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Platelets (103/µL)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 247.7 (66.4) 280.0 304.7 (127.6) 279.8 (74.3) 269.7 (67.1) 276.3 (74.4)
Median (Min, Max) 216.0 (203.0, 324.0) 280.0 (280.0, 280.0) 253.0 (211.0, 450.0) 249.0 (206.0, 392.0) 235.0 (227.0, 347.0) 249.0 (203.0, 450.0)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 262.7 (67.6) 250.0 226.7 (62.6) 266.2 (80.2) 258.0 (66.5) 254.6 (62.2)
Median (Min, Max) 267.0 (193.0, 328.0) 250.0 (250.0, 250.0) 213.0 (172.0, 295.0) 262.0 (168.0, 362.0) 258.0 (211.0, 305.0) 256.0 (168.0, 362.0)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) 15.0 (32.0) -30.0 -78.0 (174.4) -13.6 (85.7) -29.0 (18.4) -24.6 (90.5)
Median (Min, Max) 4.0 (-10.0, 51.0) -30.0 (-30.0, -30.0) 2.0 (-278.0, 42.0) -38.0 (-130.0, 91.0) -29.0 (-42.0, -16.0) -13.0 (-278.0, 91.0)
95% CI for Median 1 (-38.0, 47.0)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) 6.6 (15.0) -10.7 -14.7 (41.5) -2.7 (28.9) -9.6 (3.6) -4.8 (24.9)
Median (Min, Max) 1.2 (-4.9, 23.6) -10.7 (-10.7, -10.7) 1.0 (-61.8, 16.6) -15.3 (-33.2, 38.4) -9.6 (-12.1, -7.0) -6.0 (-61.8, 38.4)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.1.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Hematology
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
WBC (103/µL)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 6.9 (2.9) 5.3 8.7 (3.2) 7.7 (2.4) 6.6 (1.4) 7.3 (2.4)
Median (Min, Max) 8.4 (3.5, 8.7) 5.3 (5.3, 5.3) 7.5 (6.2, 12.3) 7.9 (3.8, 9.9) 6.9 (5.1, 7.9) 7.5 (3.5, 12.3)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 7.7 (1.9) 4.4 9.0 (2.5) 5.7 (1.8) 4.8 (0.9) 6.6 (2.3)
Median (Min, Max) 7.7 (5.8, 9.6) 4.4 (4.4, 4.4) 8.2 (7.0, 11.8) 5.4 (3.9, 8.5) 4.8 (4.2, 5.4) 6.1 (3.9, 11.8)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) 0.8 (3.5) -0.9 0.3 (0.7) -2.0 (2.1) -1.7 (2.8) -0.8 (2.3)
Median (Min, Max) 1.2 (-2.9, 4.2) -0.9 (-0.9, -0.9) 0.7 (-0.5, 0.8) -1.5 (-5.2, 0.1) -1.7 (-3.7, 0.3) -0.7 (-5.2, 4.2)
95% CI for Median 1 (-2.6, 0.8)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) 33.6 (78.0) -16.2 5.9 (9.2) -22.0 (22.0) -20.1 (37.5) -3.4 (41.6)
Median (Min, Max) 14.3 (-32.9, 119.4) -16.2 (-16.2, -16.2) 8.8 (-4.4, 13.2) -14.7 (-54.5, 2.6) -20.1 (-46.6, 6.5) -7.8 (-54.5, 119.4)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.1.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Hematology
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Hematocrit (%)
Pre-dose value
N 2 2 4 2 10
Mean (SD) 33.1 (2.1) 37.2 (7.1) 40.8 (4.3) 33.8 (0.2) 37.1 (4.9)
Median (Min, Max) 33.1 (31.6, 34.5) 37.2 (32.2, 42.2) 41.6 (35.8, 44.4) 33.8 (33.6, 33.9) 35.2 (31.6, 44.4)
Post-dose value
N 2 2 4 1 9
Mean (SD) 30.8 (4.5) 36.8 (10.1) 41.0 (1.3) 31.9 36.8 (6.0)
Median (Min, Max) 30.8 (27.6, 34.0) 36.8 (29.6, 43.9) 40.8 (39.6, 42.6) 31.9 (31.9, 31.9) 39.6 (27.6, 43.9)
Change from Baseline
N 2 2 3 1 8
Mean (SD) -2.3 (2.5) -0.5 (3.0) -1.6 (4.8) -1.7 -1.5 (3.0)
Median (Min, Max) -2.3 (-4.0, -0.5) -0.5 (-2.6, 1.7) -4.0 (-4.8, 3.9) -1.7 (-1.7, -1.7) -2.2 (-4.8, 3.9)
95% CI for Median 1 (-4.0, 3.9)
Percentage Change
N 2 2 3 1 8
Mean (SD) -7.1 (7.9) -2.0 (8.6) -3.3 (11.6) -5.1 -4.1 (7.9)
Median (Min, Max) -7.1 (-12.7, -1.4) -2.0 (-8.1, 4.0) -9.0 (-10.8, 10.1) -5.1 (-5.1, -5.1) -6.6 (-12.7, 10.1)
Participant with at least one newly emergent abnormal finding
0 1 (50.0%) 0 1 (50.0%) 2 (18.2%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.1.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Hematology
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Hemoglobin (g/dL)
Pre-dose value
N 2 2 4 2 10
Mean (SD) 11.1 (0.8) 12.4 (1.8) 13.4 (1.6) 11.2 (0.0) 12.3 (1.6)
Median (Min, Max) 11.1 (10.5, 11.7) 12.4 (11.1, 13.6) 13.8 (11.3, 14.8) 11.2 (11.2, 11.2) 11.5 (10.5, 14.8)
Post-dose value
N 2 2 4 1 9
Mean (SD) 10.2 (1.6) 11.7 (2.6) 13.3 (0.3) 10.8 12.0 (1.8)
Median (Min, Max) 10.2 (9.1, 11.3) 11.7 (9.8, 13.5) 13.3 (13.1, 13.7) 10.8 (10.8, 10.8) 13.1 (9.1, 13.7)
Change from Baseline
N 2 2 3 1 8
Mean (SD) -0.9 (0.7) -0.7 (0.8) -0.9 (1.0) -0.4 -0.8 (0.7)
Median (Min, Max) -0.9 (-1.4, -0.4) -0.7 (-1.3, -0.1) -1.3 (-1.7, 0.2) -0.4 (-0.4, -0.4) -0.9 (-1.7, 0.2)
95% CI for Median 1 (-1.4, 0.2)
Percentage Change
N 2 2 3 1 8
Mean (SD) -8.4 (7.0) -6.2 (7.8) -6.3 (6.9) -3.6 -6.5 (5.6)
Median (Min, Max) -8.4 (-13.3, -3.4) -6.2 (-11.7, -0.7) -9.0 (-11.5, 1.5) -3.6 (-3.6, -3.6) -6.3 (-13.3, 1.5)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.1.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Hematology
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Platelets (103/µL)
Pre-dose value
N 2 2 4 2 10
Mean (SD) 276.5 (53.0) 259.0 (19.8) 327.5 (101.8) 264.0 (19.8) 290.9 (69.9)
Median (Min, Max) 276.5 (239.0, 314.0) 259.0 (245.0, 273.0) 293.5 (247.0, 476.0) 264.0 (250.0, 278.0) 275.5 (239.0, 476.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 223.5 (13.4) 248.0 (4.2) 201.3 (46.0) 244.0 221.3 (35.5)
Median (Min, Max) 223.5 (214.0, 233.0) 248.0 (245.0, 251.0) 211.0 (139.0, 244.0) 244.0 (244.0, 244.0) 233.0 (139.0, 251.0)
Change from Baseline
N 2 2 3 1 8
Mean (SD) -53.0 (39.6) -11.0 (15.6) -56.0 (53.0) -34.0 -41.3 (38.2)
Median (Min, Max) -53.0 (-81.0, -25.0) -11.0 (-22.0, 0.0) -56.0 (-109.0, -3.0) -34.0 (-34.0, -34.0) -29.5 (-109.0, 0.0)
95% CI for Median 1 (-81.0, 0.0)
Percentage Change
N 2 2 3 1 8
Mean (SD) -18.1 (10.8) -4.0 (5.7) -18.9 (17.3) -12.2 -14.2 (12.3)
Median (Min, Max) -18.1 (-25.8, -10.5) -4.0 (-8.1, 0.0) -19.9 (-35.7, -1.2) -12.2 (-12.2, -12.2) -11.4 (-35.7, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.1.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Hematology
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
WBC (103/µL)
Pre-dose value
N 2 2 4 2 10
Mean (SD) 8.9 (0.8) 4.4 (1.3) 7.9 (0.9) 8.8 (0.3) 7.6 (1.9)
Median (Min, Max) 8.9 (8.3, 9.4) 4.4 (3.5, 5.3) 8.2 (6.6, 8.7) 8.8 (8.6, 9.0) 8.3 (3.5, 9.4)
Post-dose value
N 2 2 4 1 9
Mean (SD) 7.3 (1.6) 4.2 (0.7) 6.3 (1.5) 6.3 6.1 (1.6)
Median (Min, Max) 7.3 (6.2, 8.4) 4.2 (3.7, 4.7) 6.6 (4.2, 7.6) 6.3 (6.3, 6.3) 6.2 (3.7, 8.4)
Change from Baseline
N 2 2 3 1 8
Mean (SD) -1.5 (2.3) -0.2 (0.6) -0.7 (1.5) -2.3 -1.0 (1.4)
Median (Min, Max) -1.5 (-3.2, 0.1) -0.2 (-0.6, 0.2) -0.3 (-2.3, 0.6) -2.3 (-2.3, -2.3) -0.5 (-3.2, 0.6)
95% CI for Median 1 (-2.3, 0.6)
Percentage Change
N 2 2 3 1 8
Mean (SD) -16.0 (25.0) -2.4 (11.8) -7.5 (18.8) -27.0 -10.8 (16.8)
Median (Min, Max) -16.0 (-33.6, 1.7) -2.4 (-10.7, 6.0) -4.2 (-27.7, 9.5) -27.0 (-27.0, -27.0) -7.5 (-33.6, 9.5)
Participant with at least one newly emergent abnormal finding
0 1 (50.0%) 0 0 1 (9.1%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
1
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Bands (%)
Pre-dose value
N 0 0 0 0 1 1
Mean (SD) 0.0 0.0
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Post-dose value
N 1 0 2 2 0 5
Mean (SD) 0.0 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Basophils (%)
Pre-dose value
N 3 1 3 4 2 13
Mean (SD) 0.1 (0.2) 0.7 0.3 (0.2) 0.2 (0.3) 0.6 (0.4) 0.3 (0.3)
Median (Min, Max) 0.0 (0.0, 0.3) 0.7 (0.7, 0.7) 0.3 (0.1, 0.5) 0.2 (0.0, 0.6) 0.6 (0.3, 0.8) 0.3 (0.0, 0.8)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 0.1 (0.2) 0.0 0.3 (0.6) 0.6 (0.5) 0.5 (0.7) 0.4 (0.5)
Median (Min, Max) 0.0 (0.0, 0.4) 0.0 (0.0, 0.0) 0.0 (0.0, 1.0) 1.0 (0.0, 1.0) 0.5 (0.0, 1.0) 0.0 (0.0, 1.0)
Change from Baseline
N 3 1 3 4 1 12
Mean (SD) 0.0 (0.1) -0.7 0.0 (0.4) 0.3 (0.8) -0.8 -0.0 (0.6)
Median (Min, Max) 0.0 (0.0, 0.1) -0.7 (-0.7, -0.7) -0.1 (-0.3, 0.5) 0.4 (-0.6, 1.0) -0.8 (-0.8, -0.8) -0.1 (-0.8, 1.0)
95% CI for Median 1 (-0.6, 0.5)
Percentage Change
N 1 1 3 2 1 8
Mean (SD) 33.3 -100.0 -33.3 (115.5) -100.0 (0.0) -100.0 -58.3 (79.2)
Median (Min, Max) 33.3 (33.3, 33.3) -100.0 (-100.0, -100.0) -100.0 (-100.0, 100.0) -100.0 (-100.0, -100.0) -100.0 (-100.0, -100.0) -100.0 (-100.0, 100.0)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
3
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Blasts (%)
Pre-dose value
N 0 0 0 0 1 1
Mean (SD) 0.0 0.0
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Post-dose value
N 1 0 2 2 0 5
Mean (SD) 0.0 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Eosinophils (%)
Pre-dose value
N 3 1 3 4 3 14
Mean (SD) 1.2 (0.7) 5.2 2.4 (1.7) 1.6 (1.5) 3.1 (1.7) 2.3 (1.6)
Median (Min, Max) 1.0 (0.7, 2.0) 5.2 (5.2, 5.2) 2.1 (0.9, 4.3) 1.7 (0.0, 3.0) 2.2 (2.0, 5.0) 2.1 (0.0, 5.2)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 2.2 (2.4) 3.0 2.0 (1.0) 5.8 (4.5) 5.0 (2.8) 3.9 (3.3)
Median (Min, Max) 1.0 (0.7, 5.0) 3.0 (3.0, 3.0) 2.0 (1.0, 3.0) 6.0 (1.0, 13.0) 5.0 (3.0, 7.0) 3.0 (0.7, 13.0)
Change from Baseline
N 3 1 3 4 2 13
Mean (SD) 1.0 (2.6) -2.2 -0.4 (0.8) 2.4 (1.0) 1.4 (0.8) 0.9 (1.9)
Median (Min, Max) 0.0 (-1.0, 4.0) -2.2 (-2.2, -2.2) -0.1 (-1.3, 0.1) 2.7 (1.0, 3.2) 1.4 (0.8, 2.0) 0.8 (-2.2, 4.0)
95% CI for Median 1 (-1.0, 3.0)
Percentage Change
N 3 1 3 3 2 12
Mean (SD) 116.7 (246.6) -42.3 -8.0 (20.9) 204.8 (169.2) 38.2 (2.6) 81.2 (157.3)
Median (Min, Max) 0.0 (-50.0, 400.0) -42.3 (-42.3, -42.3) -4.8 (-30.2, 11.1) 114.3 (100.0, 400.0) 38.2 (36.4, 40.0) 23.7 (-50.0, 400.0)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 1 (33.3%) 2 (13.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
5
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Lymphocytes (%)
Pre-dose value
N 3 1 3 4 3 14
Mean (SD) 19.6 (17.0) 31.8 44.4 (8.3) 31.6 (11.0) 40.1 (25.0) 33.6 (16.2)
Median (Min, Max) 12.8 (7.0, 39.0) 31.8 (31.8, 31.8) 43.1 (36.8, 53.2) 31.2 (21.0, 43.0) 42.6 (14.0, 63.8) 37.9 (7.0, 63.8)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 17.7 (5.5) 24.0 48.0 (4.0) 42.4 (7.8) 53.5 (12.0) 38.6 (14.6)
Median (Min, Max) 18.0 (12.0, 23.0) 24.0 (24.0, 24.0) 48.0 (44.0, 52.0) 46.0 (30.0, 50.0) 53.5 (45.0, 62.0) 44.5 (12.0, 62.0)
Change from Baseline
N 3 1 3 4 2 13
Mean (SD) -1.9 (18.5) -7.8 3.6 (6.6) 8.9 (11.7) 14.6 (23.2) 4.8 (13.8)
Median (Min, Max) -0.8 (-21.0, 16.0) -7.8 (-7.8, -7.8) 0.9 (-1.2, 11.2) 6.8 (-3.0, 25.0) 14.6 (-1.8, 31.0) 0.9 (-21.0, 31.0)
95% CI for Median 1 (-3.0, 16.0)
Percentage Change
N 3 1 3 4 2 13
Mean (SD) 56.2 (151.2) -24.5 10.1 (17.8) 39.6 (55.0) 109.3 (158.6) 42.4 (90.2)
Median (Min, Max) -6.3 (-53.8, 228.6) -24.5 (-24.5, -24.5) 2.1 (-2.3, 30.4) 23.1 (-7.0, 119.0) 109.3 (-2.8, 221.4) 2.1 (-53.8, 228.6)
Participant with at least one newly emergent abnormal finding
3 (100.0%) 1 (100.0%) 2 (66.7%) 0 0 6 (40.0%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
6
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Metamyelocytes (%)
Pre-dose value
N 0 0 0 0 1 1
Mean (SD) 0.0 0.0
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Post-dose value
N 1 0 2 2 0 5
Mean (SD) 0.0 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
7
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Monocytes (%)
Pre-dose value
N 3 1 3 4 2 13
Mean (SD) 9.0 (5.6) 5.6 6.1 (1.0) 5.8 (1.7) 8.9 (1.2) 7.1 (2.9)
Median (Min, Max) 8.1 (4.0, 15.0) 5.6 (5.6, 5.6) 5.9 (5.2, 7.2) 5.6 (4.0, 8.0) 8.9 (8.0, 9.7) 5.9 (4.0, 15.0)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 5.6 (1.5) 12.0 6.3 (1.5) 7.6 (2.3) 6.5 (0.7) 7.1 (2.2)
Median (Min, Max) 6.0 (4.0, 6.9) 12.0 (12.0, 12.0) 6.0 (5.0, 8.0) 8.0 (4.0, 10.0) 6.5 (6.0, 7.0) 7.0 (4.0, 12.0)
Change from Baseline
N 3 1 3 4 1 12
Mean (SD) -3.4 (6.8) 6.4 0.2 (2.2) 1.2 (1.1) -1.0 0.1 (4.1)
Median (Min, Max) -1.2 (-11.0, 2.0) 6.4 (6.4, 6.4) 0.8 (-2.2, 2.1) 1.1 (0.0, 2.6) -1.0 (-1.0, -1.0) 0.9 (-11.0, 6.4)
95% CI for Median 1 (-1.2, 2.1)
Percentage Change
N 3 1 3 4 1 12
Mean (SD) -12.7 (61.7) 114.3 6.8 (33.9) 20.3 (20.4) -12.5 13.8 (47.1)
Median (Min, Max) -14.8 (-73.3, 50.0) 114.3 (114.3, 114.3) 15.4 (-30.6, 35.6) 16.6 (0.0, 48.1) -12.5 (-12.5, -12.5) 13.9 (-73.3, 114.3)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
8
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Myelocytes (%)
Pre-dose value
N 0 0 0 0 1 1
Mean (SD) 0.0 0.0
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Post-dose value
N 1 0 2 2 0 5
Mean (SD) 0.0 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
9
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Neutrophils (%)
Pre-dose value
N 2 1 1 3 2 9
Mean (SD) 61.6 (23.4) 56.3 48.7 64.3 (13.4) 35.2 (14.1) 54.6 (16.9)
Median (Min, Max) 61.6 (45.0, 78.1) 56.3 (56.3, 56.3) 48.7 (48.7, 48.7) 69.8 (49.0, 74.0) 35.2 (25.2, 45.1) 49.0 (25.2, 78.1)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 74.0 (5.6) 62.0 43.3 (5.9) 44.0 (12.1) 34.0 (9.9) 50.1 (16.4)
Median (Min, Max) 73.0 (69.0, 80.0) 62.0 (62.0, 62.0) 41.0 (39.0, 50.0) 47.0 (27.0, 59.0) 34.0 (27.0, 41.0) 48.0 (27.0, 80.0)
Change from Baseline
N 2 1 1 3 1 8
Mean (SD) 15.0 (18.5) 5.7 1.3 -15.6 (8.1) 1.8 -1.0 (15.5)
Median (Min, Max) 15.0 (1.9, 28.0) 5.7 (5.7, 5.7) 1.3 (1.3, 1.3) -11.0 (-25.0, -10.8) 1.8 (1.8, 1.8) 1.6 (-25.0, 28.0)
95% CI for Median 1 (-11.0, 28.0)
Percentage Change
N 2 1 1 3 1 8
Mean (SD) 32.3 (42.3) 10.1 2.7 -23.9 (9.2) 7.1 1.6 (29.0)
Median (Min, Max) 32.3 (2.4, 62.2) 10.1 (10.1, 10.1) 2.7 (2.7, 2.7) -22.5 (-33.8, -15.5) 7.1 (7.1, 7.1) 2.6 (-33.8, 62.2)
Participant with at least one newly emergent abnormal finding
2 (66.7%) 0 0 1 (20.0%) 1 (33.3%) 4 (26.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
10
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Nucleated RBC (%)
Pre-dose value
N 0 0 1 0 1 2
Mean (SD) 2.3 0.0 1.2 (1.6)
Median (Min, Max) 2.3 (2.3, 2.3) 0.0 (0.0, 0.0) 1.2 (0.0, 2.3)
Post-dose value
N 1 0 2 2 0 5
Mean (SD) 0.0 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Change from Baseline
N 0 0 1 0 0 1
Mean (SD) -2.3 -2.3
Median (Min, Max) -2.3 (-2.3, -2.3) -2.3 (-2.3, -2.3)
95% CI for Median 1 (., .)
Percentage Change
N 0 0 1 0 0 1
Mean (SD) -100.0 -100.0
Median (Min, Max) -100.0 (-100.0, -100.0) -100.0 (-100.0, -100.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
11
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Plasma cells (%)
Pre-dose value
N 0 0 0 0 1 1
Mean (SD) 0.0 0.0
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Post-dose value
N 1 0 2 2 0 5
Mean (SD) 0.0 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
12
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Promyelocytes (%)
Pre-dose value
N 0 0 0 0 1 1
Mean (SD) 0.0 0.0
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Post-dose value
N 1 0 2 2 0 5
Mean (SD) 0.0 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Bands (%)
Post-dose value
N 1 1 1 1 4
Mean (SD) 0.0 0.0 0.0 0.0 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Basophils (%)
Pre-dose value
N 2 2 3 2 9
Mean (SD) 0.3 (0.1) 0.9 (0.2) 0.3 (0.5) 0.2 (0.2) 0.4 (0.4)
Median (Min, Max) 0.3 (0.2, 0.3) 0.9 (0.7, 1.0) 0.0 (0.0, 0.9) 0.2 (0.0, 0.3) 0.3 (0.0, 1.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 0.0 (0.0) 0.5 (0.7) 0.3 (0.5) 0.0 0.2 (0.4)
Median (Min, Max) 0.0 (0.0, 0.0) 0.5 (0.0, 1.0) 0.0 (0.0, 1.0) 0.0 (0.0, 0.0) 0.0 (0.0, 1.0)
Change from Baseline
N 2 2 3 1 8
Mean (SD) -0.3 (0.1) -0.4 (0.5) 0.0 (0.1) 0.0 -0.1 (0.3)
Median (Min, Max) -0.3 (-0.3, -0.2) -0.4 (-0.7, 0.0) 0.0 (0.0, 0.1) 0.0 (0.0, 0.0) 0.0 (-0.7, 0.1)
95% CI for Median 1 (-0.3, 0.1)
Percentage Change
N 2 2 1 0 5
Mean (SD) -100.0 (0.0) -50.0 (70.7) 11.1 -57.8 (57.9)
Median (Min, Max) -100.0 (-100.0, -100.0) -50.0 (-100.0, 0.0) 11.1 (11.1, 11.1) -100.0 (-100.0, 11.1)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Blasts (%)
Post-dose value
N 1 1 1 1 4
Mean (SD) 0.0 0.0 0.0 0.0 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Eosinophils (%)
Pre-dose value
N 2 2 3 2 9
Mean (SD) 2.8 (0.4) 3.2 (1.1) 2.0 (1.0) 2.0 (1.4) 2.4 (1.0)
Median (Min, Max) 2.8 (2.5, 3.1) 3.2 (2.4, 4.0) 2.0 (1.0, 3.0) 2.0 (1.0, 3.0) 2.5 (1.0, 4.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 1.0 (0.0) 5.5 (4.9) 2.0 (0.8) 1.0 2.4 (2.6)
Median (Min, Max) 1.0 (1.0, 1.0) 5.5 (2.0, 9.0) 2.0 (1.0, 3.0) 1.0 (1.0, 1.0) 2.0 (1.0, 9.0)
Change from Baseline
N 2 2 3 1 8
Mean (SD) -1.8 (0.4) 2.3 (3.8) -0.3 (0.6) 0.0 0.0 (2.2)
Median (Min, Max) -1.8 (-2.1, -1.5) 2.3 (-0.4, 5.0) 0.0 (-1.0, 0.0) 0.0 (0.0, 0.0) -0.2 (-2.1, 5.0)
95% CI for Median 1 (-1.5, 5.0)
Percentage Change
N 2 2 3 1 8
Mean (SD) -63.9 (5.5) 54.2 (100.2) -11.1 (19.2) 0.0 -6.6 (59.6)
Median (Min, Max) -63.9 (-67.7, -60.0) 54.2 (-16.7, 125.0) 0.0 (-33.3, 0.0) 0.0 (0.0, 0.0) -8.3 (-67.7, 125.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
5
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Lymphocytes (%)
Pre-dose value
N 2 2 4 2 10
Mean (SD) 27.0 (6.2) 40.7 (17.9) 31.3 (6.5) 33.4 (6.2) 32.7 (9.0)
Median (Min, Max) 27.0 (22.6, 31.3) 40.7 (28.0, 53.3) 30.0 (25.0, 40.0) 33.4 (29.0, 37.8) 30.2 (22.6, 53.3)
Post-dose value
N 2 2 4 1 9
Mean (SD) 29.5 (12.0) 37.5 (14.8) 35.0 (6.2) 52.0 36.2 (10.2)
Median (Min, Max) 29.5 (21.0, 38.0) 37.5 (27.0, 48.0) 35.5 (27.0, 42.0) 52.0 (52.0, 52.0) 36.0 (21.0, 52.0)
Change from Baseline
N 2 2 3 1 8
Mean (SD) 2.6 (5.9) -3.2 (3.0) 2.7 (13.6) 23.0 3.7 (11.2)
Median (Min, Max) 2.6 (-1.6, 6.7) -3.2 (-5.3, -1.0) 10.0 (-13.0, 11.0) 23.0 (23.0, 23.0) 2.9 (-13.0, 23.0)
95% CI for Median 1 (-5.3, 23.0)
Percentage Change
N 2 2 3 1 8
Mean (SD) 7.2 (20.1) -6.8 (4.5) 14.3 (41.0) 79.3 15.4 (35.8)
Median (Min, Max) 7.2 (-7.1, 21.4) -6.8 (-9.9, -3.6) 31.3 (-32.5, 44.0) 79.3 (79.3, 79.3) 8.9 (-32.5, 79.3)
Participant with at least one newly emergent abnormal finding
0 1 (50.0%) 0 1 (50.0%) 2 (18.2%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
6
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Metamyelocytes (%)
Post-dose value
N 1 1 1 1 4
Mean (SD) 0.0 0.0 0.0 0.0 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
7
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Monocytes (%)
Pre-dose value
N 2 2 4 2 10
Mean (SD) 5.7 (1.8) 6.7 (0.5) 7.9 (5.4) 4.9 (2.7) 6.6 (3.5)
Median (Min, Max) 5.7 (4.4, 7.0) 6.7 (6.3, 7.0) 7.2 (2.0, 15.0) 4.9 (3.0, 6.8) 6.6 (2.0, 15.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 7.5 (2.1) 7.0 (8.5) 5.5 (3.1) 4.0 6.1 (3.8)
Median (Min, Max) 7.5 (6.0, 9.0) 7.0 (1.0, 13.0) 5.5 (2.0, 9.0) 4.0 (4.0, 4.0) 6.0 (1.0, 13.0)
Change from Baseline
N 2 2 3 1 8
Mean (SD) 1.8 (0.3) 0.4 (9.0) -1.1 (1.2) 1.0 0.2 (3.7)
Median (Min, Max) 1.8 (1.6, 2.0) 0.4 (-6.0, 6.7) -1.0 (-2.4, 0.0) 1.0 (1.0, 1.0) 0.5 (-6.0, 6.7)
95% CI for Median 1 (-2.4, 6.7)
Percentage Change
N 2 2 3 1 8
Mean (SD) 32.5 (5.5) 10.3 (135.8) -16.7 (19.1) 33.3 8.6 (57.2)
Median (Min, Max) 32.5 (28.6, 36.4) 10.3 (-85.7, 106.3) -12.5 (-37.5, 0.0) 33.3 (33.3, 33.3) 14.3 (-85.7, 106.3)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
8
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Myelocytes (%)
Post-dose value
N 1 1 1 1 4
Mean (SD) 0.0 0.0 0.0 0.0 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
9
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Neutrophils (%)
Pre-dose value
N 2 1 2 2 7
Mean (SD) 64.1 (3.7) 61.0 60.5 (16.3) 59.5 (10.6) 61.3 (8.3)
Median (Min, Max) 64.1 (61.5, 66.7) 61.0 (61.0, 61.0) 60.5 (49.0, 72.0) 59.5 (52.0, 67.0) 61.5 (49.0, 72.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 61.5 (10.6) 50.0 (17.0) 57.3 (6.2) 44.0 55.1 (9.9)
Median (Min, Max) 61.5 (54.0, 69.0) 50.0 (38.0, 62.0) 56.5 (52.0, 64.0) 44.0 (44.0, 44.0) 54.0 (38.0, 69.0)
Change from Baseline
N 2 1 2 1 6
Mean (SD) -2.6 (6.9) 1.0 2.0 (18.4) -23.0 -3.9 (13.0)
Median (Min, Max) -2.6 (-7.5, 2.3) 1.0 (1.0, 1.0) 2.0 (-11.0, 15.0) -23.0 (-23.0, -23.0) -3.3 (-23.0, 15.0)
95% CI for Median 1 (-23.0, 15.0)
Percentage Change
N 2 1 2 1 6
Mean (SD) -4.4 (11.1) 1.6 7.7 (32.4) -34.3 -4.4 (21.9)
Median (Min, Max) -4.4 (-12.2, 3.4) 1.6 (1.6, 1.6) 7.7 (-15.3, 30.6) -34.3 (-34.3, -34.3) -5.3 (-34.3, 30.6)
Participant with at least one newly emergent abnormal finding
1 (50.0%) 0 1 (20.0%) 0 2 (18.2%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
10
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Nucleated RBC (%)
Post-dose value
N 1 1 1 1 4
Mean (SD) 0.0 0.0 0.0 0.0 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
11
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Plasma cells (%)
Post-dose value
N 1 1 1 1 4
Mean (SD) 0.0 0.0 0.0 0.0 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.2.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Differential
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
12
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Promyelocytes (%)
Post-dose value
N 1 1 1 1 4
Mean (SD) 0.0 0.0 0.0 0.0 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Albumin (g/dL)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 4.3 (0.4) 4.4 4.4 (0.2) 4.4 (0.1) 4.5 (0.1) 4.4 (0.2)
Median (Min, Max) 4.5 (3.9, 4.6) 4.4 (4.4, 4.4) 4.4 (4.2, 4.5) 4.4 (4.3, 4.5) 4.5 (4.4, 4.6) 4.4 (3.9, 4.6)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 4.2 (0.2) 4.2 4.3 (0.3) 4.3 (0.2) 4.3 (0.1) 4.3 (0.2)
Median (Min, Max) 4.1 (4.1, 4.5) 4.2 (4.2, 4.2) 4.5 (4.0, 4.5) 4.2 (4.0, 4.6) 4.3 (4.2, 4.4) 4.2 (4.0, 4.6)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) -0.1 (0.3) -0.2 -0.0 (0.2) -0.1 (0.3) -0.3 (0.1) -0.1 (0.2)
Median (Min, Max) -0.1 (-0.4, 0.2) -0.2 (-0.2, -0.2) 0.0 (-0.2, 0.1) -0.2 (-0.3, 0.3) -0.3 (-0.3, -0.2) -0.2 (-0.4, 0.3)
95% CI for Median 1 (-0.3, 0.1)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) -2.0 (7.0) -4.6 -0.8 (3.6) -3.1 (5.8) -5.5 (1.6) -2.8 (4.7)
Median (Min, Max) -2.2 (-8.9, 5.1) -4.6 (-4.5, -4.5) 0.0 (-4.8, 2.3) -4.6 (-7.0, 7.0) -5.5 (-6.7, -4.3) -4.5 (-8.9, 7.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Alkaline phosphatase (U/L)
Pre-dose value
N 3 1 1 4 3 12
Mean (SD) 234.0 (138.0) 146.0 228.0 129.5 (54.8) 131.7 (119.4) 165.8 (96.6)
Median (Min, Max) 164.0 (145.0, 393.0) 146.0 (146.0, 146.0) 228.0 (228.0, 228.0) 138.0 (57.0, 185.0) 162.0 (0.0, 233.0) 158.0 (0.0, 393.0)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 210.7 (106.0) 158.0 165.3 (73.7) 130.4 (47.7) 174.5 (68.6) 163.4 (67.7)
Median (Min, Max) 164.0 (136.0, 332.0) 158.0 (158.0, 158.0) 154.0 (98.0, 244.0) 137.0 (60.0, 181.0) 174.5 (126.0, 223.0) 156.0 (60.0, 332.0)
Change from Baseline
N 3 1 1 4 2 11
Mean (SD) -23.3 (32.9) 12.0 16.0 -11.8 (10.5) 58.0 (96.2) 2.5 (45.8)
Median (Min, Max) -9.0 (-61.0, 0.0) 12.0 (12.0, 12.0) 16.0 (16.0, 16.0) -14.5 (-21.0, 3.0) 58.0 (-10.0, 126.0) -9.0 (-61.0, 126.0)
95% CI for Median 1 (-17.0, 16.0)
Percentage Change
N 3 1 1 4 1 10
Mean (SD) -7.2 (7.8) 8.2 7.0 -6.7 (8.0) -4.3 -3.8 (8.5)
Median (Min, Max) -6.2 (-15.5, 0.0) 8.2 (8.2, 8.2) 7.0 (7.0, 7.0) -10.4 (-11.4, 5.3) -4.3 (-4.3, -4.3) -5.3 (-15.5, 8.2)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
ALT (U/L)
Pre-dose value
N 3 1 1 5 3 13
Mean (SD) 49.3 (42.1) 18.0 10.0 19.2 (7.1) 10.0 (10.0) 23.2 (23.8)
Median (Min, Max) 52.0 (6.0, 90.0) 18.0 (18.0, 18.0) 10.0 (10.0, 10.0) 21.0 (7.0, 25.0) 10.0 (0.0, 20.0) 20.0 (0.0, 90.0)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 34.0 (23.5) 12.0 11.3 (2.9) 16.2 (9.6) 9.0 (2.8) 17.6 (14.2)
Median (Min, Max) 45.0 (7.0, 50.0) 12.0 (12.0, 12.0) 13.0 (8.0, 13.0) 12.0 (7.0, 28.0) 9.0 (7.0, 11.0) 12.0 (7.0, 50.0)
Change from Baseline
N 3 1 1 5 2 12
Mean (SD) -15.3 (21.7) -6.0 -2.0 -3.0 (8.9) 4.0 (9.9) -5.1 (13.0)
Median (Min, Max) -7.0 (-40.0, 1.0) -6.0 (-6.0, -6.0) -2.0 (-2.0, -2.0) 0.0 (-16.0, 5.0) 4.0 (-3.0, 11.0) -2.5 (-40.0, 11.0)
95% CI for Median 1 (-8.0, 4.0)
Percentage Change
N 3 1 1 5 1 11
Mean (SD) -13.8 (30.6) -33.3 -20.0 -12.6 (37.9) -30.0 -17.1 (28.6)
Median (Min, Max) -13.5 (-44.4, 16.7) -33.3 (-33.3, -33.3) -20.0 (-20.0, -20.0) 0.0 (-64.0, 21.7) -30.0 (-30.0, -30.0) -20.0 (-64.0, 21.7)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
AST (U/L)
Pre-dose value
N 3 1 1 5 3 13
Mean (SD) 44.0 (42.3) 23.0 35.0 24.0 (8.6) 16.7 (14.7) 27.7 (21.6)
Median (Min, Max) 28.0 (12.0, 92.0) 23.0 (23.0, 23.0) 35.0 (35.0, 35.0) 25.0 (11.0, 33.0) 22.0 (0.0, 28.0) 25.0 (0.0, 92.0)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 30.3 (23.6) 17.0 19.0 (2.0) 20.6 (6.4) 19.5 (0.7) 21.9 (11.0)
Median (Min, Max) 28.0 (8.0, 55.0) 17.0 (17.0, 17.0) 19.0 (17.0, 21.0) 21.0 (12.0, 30.0) 19.5 (19.0, 20.0) 19.5 (8.0, 55.0)
Change from Baseline
N 3 1 1 5 2 12
Mean (SD) -13.7 (20.3) -6.0 -14.0 -3.4 (4.7) 8.5 (16.3) -5.1 (13.0)
Median (Min, Max) -4.0 (-37.0, 0.0) -6.0 (-6.0, -6.0) -14.0 (-14.0, -14.0) -3.0 (-11.0, 1.0) 8.5 (-3.0, 20.0) -3.5 (-37.0, 20.0)
95% CI for Median 1 (-11.0, 0.0)
Percentage Change
N 3 1 1 5 1 11
Mean (SD) -24.5 (21.5) -26.1 -40.0 -10.5 (17.4) -13.6 -18.7 (17.6)
Median (Min, Max) -33.3 (-40.2, 0.0) -26.1 (-26.1, -26.1) -40.0 (-40.0, -40.0) -9.1 (-36.7, 9.1) -13.6 (-13.6, -13.6) -16.0 (-40.2, 9.1)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
5
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Bicarbonate (mEq/L)
Pre-dose value
N 3 1 3 4 3 14
Mean (SD) 21.0 (1.0) 22.0 23.7 (1.2) 22.3 (3.9) 22.7 (0.6) 22.4 (2.2)
Median (Min, Max) 21.0 (20.0, 22.0) 22.0 (22.0, 22.0) 23.0 (23.0, 25.0) 21.5 (19.0, 27.0) 23.0 (22.0, 23.0) 22.5 (19.0, 27.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 20.0 (2.6) 22.0 21.3 (1.5) 20.4 (2.7) 20.7 (3.1) 20.7 (2.3)
Median (Min, Max) 21.0 (17.0, 22.0) 22.0 (22.0, 22.0) 21.0 (20.0, 23.0) 20.0 (17.0, 24.0) 20.0 (18.0, 24.0) 21.0 (17.0, 24.0)
Change from Baseline
N 3 1 3 4 3 14
Mean (SD) -1.0 (1.7) 0.0 -2.3 (2.5) -1.5 (4.4) -2.0 (3.6) -1.6 (2.9)
Median (Min, Max) 0.0 (-3.0, 0.0) 0.0 (0.0, 0.0) -2.0 (-5.0, 0.0) -1.0 (-7.0, 3.0) -3.0 (-5.0, 2.0) -1.0 (-7.0, 3.0)
95% CI for Median 1 (-3.0, 1.0)
Percentage Change
N 3 1 3 4 3 14
Mean (SD) -5.0 (8.7) 0.0 -9.6 (10.0) -4.8 (19.7) -8.6 (15.9) -6.3 (12.8)
Median (Min, Max) 0.0 (-15.0, 0.0) 0.0 (0.0, 0.0) -8.7 (-20.0, 0.0) -2.9 (-29.2, 15.8) -13.0 (-21.7, 9.1) -4.4 (-29.2, 15.8)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 1 (33.3%) 2 (13.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
6
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Bilirubin, direct (mg/dL)
Pre-dose value
N 1 1 0 4 3 9
Mean (SD) 0.2 0.3 0.1 (0.1) 0.1 (0.1) 0.1 (0.1)
Median (Min, Max) 0.2 (0.2, 0.2) 0.3 (0.3, 0.3) 0.1 (0.0, 0.2) 0.2 (0.0, 0.2) 0.2 (0.0, 0.3)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 0.2 (0.1) 0.2 0.2 (0.0) 0.2 (0.0) 0.2 (0.0) 0.2 (0.0)
Median (Min, Max) 0.2 (0.1, 0.2) 0.2 (0.2, 0.2) 0.2 (0.2, 0.2) 0.2 (0.2, 0.2) 0.2 (0.2, 0.2) 0.2 (0.1, 0.2)
Change from Baseline
N 1 1 0 4 2 8
Mean (SD) 0.0 -0.1 0.1 (0.1) 0.1 (0.1) 0.1 (0.1)
Median (Min, Max) 0.0 (0.0, 0.0) -0.1 (-0.1, -0.1) 0.1 (0.0, 0.2) 0.1 (0.0, 0.2) 0.0 (-0.1, 0.2)
95% CI for Median 1 (0.0, 0.2)
Percentage Change
N 1 1 0 2 1 5
Mean (SD) 0.0 -33.3 0.0 (0.0) 0.0 -6.7 (14.9)
Median (Min, Max) 0.0 (0.0, 0.0) -33.3 (-33.3, -33.3) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (-33.3, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
7
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Bilirubin, total (mg/dL)
Pre-dose value
N 3 1 1 5 3 13
Mean (SD) 0.4 (0.1) 0.4 0.7 0.3 (0.1) 0.1 (0.1) 0.3 (0.2)
Median (Min, Max) 0.4 (0.3, 0.4) 0.4 (0.4, 0.4) 0.7 (0.7, 0.7) 0.3 (0.2, 0.5) 0.2 (0.0, 0.2) 0.3 (0.0, 0.7)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 0.2 (0.2) 0.2 0.2 (0.2) 0.1 (0.1) 0.1 (0.0) 0.2 (0.1)
Median (Min, Max) 0.2 (0.1, 0.4) 0.2 (0.2, 0.2) 0.1 (0.1, 0.4) 0.1 (0.1, 0.2) 0.1 (0.1, 0.1) 0.1 (0.1, 0.4)
Change from Baseline
N 3 1 1 5 2 12
Mean (SD) -0.1 (0.2) -0.2 -0.3 -0.2 (0.2) 0.0 (0.1) -0.1 (0.1)
Median (Min, Max) -0.1 (-0.3, 0.0) -0.2 (-0.2, -0.2) -0.3 (-0.3, -0.3) -0.1 (-0.4, 0.0) 0.0 (-0.1, 0.1) -0.1 (-0.4, 0.1)
95% CI for Median 1 (-0.3, 0.0)
Percentage Change
N 3 1 1 5 1 11
Mean (SD) -36.1 (37.6) -50.0 -42.9 -46.0 (31.1) -50.0 -43.7 (26.4)
Median (Min, Max) -33.3 (-75.0, 0.0) -50.0 (-50.0, -50.0) -42.9 (-42.9, -42.9) -50.0 (-80.0, 0.0) -50.0 (-50.0, -50.0) -50.0 (-80.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
8
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Blood urea nitrogen (BUN) (mg/dL)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 28.3 (3.1) 16.0 14.7 (2.1) 14.4 (4.7) 13.7 (4.5) 17.2 (6.7)
Median (Min, Max) 29.0 (25.0, 31.0) 16.0 (16.0, 16.0) 14.0 (13.0, 17.0) 14.0 (9.0, 22.0) 14.0 (9.0, 18.0) 14.0 (9.0, 31.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 33.3 (2.9) 17.0 19.3 (4.0) 11.8 (1.3) 15.7 (4.0) 18.7 (8.5)
Median (Min, Max) 35.0 (30.0, 35.0) 17.0 (17.0, 17.0) 20.0 (15.0, 23.0) 12.0 (10.0, 13.0) 18.0 (11.0, 18.0) 17.0 (10.0, 35.0)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) 5.0 (1.0) 1.0 4.7 (4.7) -2.6 (4.4) 2.0 (2.0) 1.5 (4.5)
Median (Min, Max) 5.0 (4.0, 6.0) 1.0 (1.0, 1.0) 3.0 (1.0, 10.0) -2.0 (-9.0, 3.0) 2.0 (0.0, 4.0) 2.0 (-9.0, 10.0)
95% CI for Median 1 (-1.0, 4.0)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) 17.9 (4.3) 6.3 33.9 (37.6) -11.7 (28.3) 16.9 (15.0) 10.2 (28.0)
Median (Min, Max) 20.0 (12.9, 20.7) 6.3 (6.3, 6.3) 17.7 (7.1, 76.9) -15.4 (-40.9, 33.3) 22.2 (0.0, 28.6) 12.9 (-40.9, 76.9)
Participant with at least one newly emergent abnormal finding
0 0 2 (66.7%) 0 0 2 (13.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
9
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Calcium (mg/dL)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 10.0 (0.5) 9.8 10.2 (0.2) 9.5 (0.4) 9.7 (0.3) 9.8 (0.4)
Median (Min, Max) 10.1 (9.5, 10.4) 9.8 (9.8, 9.8) 10.2 (10.0, 10.3) 9.4 (9.1, 10.0) 9.8 (9.4, 9.9) 9.8 (9.1, 10.4)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 9.9 (0.1) 10.4 9.9 (0.2) 9.5 (0.5) 9.8 (0.2) 9.8 (0.4)
Median (Min, Max) 9.9 (9.8, 10.0) 10.4 (10.4, 10.4) 10.0 (9.7, 10.1) 9.4 (9.0, 10.2) 9.9 (9.6, 10.0) 9.9 (9.0, 10.4)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) -0.1 (0.5) 0.6 -0.2 (0.3) 0.0 (0.3) 0.1 (0.1) 0.0 (0.3)
Median (Min, Max) -0.3 (-0.5, 0.5) 0.6 (0.6, 0.6) -0.3 (-0.5, 0.1) 0.0 (-0.3, 0.3) 0.2 (0.0, 0.2) 0.0 (-0.5, 0.6)
95% CI for Median 1 (-0.3, 0.2)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) -0.8 (5.4) 6.1 -2.3 (3.0) -0.0 (2.7) 1.4 (1.2) 0.1 (3.5)
Median (Min, Max) -3.0 (-4.8, 5.3) 6.1 (6.1, 6.1) -2.9 (-4.9, 1.0) 0.0 (-3.2, 3.3) 2.0 (0.0, 2.1) 0.0 (-4.9, 6.1)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
10
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Chloride (mEq/L)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 105.3 (2.1) 103.0 102.0 (3.5) 103.2 (2.3) 101.7 (1.5) 103.1 (2.4)
Median (Min, Max) 106.0 (103.0, 107.0) 103.0 (103.0, 103.0) 104.0 (98.0, 104.0) 104.0 (100.0, 106.0) 102.0 (100.0, 103.0) 103.0 (98.0, 107.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 105.0 (2.6) 102.0 102.7 (1.5) 103.2 (3.1) 103.7 (2.1) 103.5 (2.4)
Median (Min, Max) 104.0 (103.0, 108.0) 102.0 (102.0, 102.0) 103.0 (101.0, 104.0) 103.0 (100.0, 108.0) 103.0 (102.0, 106.0) 103.0 (100.0, 108.0)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) -0.3 (1.5) -1.0 0.7 (4.0) 0.0 (1.2) 2.0 (3.5) 0.4 (2.4)
Median (Min, Max) 0.0 (-2.0, 1.0) -1.0 (-1.0, -1.0) 0.0 (-3.0, 5.0) 0.0 (-1.0, 2.0) 0.0 (0.0, 6.0) 0.0 (-3.0, 6.0)
95% CI for Median 1 (-1.0, 1.0)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) -0.3 (1.4) -1.0 0.7 (4.0) -0.0 (1.2) 2.0 (3.5) 0.4 (2.4)
Median (Min, Max) 0.0 (-1.9, 0.9) -1.0 (-1.0, -1.0) 0.0 (-2.9, 5.1) 0.0 (-1.0, 1.9) 0.0 (0.0, 6.0) 0.0 (-2.9, 6.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
11
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Cholesterol (mg/dL)
Pre-dose value
N 1 1 1 4 3 10
Mean (SD) 72.0 163.0 131.0 177.8 (31.2) 141.3 (127.6) 150.1 (71.0)
Median (Min, Max) 72.0 (72.0, 72.0) 163.0 (163.0, 163.0) 131.0 (131.0, 131.0) 165.5 (156.0, 224.0) 176.0 (0.0, 248.0) 164.0 (0.0, 248.0)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 162.3 (69.5) 155.0 149.0 (21.0) 168.8 (40.2) 178.5 (4.9) 163.6 (37.5)
Median (Min, Max) 162.0 (93.0, 232.0) 155.0 (155.0, 155.0) 158.0 (125.0, 164.0) 163.0 (122.0, 229.0) 178.5 (175.0, 182.0) 162.5 (93.0, 232.0)
Change from Baseline
N 1 1 1 4 2 9
Mean (SD) 21.0 -8.0 -6.0 -12.3 (17.1) 54.5 (170.4) 7.4 (67.5)
Median (Min, Max) 21.0 (21.0, 21.0) -8.0 (-8.0, -8.0) -6.0 (-6.0, -6.0) -10.0 (-34.0, 5.0) 54.5 (-66.0, 175.0) -6.0 (-66.0, 175.0)
95% CI for Median 1 (-34.0, 21.0)
Percentage Change
N 1 1 1 4 1 8
Mean (SD) 29.2 -4.9 -4.6 -7.9 (10.6) -26.6 -4.8 (16.9)
Median (Min, Max) 29.2 (29.2, 29.2) -4.9 (-4.9, -4.9) -4.6 (-4.6, -4.6) -6.1 (-21.8, 2.2) -26.6 (-26.6, -26.6) -4.7 (-26.6, 29.2)
Participant with at least one newly emergent abnormal finding
1 (33.3%) 0 0 0 1 (33.3%) 2 (13.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
12
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Creatinine (mg/dL)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 1.8 (0.6) 1.3 0.7 (0.1) 0.8 (0.2) 0.6 (0.2) 1.0 (0.5)
Median (Min, Max) 2.0 (1.1, 2.3) 1.3 (1.3, 1.3) 0.7 (0.6, 0.8) 0.8 (0.6, 1.0) 0.6 (0.4, 0.8) 0.8 (0.4, 2.3)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 1.6 (0.4) 1.2 0.7 (0.1) 0.8 (0.2) 0.7 (0.2) 1.0 (0.4)
Median (Min, Max) 1.8 (1.1, 1.8) 1.2 (1.2, 1.2) 0.7 (0.6, 0.8) 0.8 (0.7, 1.1) 0.8 (0.5, 0.8) 0.8 (0.5, 1.8)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) -0.2 (0.3) -0.1 0.0 (0.0) 0.0 (0.1) 0.1 (0.1) -0.0 (0.2)
Median (Min, Max) -0.2 (-0.5, 0.0) -0.1 (-0.1, -0.1) 0.0 (0.0, 0.0) 0.1 (-0.1, 0.1) 0.1 (-0.0, 0.2) 0.0 (-0.5, 0.2)
95% CI for Median 1 (-0.1, 0.1)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) -8.6 (12.3) -7.7 4.4 (1.3) 3.8 (8.5) 13.2 (15.7) 2.6 (11.7)
Median (Min, Max) -8.5 (-20.9, 3.8) -7.7 (-7.7, -7.7) 5.1 (2.9, 5.3) 7.8 (-7.2, 13.2) 16.3 (-3.8, 27.1) 3.8 (-20.9, 27.1)
Participant with at least one newly emergent abnormal finding
0 0 0 0 2 (66.7%) 2 (13.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
13
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Glucose (mg/dL)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 79.3 (8.5) 109.0 92.0 (9.6) 96.6 (12.2) 101.3 (11.0) 94.0 (12.7)
Median (Min, Max) 76.0 (73.0, 89.0) 109.0 (109.0, 109.0) 96.0 (81.0, 99.0) 94.0 (84.0, 117.0) 105.0 (89.0, 110.0) 94.0 (73.0, 117.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 85.0 (10.4) 113.0 84.0 (8.7) 92.2 (18.7) 85.0 (3.6) 89.1 (13.6)
Median (Min, Max) 90.0 (73.0, 92.0) 113.0 (113.0, 113.0) 88.0 (74.0, 90.0) 91.0 (74.0, 122.0) 84.0 (82.0, 89.0) 89.0 (73.0, 122.0)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) 5.7 (7.4) 4.0 -8.0 (2.6) -4.4 (23.6) -16.3 (11.5) -4.9 (15.7)
Median (Min, Max) 3.0 (0.0, 14.0) 4.0 (4.0, 4.0) -7.0 (-11.0, -6.0) -2.0 (-38.0, 28.0) -16.0 (-28.0, -5.0) -5.0 (-38.0, 28.0)
95% CI for Median 1 (-11.0, 3.0)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) 7.3 (9.8) 3.7 -8.7 (2.4) -3.4 (22.5) -15.4 (9.9) -4.2 (15.4)
Median (Min, Max) 3.4 (0.0, 18.4) 3.7 (3.7, 3.7) -8.6 (-11.1, -6.3) -2.2 (-32.5, 29.8) -15.2 (-25.5, -5.6) -5.6 (-32.5, 29.8)
Participant with at least one newly emergent abnormal finding
0 1 (100.0%) 0 0 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
14
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Phosphorus (mg/dL)
Pre-dose value
N 2 1 2 4 3 12
Mean (SD) 3.7 (0.1) 4.2 4.7 (0.4) 4.3 (0.7) 4.3 (0.3) 4.3 (0.5)
Median (Min, Max) 3.7 (3.6, 3.7) 4.2 (4.2, 4.2) 4.7 (4.4, 5.0) 4.4 (3.7, 4.9) 4.5 (4.0, 4.5) 4.3 (3.6, 5.0)
Post-dose value
N 0 0 0 0 1 1
Mean (SD) 5.0 5.0
Median (Min, Max) 5.0 (5.0, 5.0) 5.0 (5.0, 5.0)
Change from Baseline
N 0 0 0 0 1 1
Mean (SD) 1.0 1.0
Median (Min, Max) 1.0 (1.0, 1.0) 1.0 (1.0, 1.0)
95% CI for Median 1 (., .)
Percentage Change
N 0 0 0 0 1 1
Mean (SD) 25.0 25.0
Median (Min, Max) 25.0 (25.0, 25.0) 25.0 (25.0, 25.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
15
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Potassium (mEq/L)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 4.8 (0.4) 4.1 4.1 (0.4) 4.3 (0.3) 4.2 (0.8) 4.3 (0.5)
Median (Min, Max) 4.9 (4.3, 5.1) 4.1 (4.1, 4.1) 4.2 (3.6, 4.4) 4.2 (4.0, 4.8) 4.5 (3.3, 4.9) 4.3 (3.3, 5.1)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 5.0 (0.5) 4.3 4.3 (0.5) 3.9 (0.5) 4.5 (0.5) 4.4 (0.6)
Median (Min, Max) 4.8 (4.6, 5.6) 4.3 (4.3, 4.3) 4.3 (3.9, 4.8) 3.6 (3.5, 4.6) 4.6 (4.0, 5.0) 4.3 (3.5, 5.6)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) 0.2 (0.3) 0.2 0.3 (0.2) -0.4 (0.6) 0.3 (0.5) 0.1 (0.5)
Median (Min, Max) 0.3 (-0.1, 0.5) 0.2 (0.2, 0.2) 0.3 (0.1, 0.4) -0.4 (-1.3, 0.4) 0.5 (-0.3, 0.7) 0.2 (-1.3, 0.7)
95% CI for Median 1 (-0.3, 0.4)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) 4.9 (6.2) 4.9 6.6 (3.7) -8.0 (13.3) 8.7 (13.8) 1.7 (11.7)
Median (Min, Max) 7.0 (-2.0, 9.8) 4.9 (4.9, 4.9) 8.3 (2.4, 9.1) -10.0 (-27.1, 9.5) 11.1 (-6.1, 21.2) 4.9 (-27.1, 21.2)
Participant with at least one newly emergent abnormal finding
1 (33.3%) 0 0 0 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
16
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Protein, total (g/d)
Pre-dose value
N 3 1 2 4 3 13
Mean (SD) 7.3 (0.6) 7.2 8.3 (0.1) 7.2 (0.5) 4.4 (3.8) 6.8 (2.1)
Median (Min, Max) 7.2 (6.8, 8.0) 7.2 (7.2, 7.2) 8.3 (8.2, 8.3) 7.1 (6.8, 7.9) 6.4 (0.0, 6.8) 7.2 (0.0, 8.3)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 7.0 (0.9) 6.8 7.3 (0.3) 6.7 (0.7) 6.0 (0.2) 6.8 (0.7)
Median (Min, Max) 6.5 (6.4, 8.0) 6.8 (6.8, 6.8) 7.4 (7.0, 7.5) 6.5 (6.0, 7.5) 6.0 (5.8, 6.1) 6.7 (5.8, 8.0)
Change from Baseline
N 3 1 2 4 2 12
Mean (SD) -0.4 (0.4) -0.4 -0.8 (0.1) -0.7 (0.4) 2.6 (4.6) -0.1 (1.9)
Median (Min, Max) -0.4 (-0.7, 0.0) -0.4 (-0.4, -0.4) -0.8 (-0.9, -0.7) -0.6 (-1.1, -0.3) 2.6 (-0.7, 5.8) -0.6 (-1.1, 5.8)
95% CI for Median 1 (-0.8, -0.3)
Percentage Change
N 3 1 2 4 1 11
Mean (SD) -5.2 (4.9) -5.6 -9.7 (1.6) -9.0 (5.1) -10.3 -7.9 (4.2)
Median (Min, Max) -5.9 (-9.7, 0.0) -5.6 (-5.6, -5.6) -9.7 (-10.8, -8.5) -8.4 (-14.9, -4.4) -10.3 (-10.3, -10.3) -8.5 (-14.9, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 1 (33.3%) 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
17
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Sodium (mEq/L)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 138.7 (1.5) 139.0 139.0 (2.6) 138.4 (2.9) 141.0 (1.0) 139.1 (2.2)
Median (Min, Max) 139.0 (137.0, 140.0) 139.0 (139.0, 139.0) 140.0 (136.0, 141.0) 138.0 (134.0, 141.0) 141.0 (140.0, 142.0) 140.0 (134.0, 142.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 138.3 (1.5) 139.0 137.7 (0.6) 137.8 (3.2) 138.7 (5.1) 138.1 (2.7)
Median (Min, Max) 138.0 (137.0, 140.0) 139.0 (139.0, 139.0) 138.0 (137.0, 138.0) 137.0 (134.0, 142.0) 140.0 (133.0, 143.0) 138.0 (133.0, 143.0)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) -0.3 (1.5) 0.0 -1.3 (3.1) -0.6 (2.4) -2.3 (5.9) -1.0 (3.0)
Median (Min, Max) 0.0 (-2.0, 1.0) 0.0 (0.0, 0.0) -2.0 (-4.0, 2.0) 0.0 (-4.0, 2.0) 0.0 (-9.0, 2.0) 0.0 (-9.0, 2.0)
95% CI for Median 1 (-2.0, 1.0)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) -0.2 (1.1) 0.0 -0.9 (2.2) -0.4 (1.7) -1.6 (4.1) -0.7 (2.1)
Median (Min, Max) 0.0 (-1.4, 0.7) 0.0 (0.0, 0.0) -1.4 (-2.8, 1.5) 0.0 (-2.8, 1.4) 0.0 (-6.3, 1.4) 0.0 (-6.3, 1.5)
Participant with at least one newly emergent abnormal finding
0 0 0 0 1 (33.3%) 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
18
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Calculated eGFR (mL/min per 1.73m²)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 37.5 (12.1) 52.6 90.3 (13.7) 78.1 (12.7) 92.7 (32.0) 73.6 (26.4)
Median (Min, Max) 31.3 (29.6, 51.5) 52.6 (52.6, 52.6) 87.7 (78.1, 105.1) 74.8 (63.6, 98.2) 99.7 (57.9, 120.6) 74.8 (29.6, 120.6)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 40.4 (8.1) 57.0 86.4 (12.2) 78.2 (17.4) 92.9 (42.0) 73.8 (27.3)
Median (Min, Max) 37.5 (34.3, 49.6) 57.0 (57.0, 57.0) 83.5 (75.9, 99.8) 76.5 (59.0, 103.3) 78.4 (60.1, 140.2) 75.9 (34.3, 140.2)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) 3.0 (4.8) 4.4 -3.9 (1.6) 0.1 (6.5) 0.2 (20.5) 0.2 (9.1)
Median (Min, Max) 2.9 (-1.9, 7.8) 4.4 (4.4, 4.4) -4.3 (-5.3, -2.2) 2.3 (-8.7, 6.2) 2.3 (-21.3, 19.6) 2.3 (-21.3, 19.6)
95% CI for Median 1 (-4.6, 5.2)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) 10.7 (15.1) 8.3 -4.2 (1.2) -0.6 (8.4) -0.4 (19.1) 1.6 (11.7)
Median (Min, Max) 9.3 (-3.6, 26.4) 8.3 (8.3, 8.3) -4.9 (-5.0, -2.8) 3.0 (-11.7, 7.8) 3.9 (-21.3, 16.2) 3.0 (-21.3, 26.4)
Participant with at least one newly emergent abnormal finding
0 0 0 0 2 (66.7%) 2 (13.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Albumin (g/dL)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 4.5 (0.2) 4.2 (0.0) 4.5 (0.3) 4.4 (0.3) 4.4 (0.3)
Median (Min, Max) 4.5 (4.3, 4.6) 4.2 (4.2, 4.2) 4.5 (4.0, 4.9) 4.4 (4.2, 4.6) 4.5 (4.0, 4.9)
Post-dose value
N 2 2 4 1 9
Mean (SD) 4.4 (0.1) 3.8 (0.3) 4.5 (0.1) 4.4 4.3 (0.3)
Median (Min, Max) 4.4 (4.3, 4.4) 3.8 (3.6, 4.0) 4.6 (4.3, 4.6) 4.4 (4.4, 4.4) 4.4 (3.6, 4.6)
Change from Baseline
N 2 2 4 1 9
Mean (SD) -0.1 (0.1) -0.4 (0.3) 0.0 (0.4) -0.2 -0.1 (0.3)
Median (Min, Max) -0.1 (-0.2, 0.0) -0.4 (-0.6, -0.2) -0.2 (-0.3, 0.6) -0.2 (-0.2, -0.2) -0.2 (-0.6, 0.6)
95% CI for Median 1 (-0.3, 0.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) -2.2 (3.1) -9.5 (6.7) 0.6 (9.8) -4.4 -2.8 (7.7)
Median (Min, Max) -2.2 (-4.3, 0.0) -9.5 (-14.3, -4.8) -3.3 (-6.1, 15.0) -4.4 (-4.3, -4.3) -4.4 (-14.3, 15.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Alkaline phosphatase (U/L)
Pre-dose value
N 2 1 5 2 10
Mean (SD) 181.0 (89.1) 142.0 136.8 (38.4) 221.0 (8.5) 163.0 (52.9)
Median (Min, Max) 181.0 (118.0, 244.0) 142.0 (142.0, 142.0) 123.0 (96.0, 193.0) 221.0 (215.0, 227.0) 149.5 (96.0, 244.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 172.0 (93.3) 240.5 (164.8) 135.3 (32.2) 198.0 173.8 (82.5)
Median (Min, Max) 172.0 (106.0, 238.0) 240.5 (124.0, 357.0) 130.5 (107.0, 173.0) 198.0 (198.0, 198.0) 151.0 (106.0, 357.0)
Change from Baseline
N 2 1 4 1 8
Mean (SD) -9.0 (4.2) -18.0 -7.0 (13.3) -29.0 -11.6 (11.9)
Median (Min, Max) -9.0 (-12.0, -6.0) -18.0 (-18.0, -18.0) -9.5 (-20.0, 11.0) -29.0 (-29.0, -29.0) -12.5 (-29.0, 11.0)
95% CI for Median 1 (-20.0, 11.0)
Percentage Change
N 2 1 4 1 8
Mean (SD) -6.3 (5.5) -12.7 -3.3 (10.3) -12.8 -6.4 (8.2)
Median (Min, Max) -6.3 (-10.2, -2.5) -12.7 (-12.7, -12.7) -7.1 (-10.6, 11.5) -12.8 (-12.8, -12.8) -10.3 (-12.8, 11.5)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
ALT (U/L)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 23.5 (13.4) 25.0 (26.9) 20.8 (8.9) 21.5 (12.0) 22.2 (11.8)
Median (Min, Max) 23.5 (14.0, 33.0) 25.0 (6.0, 44.0) 20.0 (10.0, 32.0) 21.5 (13.0, 30.0) 20.0 (6.0, 44.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 25.0 (17.0) 21.5 (20.5) 13.5 (3.8) 9.0 17.3 (11.4)
Median (Min, Max) 25.0 (13.0, 37.0) 21.5 (7.0, 36.0) 15.0 (8.0, 16.0) 9.0 (9.0, 9.0) 14.0 (7.0, 37.0)
Change from Baseline
N 2 2 4 1 9
Mean (SD) 1.5 (3.5) -3.5 (6.4) -4.5 (6.0) -4.0 -2.9 (5.2)
Median (Min, Max) 1.5 (-1.0, 4.0) -3.5 (-8.0, 1.0) -3.0 (-13.0, 1.0) -4.0 (-4.0, -4.0) -2.0 (-13.0, 4.0)
95% CI for Median 1 (-8.0, 1.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) 2.5 (13.6) -0.8 (24.6) -20.4 (22.4) -30.8 -12.1 (21.2)
Median (Min, Max) 2.5 (-7.1, 12.1) -0.8 (-18.2, 16.7) -20.0 (-48.1, 6.7) -30.8 (-30.8, -30.8) -18.2 (-48.1, 16.7)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
AST (U/L)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 20.0 (7.1) 34.5 (23.3) 21.2 (7.9) 30.0 (4.2) 25.0 (11.0)
Median (Min, Max) 20.0 (15.0, 25.0) 34.5 (18.0, 51.0) 23.0 (13.0, 32.0) 30.0 (27.0, 33.0) 24.0 (13.0, 51.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 23.0 (7.1) 38.5 (6.4) 16.8 (4.5) 25.0 23.9 (9.9)
Median (Min, Max) 23.0 (18.0, 28.0) 38.5 (34.0, 43.0) 15.5 (13.0, 23.0) 25.0 (25.0, 25.0) 23.0 (13.0, 43.0)
Change from Baseline
N 2 2 4 1 9
Mean (SD) 3.0 (0.0) 4.0 (17.0) -1.8 (5.1) -2.0 0.6 (7.3)
Median (Min, Max) 3.0 (3.0, 3.0) 4.0 (-8.0, 16.0) -0.5 (-9.0, 3.0) -2.0 (-2.0, -2.0) 0.0 (-9.0, 16.0)
95% CI for Median 1 (-8.0, 3.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) 16.0 (5.7) 36.6 (73.9) -5.5 (25.1) -7.4 8.4 (35.6)
Median (Min, Max) 16.0 (12.0, 20.0) 36.6 (-15.7, 88.9) -2.1 (-39.1, 21.4) -7.4 (-7.4, -7.4) 0.0 (-39.1, 88.9)
Participant with at least one newly emergent abnormal finding
0 1 (50.0%) 0 0 1 (9.1%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
5
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Bicarbonate (mEq/L)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 19.0 (0.0) 19.5 (3.5) 23.6 (1.1) 24.5 (3.5) 22.2 (2.9)
Median (Min, Max) 19.0 (19.0, 19.0) 19.5 (17.0, 22.0) 24.0 (22.0, 25.0) 24.5 (22.0, 27.0) 22.0 (17.0, 27.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 18.0 (5.7) 19.0 (1.4) 21.0 (3.2) 20.0 19.8 (3.1)
Median (Min, Max) 18.0 (14.0, 22.0) 19.0 (18.0, 20.0) 20.5 (18.0, 25.0) 20.0 (20.0, 20.0) 20.0 (14.0, 25.0)
Change from Baseline
N 2 2 4 1 9
Mean (SD) -1.0 (5.7) -0.5 (2.1) -2.5 (3.4) -2.0 -1.7 (3.1)
Median (Min, Max) -1.0 (-5.0, 3.0) -0.5 (-2.0, 1.0) -3.0 (-6.0, 2.0) -2.0 (-2.0, -2.0) -2.0 (-6.0, 3.0)
95% CI for Median 1 (-5.0, 2.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) -5.3 (29.8) -1.6 (10.6) -10.5 (14.3) -9.1 -7.2 (14.7)
Median (Min, Max) -5.3 (-26.3, 15.8) -1.6 (-9.1, 5.9) -13.3 (-24.0, 8.7) -9.1 (-9.1, -9.1) -9.1 (-26.3, 15.8)
Participant with at least one newly emergent abnormal finding
1 (50.0%) 0 2 (40.0%) 0 3 (27.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
6
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Bilirubin, direct (mg/dL)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 0.2 (0.0) 0.1 (0.1) 0.1 (0.1) 0.2 (0.0) 0.2 (0.1)
Median (Min, Max) 0.2 (0.2, 0.2) 0.1 (0.0, 0.2) 0.2 (0.0, 0.2) 0.2 (0.2, 0.2) 0.2 (0.0, 0.2)
Post-dose value
N 2 2 4 1 9
Mean (SD) 0.2 (0.0) 0.2 (0.0) 0.2 (0.0) 0.2 0.2 (0.0)
Median (Min, Max) 0.2 (0.2, 0.2) 0.2 (0.2, 0.2) 0.2 (0.2, 0.2) 0.2 (0.2, 0.2) 0.2 (0.2, 0.2)
Change from Baseline
N 2 2 4 1 9
Mean (SD) 0.0 (0.0) 0.1 (0.1) 0.1 (0.1) 0.0 0.0 (0.1)
Median (Min, Max) 0.0 (0.0, 0.0) 0.1 (0.0, 0.2) 0.0 (0.0, 0.2) 0.0 (0.0, 0.0) 0.0 (0.0, 0.2)
95% CI for Median 1 (0.0, 0.2)
Percentage Change
N 2 1 3 1 7
Mean (SD) 0.0 (0.0) 0.0 0.0 (0.0) 0.0 0.0 (0.0)
Median (Min, Max) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0) 0.0 (0.0, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
7
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Bilirubin, total (mg/dL)
Pre-dose value
N 2 1 5 2 10
Mean (SD) 0.2 (0.0) 0.1 0.2 (0.1) 0.1 (0.0) 0.2 (0.1)
Median (Min, Max) 0.2 (0.2, 0.2) 0.1 (0.1, 0.1) 0.2 (0.1, 0.3) 0.1 (0.1, 0.1) 0.2 (0.1, 0.3)
Post-dose value
N 2 2 4 1 9
Mean (SD) 0.3 (0.2) 0.2 (0.1) 0.2 (0.1) 0.1 0.2 (0.1)
Median (Min, Max) 0.3 (0.1, 0.4) 0.2 (0.1, 0.2) 0.2 (0.1, 0.2) 0.1 (0.1, 0.1) 0.1 (0.1, 0.4)
Change from Baseline
N 2 1 4 1 8
Mean (SD) 0.1 (0.2) 0.1 -0.1 (0.1) 0.0 -0.0 (0.1)
Median (Min, Max) 0.1 (-0.1, 0.2) 0.1 (0.1, 0.1) -0.1 (-0.2, 0.0) 0.0 (0.0, 0.0) 0.0 (-0.2, 0.2)
95% CI for Median 1 (-0.1, 0.2)
Percentage Change
N 2 1 4 1 8
Mean (SD) 25.0 (106.1) 100.0 -25.0 (31.9) 0.0 6.3 (63.0)
Median (Min, Max) 25.0 (-50.0, 100.0) 100.0 (100.0, 100.0) -16.7 (-66.7, 0.0) 0.0 (0.0, 0.0) 0.0 (-66.7, 100.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
8
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Blood urea nitrogen (BUN) (mg/dL)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 26.5 (6.4) 26.0 (7.1) 15.4 (3.0) 29.5 (4.9) 21.9 (7.4)
Median (Min, Max) 26.5 (22.0, 31.0) 26.0 (21.0, 31.0) 15.0 (12.0, 19.0) 29.5 (26.0, 33.0) 21.0 (12.0, 33.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 30.0 (11.3) 25.0 (12.7) 16.3 (3.4) 26.0 22.3 (8.8)
Median (Min, Max) 30.0 (22.0, 38.0) 25.0 (16.0, 34.0) 15.5 (13.0, 21.0) 26.0 (26.0, 26.0) 21.0 (13.0, 38.0)
Change from Baseline
N 2 2 4 1 9
Mean (SD) 3.5 (4.9) -1.0 (5.7) 0.8 (4.6) -7.0 0.1 (5.0)
Median (Min, Max) 3.5 (0.0, 7.0) -1.0 (-5.0, 3.0) 2.5 (-6.0, 4.0) -7.0 (-7.0, -7.0) 2.0 (-7.0, 7.0)
95% CI for Median 1 (-6.0, 4.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) 11.3 (16.0) -7.1 (23.7) 8.5 (27.9) -21.2 2.3 (22.9)
Median (Min, Max) 11.3 (0.0, 22.6) -7.1 (-23.8, 9.7) 16.0 (-31.6, 33.3) -21.2 (-21.2, -21.2) 9.7 (-31.6, 33.3)
Participant with at least one newly emergent abnormal finding
2 (100.0%) 1 (50.0%) 1 (20.0%) 0 4 (36.4%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
9
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Calcium (mg/dL)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 9.7 (0.0) 9.6 (0.1) 9.9 (0.8) 10.0 (0.6) 9.8 (0.5)
Median (Min, Max) 9.7 (9.7, 9.7) 9.6 (9.5, 9.7) 9.8 (9.1, 11.0) 10.0 (9.5, 10.4) 9.7 (9.1, 11.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 9.5 (0.0) 9.5 (0.1) 9.8 (0.1) 9.9 9.7 (0.2)
Median (Min, Max) 9.5 (9.5, 9.5) 9.5 (9.4, 9.5) 9.8 (9.6, 9.9) 9.9 (9.9, 9.9) 9.6 (9.4, 9.9)
Change from Baseline
N 2 2 4 1 9
Mean (SD) -0.2 (0.0) -0.2 (0.1) -0.3 (0.7) -0.5 -0.3 (0.4)
Median (Min, Max) -0.2 (-0.2, -0.2) -0.2 (-0.2, -0.1) -0.4 (-1.1, 0.5) -0.5 (-0.5, -0.5) -0.2 (-1.1, 0.5)
95% CI for Median 1 (-0.5, -0.1)
Percentage Change
N 2 2 4 1 9
Mean (SD) -2.1 (0.0) -1.6 (0.7) -2.9 (6.4) -4.8 -2.6 (4.1)
Median (Min, Max) -2.1 (-2.1, -2.1) -1.6 (-2.1, -1.1) -3.5 (-10.0, 5.4) -4.8 (-4.8, -4.8) -2.1 (-10.0, 5.4)
Participant with at least one newly emergent abnormal finding
0 0 1 (20.0%) 0 1 (9.1%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
10
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Chloride (mEq/L)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 106.0 (1.4) 108.0 (2.8) 102.8 (2.4) 104.5 (4.9) 104.6 (3.2)
Median (Min, Max) 106.0 (105.0, 107.0) 108.0 (106.0, 110.0) 103.0 (100.0, 106.0) 104.5 (101.0, 108.0) 105.0 (100.0, 110.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 106.5 (0.7) 104.5 (0.7) 102.0 (2.9) 105.0 103.9 (2.7)
Median (Min, Max) 106.5 (106.0, 107.0) 104.5 (104.0, 105.0) 102.0 (99.0, 105.0) 105.0 (105.0, 105.0) 105.0 (99.0, 107.0)
Change from Baseline
N 2 2 4 1 9
Mean (SD) 0.5 (2.1) -3.5 (2.1) 0.0 (3.4) -3.0 -1.0 (2.9)
Median (Min, Max) 0.5 (-1.0, 2.0) -3.5 (-5.0, -2.0) 0.0 (-4.0, 4.0) -3.0 (-3.0, -3.0) -1.0 (-5.0, 4.0)
95% CI for Median 1 (-4.0, 2.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) 0.5 (2.0) -3.2 (1.9) 0.0 (3.3) -2.8 -0.9 (2.8)
Median (Min, Max) 0.5 (-0.9, 1.9) -3.2 (-4.5, -1.9) -0.0 (-3.9, 4.0) -2.8 (-2.8, -2.8) -1.0 (-4.5, 4.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
11
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Cholesterol (mg/dL)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 153.5 (14.8) 166.0 (19.8) 190.4 (22.6) 140.0 (55.2) 170.1 (31.9)
Median (Min, Max) 153.5 (143.0, 164.0) 166.0 (152.0, 180.0) 190.0 (165.0, 213.0) 140.0 (101.0, 179.0) 171.0 (101.0, 213.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 151.0 (14.1) 146.0 (9.9) 169.0 (22.7) 137.0 156.3 (19.8)
Median (Min, Max) 151.0 (141.0, 161.0) 146.0 (139.0, 153.0) 168.0 (146.0, 194.0) 137.0 (137.0, 137.0) 153.0 (137.0, 194.0)
Change from Baseline
N 2 2 4 1 9
Mean (SD) -2.5 (0.7) -20.0 (29.7) -21.5 (28.7) -42.0 -19.2 (23.6)
Median (Min, Max) -2.5 (-3.0, -2.0) -20.0 (-41.0, 1.0) -19.0 (-59.0, 11.0) -42.0 (-42.0, -42.0) -19.0 (-59.0, 11.0)
95% CI for Median 1 (-42.0, 1.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) -1.6 (0.3) -11.1 (16.6) -10.4 (14.0) -23.5 -10.1 (12.2)
Median (Min, Max) -1.6 (-1.8, -1.4) -11.1 (-22.8, 0.7) -10.2 (-27.7, 6.4) -23.5 (-23.5, -23.5) -8.9 (-27.7, 6.4)
Participant with at least one newly emergent abnormal finding
0 0 1 (20.0%) 0 1 (9.1%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
12
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Creatinine (mg/dL)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 1.5 (0.5) 1.5 (1.0) 0.8 (0.3) 0.9 (0.2) 1.1 (0.5)
Median (Min, Max) 1.5 (1.1, 1.8) 1.5 (0.8, 2.2) 0.7 (0.4, 1.2) 0.9 (0.8, 1.1) 1.0 (0.4, 2.2)
Post-dose value
N 2 2 4 1 9
Mean (SD) 1.5 (0.5) 1.5 (0.9) 0.9 (0.3) 0.6 1.2 (0.6)
Median (Min, Max) 1.5 (1.2, 1.9) 1.5 (0.8, 2.1) 0.9 (0.6, 1.4) 0.6 (0.6, 0.6) 1.0 (0.6, 2.1)
Change from Baseline
N 2 2 4 1 9
Mean (SD) 0.1 (0.1) -0.0 (0.1) 0.0 (0.1) -0.1 0.0 (0.1)
Median (Min, Max) 0.1 (0.0, 0.1) -0.0 (-0.1, 0.0) 0.0 (-0.1, 0.2) -0.1 (-0.1, -0.1) 0.0 (-0.1, 0.2)
95% CI for Median 1 (-0.1, 0.1)
Percentage Change
N 2 2 4 1 9
Mean (SD) 3.6 (2.6) 0.8 (6.2) 3.7 (14.0) -14.7 1.0 (10.7)
Median (Min, Max) 3.6 (1.8, 5.5) 0.8 (-3.6, 5.2) 5.1 (-12.1, 16.7) -14.7 (-14.7, -14.7) 1.8 (-14.7, 16.7)
Participant with at least one newly emergent abnormal finding
1 (50.0%) 1 (50.0%) 2 (40.0%) 0 4 (36.4%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
13
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Glucose (mg/dL)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 101.0 (22.6) 99.0 (11.3) 111.8 (30.1) 90.5 (6.4) 103.6 (22.5)
Median (Min, Max) 101.0 (85.0, 117.0) 99.0 (91.0, 107.0) 94.0 (88.0, 155.0) 90.5 (86.0, 95.0) 94.0 (85.0, 155.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 95.5 (6.4) 86.5 (4.9) 151.5 (117.8) 82.0 116.9 (79.4)
Median (Min, Max) 95.5 (91.0, 100.0) 86.5 (83.0, 90.0) 94.5 (89.0, 328.0) 82.0 (82.0, 82.0) 90.0 (82.0, 328.0)
Change from Baseline
N 2 2 4 1 9
Mean (SD) -5.5 (16.3) -12.5 (16.3) 34.3 (95.1) -13.0 9.8 (63.3)
Median (Min, Max) -5.5 (-17.0, 6.0) -12.5 (-24.0, -1.0) 3.5 (-43.0, 173.0) -13.0 (-13.0, -13.0) -1.0 (-43.0, 173.0)
95% CI for Median 1 (-24.0, 6.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) -3.7 (15.3) -11.8 (15.1) 21.7 (62.4) -13.7 4.7 (42.3)
Median (Min, Max) -3.7 (-14.5, 7.1) -11.8 (-22.4, -1.1) 3.8 (-32.6, 111.6) -13.7 (-13.7, -13.7) -1.1 (-32.6, 111.6)
Participant with at least one newly emergent abnormal finding
1 (50.0%) 0 0 0 1 (9.1%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
14
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Phosphorus (mg/dL)
Pre-dose value
N 1 1 3 1 6
Mean (SD) 3.5 5.9 3.8 (0.3) 4.7 4.3 (0.9)
Median (Min, Max) 3.5 (3.5, 3.5) 5.9 (5.9, 5.9) 4.0 (3.4, 4.0) 4.7 (4.7, 4.7) 4.0 (3.4, 5.9)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
15
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Potassium (mEq/L)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 4.8 (0.6) 5.1 (1.1) 4.1 (0.6) 5.2 (0.9) 4.6 (0.8)
Median (Min, Max) 4.8 (4.4, 5.2) 5.1 (4.3, 5.9) 3.8 (3.6, 5.0) 5.2 (4.5, 5.8) 4.4 (3.6, 5.9)
Post-dose value
N 2 2 4 1 9
Mean (SD) 4.4 (0.4) 5.0 (0.4) 4.0 (0.5) 4.5 4.4 (0.5)
Median (Min, Max) 4.4 (4.1, 4.7) 5.0 (4.7, 5.2) 4.2 (3.3, 4.4) 4.5 (4.5, 4.5) 4.4 (3.3, 5.2)
Change from Baseline
N 2 2 4 1 9
Mean (SD) -0.4 (0.1) -0.2 (1.5) -0.2 (0.8) -1.3 -0.3 (0.8)
Median (Min, Max) -0.4 (-0.5, -0.3) -0.2 (-1.2, 0.9) -0.2 (-0.9, 0.6) -1.3 (-1.3, -1.3) -0.5 (-1.3, 0.9)
95% CI for Median 1 (-1.2, 0.6)
Percentage Change
N 2 2 4 1 9
Mean (SD) -8.2 (2.0) 0.3 (29.2) -2.5 (19.9) -22.4 -5.4 (17.5)
Median (Min, Max) -8.2 (-9.6, -6.8) 0.3 (-20.3, 20.9) -2.2 (-21.4, 15.8) -22.4 (-22.4, -22.4) -9.6 (-22.4, 20.9)
Participant with at least one newly emergent abnormal finding
0 0 1 (20.0%) 0 1 (9.1%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
16
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Protein, total (g/d)
Pre-dose value
N 2 1 5 2 10
Mean (SD) 7.3 (0.1) 7.0 7.2 (0.7) 7.9 (1.7) 7.3 (0.8)
Median (Min, Max) 7.3 (7.2, 7.4) 7.0 (7.0, 7.0) 7.1 (6.4, 8.3) 7.9 (6.7, 9.1) 7.2 (6.4, 9.1)
Post-dose value
N 2 2 4 1 9
Mean (SD) 7.0 (0.1) 6.4 (0.4) 6.8 (0.5) 8.4 6.9 (0.7)
Median (Min, Max) 7.0 (6.9, 7.1) 6.4 (6.1, 6.7) 6.7 (6.4, 7.5) 8.4 (8.4, 8.4) 6.8 (6.1, 8.4)
Change from Baseline
N 2 1 4 1 8
Mean (SD) -0.3 (0.0) -0.3 -0.4 (0.3) -0.7 -0.4 (0.3)
Median (Min, Max) -0.3 (-0.3, -0.3) -0.3 (-0.3, -0.3) -0.3 (-0.8, 0.0) -0.7 (-0.7, -0.7) -0.3 (-0.8, 0.0)
95% CI for Median 1 (-0.7, 0.0)
Percentage Change
N 2 1 4 1 8
Mean (SD) -4.1 (0.1) -4.3 -4.6 (3.9) -7.7 -4.8 (2.8)
Median (Min, Max) -4.1 (-4.2, -4.1) -4.3 (-4.3, -4.3) -4.3 (-9.6, 0.0) -7.7 (-7.7, -7.7) -4.3 (-9.6, 0.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
17
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Sodium (mEq/L)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 138.5 (0.7) 140.5 (2.1) 140.0 (2.7) 137.5 (2.1) 139.4 (2.3)
Median (Min, Max) 138.5 (138.0, 139.0) 140.5 (139.0, 142.0) 140.0 (137.0, 144.0) 137.5 (136.0, 139.0) 139.0 (136.0, 144.0)
Post-dose value
N 2 2 4 1 9
Mean (SD) 138.0 (2.8) 138.0 (2.8) 136.5 (3.3) 136.0 137.1 (2.6)
Median (Min, Max) 138.0 (136.0, 140.0) 138.0 (136.0, 140.0) 137.0 (132.0, 140.0) 136.0 (136.0, 136.0) 137.0 (132.0, 140.0)
Change from Baseline
N 2 2 4 1 9
Mean (SD) -0.5 (3.5) -2.5 (4.9) -2.5 (2.4) 0.0 -1.8 (2.8)
Median (Min, Max) -0.5 (-3.0, 2.0) -2.5 (-6.0, 1.0) -2.5 (-5.0, 0.0) 0.0 (0.0, 0.0) -1.0 (-6.0, 2.0)
95% CI for Median 1 (-5.0, 1.0)
Percentage Change
N 2 2 4 1 9
Mean (SD) -0.4 (2.6) -1.8 (3.5) -1.8 (1.7) 0.0 -1.3 (2.0)
Median (Min, Max) -0.4 (-2.2, 1.4) -1.8 (-4.2, 0.7) -1.8 (-3.6, 0.0) 0.0 (0.0, 0.0) -0.7 (-4.2, 1.4)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.3.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Chemistry
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
18
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Calculated eGFR (mL/min per 1.73m²)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 45.2 (9.1) 40.6 (16.1) 84.2 (20.5) 65.0 (6.3) 65.7 (24.2)
Median (Min, Max) 45.2 (38.8, 51.6) 40.6 (29.2, 52.0) 87.4 (62.5, 111.2) 65.0 (60.5, 69.4) 62.5 (29.2, 111.2)
Post-dose value
N 2 2 4 1 9
Mean (SD) 43.7 (9.9) 39.9 (13.5) 76.3 (22.5) 81.3 61.5 (24.0)
Median (Min, Max) 43.7 (36.7, 50.7) 39.9 (30.3, 49.5) 71.4 (54.7, 107.5) 81.3 (81.3, 81.3) 54.7 (30.3, 107.5)
Change from Baseline
N 2 2 4 1 9
Mean (SD) -1.5 (0.8) -0.7 (2.6) -1.1 (11.4) 11.9 0.3 (8.3)
Median (Min, Max) -1.5 (-2.0, -0.9) -0.7 (-2.6, 1.1) -2.5 (-12.5, 13.0) 11.9 (11.9, 11.9) -0.9 (-12.5, 13.0)
95% CI for Median 1 (-7.8, 11.9)
Percentage Change
N 2 2 4 1 9
Mean (SD) -3.5 (2.5) -0.6 (6.2) -2.2 (13.5) 17.2 0.0 (10.8)
Median (Min, Max) -3.5 (-5.2, -1.7) -0.6 (-4.9, 3.8) -4.2 (-14.3, 13.8) 17.2 (17.2, 17.2) -1.7 (-14.3, 17.2)
Participant with at least one newly emergent abnormal finding
1 (50.0%) 1 (50.0%) 2 (40.0%) 0 4 (36.4%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Urine creatinine
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 50.8 (4.3) 205.9 128.0 (36.4) 130.8 (46.8) 58.4 (16.8) 104.8 (55.0)
Median (Min, Max) 49.2 (47.6, 55.7) 205.9 (205.9, 205.9) 120.4 (96.1, 167.6) 107.4 (89.5, 205.2) 56.0 (43.0, 76.3) 96.1 (43.0, 205.9)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 54.5 (9.4) 254.6 151.4 (49.1) 127.5 (44.6) 60.1 (12.7) 116.4 (64.6)
Median (Min, Max) 53.8 (45.5, 64.2) 254.6 (254.6, 254.6) 127.1 (119.3, 207.9) 102.5 (88.1, 180.2) 60.1 (51.1, 69.1) 98.8 (45.5, 254.6)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) 3.7 (9.8) 48.7 23.4 (16.8) -3.3 (68.9) -6.1 (27.1) 7.2 (42.9)
Median (Min, Max) -1.9 (-2.1, 15.0) 48.7 (48.7, 48.7) 23.2 (6.7, 40.3) 13.0 (-110.2, 75.9) -6.1 (-25.2, 13.1) 13.1 (-110.2, 75.9)
95% CI for Median 1 (-2.1, 40.3)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) 7.6 (19.9) 23.7 17.9 (10.7) 6.4 (46.8) -4.8 (39.9) 8.7 (30.7)
Median (Min, Max) -3.4 (-4.4, 30.5) 23.7 (23.7, 23.7) 24.1 (5.6, 24.1) 14.5 (-53.7, 72.8) -4.8 (-33.0, 23.4) 15.4 (-53.7, 72.8)
Participant with at least one newly emergent abnormal finding
0 1 (100.0%) 0 0 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Microalbuminuria
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 651.9 (640.7) 4.0 73.7 (109.3) 86.4 (80.5) 496.0 (830.8) 273.4 (477.8)
Median (Min, Max) 631.0 (21.9, 1302.8) 4.0 (4.0, 4.0) 14.9 (6.4, 199.9) 96.1 (5.5, 189.9) 18.8 (14.0, 1455.3) 21.9 (4.0, 1455.3)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 408.8 (399.7) 4.0 16.4 (16.1) 34.9 (23.1) 154.4 (184.1) 125.9 (230.4)
Median (Min, Max) 373.5 (27.9, 824.9) 4.0 (4.0, 4.0) 8.1 (6.2, 35.0) 22.2 (13.6, 61.2) 154.4 (24.2, 284.6) 26.1 (4.0, 824.9)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) -243.1 (242.3) 0.0 -57.3 (93.3) -51.6 (68.3) -580.3 (835.0) -165.7 (321.1)
Median (Min, Max) -257.5 (-477.9, 6.0) 0.0 (0.0, 0.0) -8.7 (-164.9, 1.7) -34.9 (-131.1, 16.7) -580.3 (-1171, 10.2) -21.8 (-1171, 16.7)
95% CI for Median 1 (-165, 6.6)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) -16.7 (38.2) 0.0 -38.1 (57.3) 41.3 (162.8) -3.8 (108.4) 2.5 (104.1)
Median (Min, Max) -36.7 (-40.8, 27.4) 0.0 (0.0, 0.0) -58.4 (-82.5, 26.6) -36.3 (-86.1, 303.6) -3.8 (-80.4, 72.9) -36.5 (-86.1, 303.6)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 1 (33.3%) 2 (13.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Protein
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 101.6 (79.8) 22.3 34.0 (24.7) 34.1 (19.5) 82.4 (125.1) 56.4 (65.5)
Median (Min, Max) 107.6 (18.9, 178.2) 22.3 (22.3, 22.3) 28.1 (12.8, 61.2) 29.6 (10.7, 59.7) 12.0 (8.3, 226.8) 28.1 (8.3, 226.8)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 66.9 (46.5) 21.4 26.3 (14.9) 21.7 (10.3) 40.0 (34.3) 35.0 (28.8)
Median (Min, Max) 66.7 (20.5, 113.5) 21.4 (21.4, 21.4) 21.3 (14.5, 43.0) 21.5 (9.6, 32.9) 40.0 (15.7, 64.2) 21.5 (9.6, 113.5)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) -34.7 (33.6) -0.9 -7.8 (28.6) -12.3 (16.5) -79.5 (117.6) -24.9 (45.8)
Median (Min, Max) -40.9 (-64.7, 1.6) -0.9 (-0.9, -0.9) 1.7 (-39.9, 14.9) -16.1 (-28.6, 10.0) -79.5 (-162.6, 3.7) -8.6 (-162.6, 14.9)
95% CI for Median 1 (-39.9, 3.7)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) -22.0 (26.4) -4.0 0.4 (60.2) -24.7 (42.4) -20.4 (72.5) -16.7 (41.6)
Median (Min, Max) -36.3 (-38.0, 8.5) -4.0 (-4.0, -4.0) 13.3 (-65.2, 53.0) -47.9 (-54.6, 43.7) -20.4 (-71.7, 30.8) -23.3 (-71.7, 53.0)
Participant with at least one newly emergent abnormal finding
0 0 1 (33.3%) 1 (20.0%) 1 (33.3%) 3 (20.0%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Albumin/creatinine ratio
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 1353.0 (1350.4) 2.0 60.7 (91.2) 79.6 (89.3) 658.6 (1081.2) 441.1 (843.1)
Median (Min, Max) 1283.0 (39.0, 2737.0) 2.0 (2.0, 2.0) 9.0 (7.0, 166.0) 47.0 (4.0, 212.0) 44.0 (24.9, 1907.0) 44.0 (2.0, 2737.0)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 815.7 (903.5) 2.0 12.7 (13.4) 31.8 (26.4) 296.0 (369.1) 231.3 (496.1)
Median (Min, Max) 582.0 (52.0, 1813.0) 2.0 (2.0, 2.0) 7.0 (3.0, 28.0) 15.0 (10.0, 64.0) 296.0 (35.0, 557.0) 31.5 (2.0, 1813.0)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) -537.3 (489.5) 0.0 -48.0 (78.0) -47.8 (82.1) -670.0 (961.7) -238.2 (432.4)
Median (Min, Max) -701.0 (-924.0, 13.0) 0.0 (0.0, 0.0) -6.0 (-138.0, 0.0) 8.0 (-155.0, 17.0) -670.0 (-1350, 10.1) -3.0 (-1350, 17.0)
95% CI for Median 1 (-155, 10.1)
Percentage Change
N 3 1 3 5 2 14
Mean (SD) -18.4 (46.0) 0.0 -49.9 (44.0) 42.0 (132.3) -15.1 (78.7) -1.8 (88.6)
Median (Min, Max) -33.8 (-54.6, 33.3) 0.0 (0.0, 0.0) -66.7 (-83.1, 0.0) 36.2 (-92.2, 225.0) -15.1 (-70.8, 40.6) -16.9 (-92.2, 225.0)
Participant with at least one newly emergent abnormal finding
0 0 0 1 (20.0%) 1 (33.3%) 2 (13.3%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC1
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Percentage change not calculated when pre-dose value equals to 0.
5
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Protein/creatinine ratio
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 2.1 (1.7) 0.1 0.3 (0.2) 0.3 (0.2) 1.1 (1.7) 0.8 (1.2)
Median (Min, Max) 2.2 (0.3, 3.7) 0.1 (0.1, 0.1) 0.2 (0.1, 0.5) 0.3 (0.1, 0.5) 0.2 (0.0, 3.0) 0.3 (0.0, 3.7)
Post-dose value
N 3 1 3 5 2 14
Mean (SD) 1.3 (1.1) 0.1 0.2 (0.0) 0.2 (0.1) 0.8 (0.7) 0.5 (0.7)
Median (Min, Max) 1.0 (0.4, 2.5) 0.1 (0.1, 0.1) 0.2 (0.1, 0.2) 0.2 (0.1, 0.3) 0.8 (0.2, 1.3) 0.2 (0.1, 2.5)
Change from Baseline
N 3 1 3 5 2 14
Mean (SD) -0.8 (0.7) -0.0 -0.1 (0.2) -0.1 (0.2) -0.7 (1.4) -0.3 (0.6)
Median (Min, Max) -1.2 (-1.3, 0.0) -0.0 (-0.0, -0.0) -0.0 (-0.3, 0.0) 0.0 (-0.3, 0.0) -0.7 (-1.7, 0.2) -0.0 (-1.7, 0.2)
95% CI for Median 1 (-0.3, 0.0)
Percentage Change
N 3 1 3 5 1 13
Mean (SD) -24.7 (33.0) -27.3 -16.9 (45.8) -18.6 (45.2) -57.6 -23.3 (36.5)
Median (Min, Max) -33.4 (-52.5, 11.8) -27.3 (-27.3, -27.3) -7.7 (-66.7, 23.5) 10.0 (-75.0, 18.8) -57.6 (-57.6, -57.6) -27.3 (-75.0, 23.5)
Participant with at least one newly emergent abnormal finding
0 0 1 (33.3%) 1 (20.0%) 1 (33.3%) 3 (20.0%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Urine creatinine
Post-dose value
N 2 2 5 1 10
Mean (SD) 89.7 (56.5) 128.1 (64.8) 78.5 (48.6) 83.5 91.1 (47.6)
Median (Min, Max) 89.7 (49.7, 129.6) 128.1 (82.3, 173.9) 73.5 (8.3, 128.1) 83.5 (83.5, 83.5) 82.9 (8.3, 173.9)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Microalbuminuria
Post-dose value
N 2 2 5 1 10
Mean (SD) 66.9 (54.0) 129.8 (179.0) 118.6 (219.2) 5.0 99.1 (163.9)
Median (Min, Max) 66.9 (28.7, 105.0) 129.8 (3.2, 256.3) 13.5 (7.2, 509.4) 5.0 (5.0, 5.0) 21.1 (3.2, 509.4)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Protein
Pre-dose value
N 0 1 2 0 3
Mean (SD) 100.0 10.0 (0.0) 40.0 (52.0)
Median (Min, Max) 100.0 (100.0, 100.0) 10.0 (10.0, 10.0) 10.0 (10.0, 100.0)
Post-dose value
N 2 2 5 1 10
Mean (SD) 20.0 (0.2) 52.3 (42.0) 30.5 (41.6) 13.2 31.0 (33.6)
Median (Min, Max) 20.0 (19.8, 20.1) 52.3 (22.6, 82.0) 10.0 (6.2, 104.1) 13.2 (13.2, 13.2) 20.0 (6.2, 104.1)
Change from Baseline
N 0 1 2 0 3
Mean (SD) -18.0 6.0 (8.9) -2.0 (15.2)
Median (Min, Max) -18.0 (-18.0, -18.0) 6.0 (-0.3, 12.3) -0.3 (-18.0, 12.3)
95% CI for Median 1 (-18.0, 12.3)
Percentage Change
N 0 1 2 0 3
Mean (SD) -18.0 60.0 (89.1) 34.0 (77.4)
Median (Min, Max) -18.0 (-18.0, -18.0) 60.0 (-3.0, 123.0) -3.0 (-18.0, 123.0)
Participant with at least one newly emergent abnormal finding
0 1 (50.0%) 0 0 1 (9.1%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Albumin/creatinine ratio
Post-dose value
N 2 2 5 1 10
Mean (SD) 116.5 (133.6) 75.5 (101.1) 116.8 (160.5) 6.0 97.4 (126.1)
Median (Min, Max) 116.5 (22.0, 211.0) 75.5 (4.0, 147.0) 69.0 (11.0, 398.0) 6.0 (6.0, 6.0) 45.5 (4.0, 398.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.4.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Urine Results
Safety Population - IC2
Note:1 95% Non-parametric Confidence Interval for median
Baseline measurement defined as closest measurement before first dose administration. Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise).
5
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Protein/creatinine ratio
Pre-dose value
N 0 0 1 0 1
Mean (SD) 0.2 0.2
Median (Min, Max) 0.2 (0.2, 0.2) 0.2 (0.2, 0.2)
Post-dose value
N 2 2 5 1 10
Mean (SD) 0.3 (0.2) 0.4 (0.1) 0.4 (0.3) 0.2 0.4 (0.3)
Median (Min, Max) 0.3 (0.2, 0.4) 0.4 (0.3, 0.5) 0.3 (0.1, 0.8) 0.2 (0.2, 0.2) 0.3 (0.1, 0.8)
Change from Baseline
N 0 0 1 0 1
Mean (SD) 0.1 0.1
Median (Min, Max) 0.1 (0.1, 0.1) 0.1 (0.1, 0.1)
95% CI for Median 1 (., .)
Percentage Change
N 0 0 1 0 1
Mean (SD) 50.0 50.0
Median (Min, Max) 50.0 (50.0, 50.0) 50.0 (50.0, 50.0)
Participant with at least one newly emergent abnormal finding
0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.5.1 Summary of Clinical Laboratory Measurements by Enrollment Group: Iohexol GFR
Safety Population - IC1
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Iohexol Glomerular Filtration
Post-dose value
N 2 1 3 4 2 12
Mean (SD) 37.3 (5.6) 89.7 91.7 (6.4) 91.8 (21.9) 117.4 (37.2) 86.8 (30.0)
Median (Min, Max) 37.3 (33.3, 41.3) 89.7 (89.7, 89.7) 93.0 (84.8, 97.4) 85.5 (73.1, 123.0) 117.4 (91.0, 143.7) 89.6 (33.3, 143.7)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.5.2 Summary of Clinical Laboratory Measurements by Enrollment Group: Iohexol GFR
Safety Population - IC2
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Iohexol Glomerular Filtration
Post-dose value
N 2 1 5 1 9
Mean (SD) 45.79 (3.49) 72.87 98.16 (10.35) 75.62 81.21 (23.68)
Median (Min, Max) 45.79 (43.32, 48.25) 72.87 (72.87, 72.87) 97.12 (86.47, 110.30) 75.62 (75.62, 75.62) 86.47 (43.32, 110.30)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.6 Summary of Clinical Laboratory Measurements by Enrollment Group using Valid Pre-Lisinopril Records
Safety Population - IC2 with Valid Pre-Lisinopril Records
Note:1 95% Non-parametric Confidence Interval for median
Pre-lisinopril values are the average of the chart review records collected <=6 weeks prior to first lisinopril dose recorded on prior and concomitant medications form. Post-dose value calculated as last value while the participant was on drug.
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Creatinine (mg/dL)
Pre-Lisinopril value
N 1 2 2 0 5
Mean (SD) 1.8 1.3 (0.6) 0.7 (0.1) 1.2 (0.5)
Median (Min, Max) 1.8 (1.8, 1.8) 1.3 (0.9, 1.7) 0.7 (0.6, 0.8) 0.9 (0.6, 1.8)
Post-dose value
N 1 2 2 0 5
Mean (SD) 1.9 1.5 (0.9) 0.9 (0.1) 1.3 (0.6)
Median (Min, Max) 1.9 (1.9, 1.9) 1.5 (0.8, 2.1) 0.9 (0.8, 1.0) 1.0 (0.8, 2.1)
Change from Baseline
N 1 2 2 0 5
Mean (SD) 0.2 0.2 (0.4) 0.2 (0.0) 0.2 (0.2)
Median (Min, Max) 0.2 (0.2, 0.2) 0.2 (-0.1, 0.4) 0.2 (0.2, 0.2) 0.2 (-0.1, 0.4)
95% CI for Median 1 (-0.1, 0.4)
Percentage Change
N 1 2 2 0 5
Mean (SD) 9.7 7.7 (25.1) 25.4 (4.1) 15.2 (15.8)
Median (Min, Max) 9.7 (9.7, 9.7) 7.7 (-10.0, 25.4) 25.4 (22.5, 28.3) 22.5 (-10.0, 28.3)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.6 Summary of Clinical Laboratory Measurements by Enrollment Group using Valid Pre-Lisinopril Records
Safety Population - IC2 with Valid Pre-Lisinopril Records
Note:1 95% Non-parametric Confidence Interval for median
Pre-lisinopril values are the average of the chart review records collected <=6 weeks prior to first lisinopril dose recorded on prior and concomitant medications form. Post-dose value calculated as last value while the participant was on drug.
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Potassium (mEq/L)
Pre-Lisinopril value
N 2 2 2 0 6
Mean (SD) 4.7 (0.4) 4.7 (0.2) 3.9 (0.1) 4.4 (0.5)
Median (Min, Max) 4.7 (4.4, 5.0) 4.7 (4.5, 4.8) 3.9 (3.8, 3.9) 4.5 (3.8, 5.0)
Post-dose value
N 2 2 2 0 6
Mean (SD) 4.4 (0.4) 5.0 (0.4) 3.9 (0.8) 4.4 (0.7)
Median (Min, Max) 4.4 (4.1, 4.7) 5.0 (4.7, 5.2) 3.9 (3.3, 4.4) 4.6 (3.3, 5.2)
Change from Baseline
N 2 2 2 0 6
Mean (SD) -0.3 (0.0) 0.3 (0.1) -0.0 (0.7) 0.0 (0.4)
Median (Min, Max) -0.3 (-0.3, -0.3) 0.3 (0.2, 0.4) -0.0 (-0.5, 0.5) -0.0 (-0.5, 0.5)
95% CI for Median 1 (-0.5, 0.5)
Percentage Change
N 2 2 2 0 6
Mean (SD) -5.9 (1.2) 6.4 (2.7) -0.7 (17.7) -0.1 (9.7)
Median (Min, Max) -5.9 (-6.8, -5.1) 6.4 (4.4, 8.3) -0.7 (-13.2, 11.9) -0.3 (-13.2, 11.9)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.2.6 Summary of Clinical Laboratory Measurements by Enrollment Group using Valid Pre-Lisinopril Records
Safety Population - IC2 with Valid Pre-Lisinopril Records
Note:1 95% Non-parametric Confidence Interval for median
Pre-lisinopril values are the average of the chart review records collected <=6 weeks prior to first lisinopril dose recorded on prior and concomitant medications form. Post-dose value calculated as last value while the participant was on drug.
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Calculated eGFR (mL/min per 1.73m²)
Pre-Lisinopril value
N 1 2 2 0 5
Mean (SD) 40.3 41.3 (4.6) 89.7 (9.1) 60.4 (27.2)
Median (Min, Max) 40.3 (40.3, 40.3) 41.3 (38.0, 44.5) 89.7 (83.2, 96.1) 44.5 (38.0, 96.1)
Post-dose value
N 1 2 2 0 5
Mean (SD) 36.7 39.9 (13.5) 71.4 (4.9) 51.9 (19.3)
Median (Min, Max) 36.7 (36.7, 36.7) 39.9 (30.3, 49.5) 71.4 (67.9, 74.9) 49.5 (30.3, 74.9)
Change from Baseline
N 1 2 2 0 5
Mean (SD) -3.6 -1.4 (9.0) -18.3 (4.2) -8.6 (10.2)
Median (Min, Max) -3.6 (-3.6, -3.6) -1.4 (-7.7, 4.9) -18.3 (-21.2, -15.3) -7.7 (-21.2, 4.9)
95% CI for Median 1 (-21.2, 4.9)
Percentage Change
N 1 2 2 0 5
Mean (SD) -8.9 -4.6 (22.2) -20.2 (2.6) -11.7 (13.7)
Median (Min, Max) -8.9 (-8.9, -8.9) -4.6 (-20.3, 11.1) -20.2 (-22.1, -18.4) -18.4 (-22.1, 11.1)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.1 Summary of Vital Signs by Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Weight (kg)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 58.0 (5.4) 110.8 46.2 (5.7) 52.4 (10.7) 26.3 (6.2) 51.0 (21.2)
Median (Min, Max) 57.2 (53.0, 63.7) 110.8 (110.8, 110.8) 44.4 (41.7, 52.6) 55.1 (34.0, 60.9) 25.1 (20.8, 33.0) 53.0 (20.8, 110.8)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 57.5 (4.7) 110.3 47.2 (5.0) 51.4 (11.2) 26.4 (6.0) 50.7 (21.0)
Median (Min, Max) 55.9 (53.8, 62.7) 110.3 (110.3, 110.3) 45.4 (43.3, 52.8) 54.4 (32.6, 61.9) 25.2 (21.0, 32.9) 52.8 (21.0, 110.3)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) -0.5 (1.1) -0.5 0.9 (0.7) -1.0 (1.2) 0.1 (0.2) -0.3 (1.1)
Median (Min, Max) -1.0 (-1.3, 0.8) -0.5 (-0.5, -0.5) 1.0 (0.2, 1.6) -1.4 (-2.0, 1.0) 0.1 (-0.1, 0.2) -0.1 (-2.0, 1.6)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) -0.8 (2.0) -0.5 2.2 (1.7) -2.1 (2.4) 0.4 (0.6) -0.4 (2.3)
Median (Min, Max) -1.6 (-2.3, 1.5) -0.5 (-0.5, -0.5) 2.3 (0.4, 3.8) -3.4 (-4.1, 1.6) 0.4 (-0.3, 1.0) -0.3 (-4.1, 3.8)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.1 Summary of Vital Signs by Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Height (cm)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 148.2 (14.9) 165.5 147.0 (17.7) 149.4 (17.4) 126.7 (15.2) 145.2 (17.5)
Median (Min, Max) 151.0 (132.1, 161.5) 165.5 (165.5, 165.5) 145.0 (130.4, 165.7) 157.1 (122.0, 164.7) 125.6 (112.1, 142.4) 145.0 (112.1, 165.7)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.1 Summary of Vital Signs by Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Temperature (0c)
Pre-dose value
N 3 1 3 4 3 14
Mean (SD) 37.0 (0.5) 37.3 36.6 (0.4) 36.5 (0.5) 37.0 (0.4) 36.8 (0.5)
Median (Min, Max) 36.9 (36.6, 37.5) 37.3 (37.3, 37.3) 36.8 (36.1, 36.8) 36.3 (36.1, 37.2) 37.0 (36.7, 37.4) 36.8 (36.1, 37.5)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 37.1 (0.1) 36.6 36.7 (0.2) 36.4 (0.4) 36.6 (0.1) 36.7 (0.4)
Median (Min, Max) 37.2 (37.0, 37.2) 36.6 (36.6, 36.6) 36.8 (36.5, 36.9) 36.6 (35.7, 36.7) 36.6 (36.5, 36.7) 36.7 (35.7, 37.2)
Change from Baseline
N 3 1 3 4 3 14
Mean (SD) 0.1 (0.6) -0.7 0.2 (0.2) 0.1 (0.6) -0.4 (0.5) -0.1 (0.5)
Median (Min, Max) 0.3 (-0.5, 0.6) -0.7 (-0.7, -0.7) 0.1 (0.0, 0.4) 0.1 (-0.5, 0.6) -0.4 (-0.9, 0.0) 0.0 (-0.9, 0.6)
Percentage Change
N 3 1 3 4 3 14
Mean (SD) 0.4 (1.5) -1.9 0.5 (0.6) 0.2 (1.5) -1.2 (1.2) -0.1 (1.4)
Median (Min, Max) 0.8 (-1.3, 1.6) -1.9 (-1.9, -1.9) 0.3 (0.0, 1.1) 0.3 (-1.3, 1.7) -1.1 (-2.4, 0.0) 0.0 (-2.4, 1.7)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.1 Summary of Vital Signs by Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Systolic Blood Pressure (mm Hg)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 119.7 (5.5) 133.0 122.7 (0.6) 125.8 (9.2) 127.0 (7.8) 124.7 (7.1)
Median (Min, Max) 117.0 (116.0, 126.0) 133.0 (133.0, 133.0) 123.0 (122.0, 123.0) 126.0 (114.0, 137.0) 131.0 (118.0, 132.0) 123.0 (114.0, 137.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 114.7 (11.1) 127.0 116.0 (4.6) 117.0 (5.5) 115.7 (5.9) 116.7 (6.6)
Median (Min, Max) 116.0 (103.0, 125.0) 127.0 (127.0, 127.0) 117.0 (111.0, 120.0) 119.0 (110.0, 124.0) 118.0 (109.0, 120.0) 118.0 (103.0, 127.0)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) -5.0 (11.4) -6.0 -6.7 (4.0) -8.8 (11.7) -11.3 (2.1) -7.9 (8.1)
Median (Min, Max) -10.0 (-13.0, 8.0) -6.0 (-6.0, -6.0) -6.0 (-11.0, -3.0) -10.0 (-19.0, 10.0) -12.0 (-13.0, -9.0) -10.0 (-19.0, 10.0)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) -4.1 (9.6) -4.5 -5.4 (3.3) -6.5 (9.3) -8.9 (1.2) -6.2 (6.5)
Median (Min, Max) -7.9 (-11.2, 6.8) -4.5 (-4.5, -4.5) -4.9 (-9.0, -2.4) -8.3 (-14.4, 8.8) -9.1 (-9.9, -7.6) -7.9 (-14.4, 8.8)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.1 Summary of Vital Signs by Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
5
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Diastolic Blood Pressure (mm Hg)
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 76.0 (18.7) 73.0 75.3 (7.8) 75.4 (8.1) 78.3 (11.9) 75.9 (10.0)
Median (Min, Max) 82.0 (55.0, 91.0) 73.0 (73.0, 73.0) 73.0 (69.0, 84.0) 78.0 (63.0, 83.0) 82.0 (65.0, 88.0) 78.0 (55.0, 91.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 72.0 (3.5) 80.0 66.3 (8.6) 69.4 (13.5) 74.3 (13.4) 71.0 (10.2)
Median (Min, Max) 74.0 (68.0, 74.0) 80.0 (80.0, 80.0) 68.0 (57.0, 74.0) 69.0 (50.0, 86.0) 80.0 (59.0, 84.0) 74.0 (50.0, 86.0)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) -4.0 (20.0) 7.0 -9.0 (7.5) -6.0 (6.7) -4.0 (5.3) -4.9 (9.8)
Median (Min, Max) -14.0 (-17.0, 19.0) 7.0 (7.0, 7.0) -10.0 (-16.0, -1.0) -7.0 (-13.0, 5.0) -6.0 (-8.0, 2.0) -7.0 (-17.0, 19.0)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) -0.4 (30.3) 9.6 -11.8 (10.2) -8.6 (9.7) -5.3 (6.7) -5.7 (14.6)
Median (Min, Max) -17.1 (-18.7, 34.5) 9.6 (9.6, 9.6) -11.9 (-21.9, -1.4) -9.7 (-20.6, 6.2) -9.1 (-9.2, 2.4) -9.2 (-21.9, 34.5)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.1 Summary of Vital Signs by Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
6
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Pulse
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 87.3 (16.2) 102.0 81.7 (8.0) 88.2 (8.2) 96.7 (4.7) 89.3 (10.3)
Median (Min, Max) 90.0 (70.0, 102.0) 102.0 (102.0, 102.0) 81.0 (74.0, 90.0) 86.0 (79.0, 99.0) 95.0 (93.0, 102.0) 90.0 (70.0, 102.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 91.0 (6.6) 104.0 71.7 (11.9) 89.0 (9.0) 89.7 (7.5) 87.1 (11.6)
Median (Min, Max) 92.0 (84.0, 97.0) 104.0 (104.0, 104.0) 77.0 (58.0, 80.0) 92.0 (78.0, 98.0) 90.0 (82.0, 97.0) 90.0 (58.0, 104.0)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) 3.7 (9.6) 2.0 -10.0 (6.0) 0.8 (5.7) -7.0 (7.8) -2.3 (8.1)
Median (Min, Max) 2.0 (-5.0, 14.0) 2.0 (2.0, 2.0) -10.0 (-16.0, -4.0) -1.0 (-5.0, 10.0) -11.0 (-12.0, 2.0) -2.0 (-16.0, 14.0)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) 5.8 (12.8) 2.0 -12.6 (8.4) 1.0 (6.7) -7.2 (8.0) -2.3 (10.1)
Median (Min, Max) 2.2 (-4.9, 20.0) 2.0 (2.0, 2.0) -11.1 (-21.6, -4.9) -1.0 (-6.0, 11.6) -11.8 (-11.8, 2.1) -2.1 (-21.6, 20.0)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.1 Summary of Vital Signs by Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
7
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
Respiration
Pre-dose value
N 3 1 3 5 3 15
Mean (SD) 17.3 (2.3) 14.0 14.7 (1.2) 17.2 (4.1) 22.0 (2.0) 17.5 (3.7)
Median (Min, Max) 16.0 (16.0, 20.0) 14.0 (14.0, 14.0) 14.0 (14.0, 16.0) 18.0 (12.0, 22.0) 22.0 (20.0, 24.0) 16.0 (12.0, 24.0)
Post-dose value
N 3 1 3 5 3 15
Mean (SD) 19.3 (4.2) 18.0 20.7 (4.2) 17.2 (1.8) 20.0 (2.0) 18.9 (2.9)
Median (Min, Max) 18.0 (16.0, 24.0) 18.0 (18.0, 18.0) 22.0 (16.0, 24.0) 16.0 (16.0, 20.0) 20.0 (18.0, 22.0) 18.0 (16.0, 24.0)
Change from Baseline
N 3 1 3 5 3 15
Mean (SD) 2.0 (2.0) 4.0 6.0 (5.3) 0.0 (4.9) -2.0 (2.0) 1.5 (4.5)
Median (Min, Max) 2.0 (0.0, 4.0) 4.0 (4.0, 4.0) 8.0 (0.0, 10.0) 2.0 (-6.0, 6.0) -2.0 (-4.0, 0.0) 2.0 (-6.0, 10.0)
Percentage Change
N 3 1 3 5 3 15
Mean (SD) 10.8 (10.1) 28.6 42.9 (37.8) 5.6 (30.9) -8.9 (8.4) 12.7 (28.9)
Median (Min, Max) 12.5 (0.0, 20.0) 28.6 (28.6, 28.6) 57.1 (0.0, 71.4) 11.1 (-27.3, 50.0) -10.0 (-16.7, 0.0) 11.1 (-27.3, 71.4)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.2 Summary of Vital Signs by Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
1
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Weight (kg)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 77.4 (29.0) 31.2 (22.6) 53.7 (21.9) 45.7 (23.1) 52.5 (24.6)
Median (Min, Max) 77.4 (56.9, 97.9) 31.2 (15.2, 47.2) 54.0 (19.7, 75.7) 45.7 (29.4, 62.0) 54.0 (15.2, 97.9)
Post-dose value
N 2 2 5 1 10
Mean (SD) 77.1 (30.1) 30.8 (22.8) 53.4 (22.4) 29.5 51.2 (26.0)
Median (Min, Max) 77.1 (55.8, 98.3) 30.8 (14.6, 46.9) 53.3 (19.1, 76.5) 29.5 (29.5, 29.5) 50.8 (14.6, 98.3)
Change from Baseline
N 2 2 5 1 10
Mean (SD) -0.4 (1.1) -0.5 (0.2) -0.2 (0.7) 0.1 -0.3 (0.6)
Median (Min, Max) -0.4 (-1.1, 0.4) -0.5 (-0.6, -0.3) -0.6 (-0.9, 0.8) 0.1 (0.1, 0.1) -0.5 (-1.1, 0.8)
Percentage Change
N 2 2 5 1 10
Mean (SD) -0.8 (1.7) -2.3 (2.3) -0.9 (1.7) 0.3 -1.1 (1.7)
Median (Min, Max) -0.8 (-1.9, 0.4) -2.3 (-3.9, -0.6) -1.3 (-3.0, 1.1) 0.3 (0.3, 0.3) -1.0 (-3.9, 1.1)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.2 Summary of Vital Signs by Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
2
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Height (cm)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 156.0 (21.0) 126.3 (41.4) 148.2 (27.4) 143.6 (24.9) 144.8 (26.0)
Median (Min, Max) 156.0 (141.1, 170.8) 126.3 (97.0, 155.6) 151.0 (107.7, 181.5) 143.6 (126.0, 161.2) 151.0 (97.0, 181.5)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.2 Summary of Vital Signs by Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
3
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Temperature (0c)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 36.9 (0.4) 36.9 (0.6) 36.6 (0.3) 36.6 (0.2) 36.7 (0.4)
Median (Min, Max) 36.9 (36.6, 37.2) 36.9 (36.4, 37.3) 36.7 (36.2, 37.0) 36.6 (36.4, 36.7) 36.7 (36.2, 37.3)
Post-dose value
N 2 2 5 1 10
Mean (SD) 36.8 (0.4) 36.6 (0.3) 36.7 (0.2) 36.7 36.7 (0.2)
Median (Min, Max) 36.8 (36.5, 37.1) 36.6 (36.4, 36.8) 36.8 (36.4, 36.9) 36.7 (36.7, 36.7) 36.8 (36.4, 37.1)
Change from Baseline
N 2 2 5 1 10
Mean (SD) -0.1 (0.0) -0.3 (0.9) 0.1 (0.4) 0.3 0.0 (0.5)
Median (Min, Max) -0.1 (-0.1, -0.1) -0.3 (-0.9, 0.4) 0.1 (-0.4, 0.6) 0.3 (0.3, 0.3) 0.0 (-0.9, 0.6)
Percentage Change
N 2 2 5 1 10
Mean (SD) -0.3 (0.0) -0.7 (2.5) 0.4 (1.1) 0.8 0.1 (1.2)
Median (Min, Max) -0.3 (-0.3, -0.3) -0.7 (-2.4, 1.1) 0.3 (-1.1, 1.7) 0.8 (0.8, 0.8) 0.0 (-2.4, 1.7)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.2 Summary of Vital Signs by Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
4
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Systolic Blood Pressure (mm Hg)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 118.0 (12.7) 107.5 (0.7) 118.6 (13.8) 116.0 (4.2) 116.0 (10.6)
Median (Min, Max) 118.0 (109.0, 127.0) 107.5 (107.0, 108.0) 114.0 (106.0, 140.0) 116.0 (113.0, 119.0) 113.0 (106.0, 140.0)
Post-dose value
N 2 2 5 1 10
Mean (SD) 112.0 (29.7) 106.5 (3.5) 125.0 (14.0) 112.0 117.4 (16.0)
Median (Min, Max) 112.0 (91.0, 133.0) 106.5 (104.0, 109.0) 124.0 (112.0, 145.0) 112.0 (112.0, 112.0) 112.0 (91.0, 145.0)
Change from Baseline
N 2 2 5 1 10
Mean (SD) -6.0 (17.0) -1.0 (4.2) 6.4 (6.9) -1.0 1.7 (9.1)
Median (Min, Max) -6.0 (-18.0, 6.0) -1.0 (-4.0, 2.0) 5.0 (0.0, 18.0) -1.0 (-1.0, -1.0) 2.5 (-18.0, 18.0)
Percentage Change
N 2 2 5 1 10
Mean (SD) -5.9 (15.0) -0.9 (3.9) 5.6 (6.1) -0.9 1.3 (8.1)
Median (Min, Max) -5.9 (-16.5, 4.7) -0.9 (-3.7, 1.9) 3.6 (0.0, 15.8) -0.9 (-0.9, -0.9) 2.3 (-16.5, 15.8)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.2 Summary of Vital Signs by Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
5
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Diastolic Blood Pressure (mm Hg)
Pre-dose value
N 2 2 5 2 11
Mean (SD) 71.0 (7.1) 67.5 (2.1) 71.0 (16.0) 63.0 (1.4) 68.9 (10.9)
Median (Min, Max) 71.0 (66.0, 76.0) 67.5 (66.0, 69.0) 64.0 (57.0, 92.0) 63.0 (62.0, 64.0) 66.0 (57.0, 92.0)
Post-dose value
N 2 2 5 1 10
Mean (SD) 65.0 (1.4) 61.0 (11.3) 74.4 (17.9) 61.0 68.5 (14.1)
Median (Min, Max) 65.0 (64.0, 66.0) 61.0 (53.0, 69.0) 73.0 (55.0, 101.0) 61.0 (61.0, 61.0) 65.0 (53.0, 101.0)
Change from Baseline
N 2 2 5 1 10
Mean (SD) -6.0 (5.7) -6.5 (9.2) 3.4 (14.0) -3.0 -1.1 (11.1)
Median (Min, Max) -6.0 (-10.0, -2.0) -6.5 (-13.0, 0.0) 5.0 (-11.0, 23.0) -3.0 (-3.0, -3.0) -2.5 (-13.0, 23.0)
Percentage Change
N 2 2 5 1 10
Mean (SD) -8.1 (7.2) -9.9 (13.9) 6.2 (21.9) -4.7 -1.0 (17.3)
Median (Min, Max) -8.1 (-13.2, -3.0) -9.9 (-19.7, 0.0) 8.8 (-14.1, 39.7) -4.7 (-4.7, -4.7) -3.9 (-19.7, 39.7)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.2 Summary of Vital Signs by Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
6
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Pulse
Pre-dose value
N 2 2 5 2 11
Mean (SD) 85.0 (24.0) 92.5 (10.6) 88.6 (11.9) 81.5 (3.5) 87.4 (11.9)
Median (Min, Max) 85.0 (68.0, 102.0) 92.5 (85.0, 100.0) 81.0 (79.0, 104.0) 81.5 (79.0, 84.0) 84.0 (68.0, 104.0)
Post-dose value
N 2 2 5 1 10
Mean (SD) 82.5 (9.2) 93.0 (2.8) 76.4 (6.1) 72.0 80.5 (8.9)
Median (Min, Max) 82.5 (76.0, 89.0) 93.0 (91.0, 95.0) 74.0 (70.0, 86.0) 72.0 (72.0, 72.0) 77.0 (70.0, 95.0)
Change from Baseline
N 2 2 5 1 10
Mean (SD) -2.5 (14.8) 0.5 (13.4) -12.2 (14.1) -12.0 -7.7 (12.9)
Median (Min, Max) -2.5 (-13.0, 8.0) 0.5 (-9.0, 10.0) -10.0 (-30.0, 7.0) -12.0 (-12.0, -12.0) -9.5 (-30.0, 10.0)
Percentage Change
N 2 2 5 1 10
Mean (SD) -0.5 (17.3) 1.4 (14.7) -12.5 (14.3) -14.3 -7.5 (14.0)
Median (Min, Max) -0.5 (-12.7, 11.8) 1.4 (-9.0, 11.8) -12.5 (-28.8, 8.9) -14.3 (-14.3, -14.3) -10.8 (-28.8, 11.8)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.3.2 Summary of Vital Signs by Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). Trough PK visit blood pressure evaluation before the PK visit dose is used as post-dose value.
7
30 – 59 ml/min per 1.73m² >60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
Respiration
Pre-dose value
N 0 2 4 1 7
Mean (SD) 22.0 (0.0) 19.0 (4.8) 18.0 19.7 (3.7)
Median (Min, Max) 22.0 (22.0, 22.0) 21.0 (12.0, 22.0) 18.0 (18.0, 18.0) 22.0 (12.0, 22.0)
Post-dose value
N 2 2 5 1 10
Mean (SD) 18.0 (0.0) 21.0 (1.4) 18.0 (2.0) 22.0 19.0 (2.2)
Median (Min, Max) 18.0 (18.0, 18.0) 21.0 (20.0, 22.0) 18.0 (16.0, 20.0) 22.0 (22.0, 22.0) 19.0 (16.0, 22.0)
Change from Baseline
N 0 2 4 1 7
Mean (SD) -1.0 (1.4) -0.5 (5.0) 4.0 0.0 (4.0)
Median (Min, Max) -1.0 (-2.0, 0.0) -1.0 (-6.0, 6.0) 4.0 (4.0, 4.0) 0.0 (-6.0, 6.0)
Percentage Change
N 0 2 4 1 7
Mean (SD) -4.6 (6.4) 3.4 (33.1) 22.2 3.8 (25.2)
Median (Min, Max) -4.6 (-9.1, 0.0) -4.6 (-27.3, 50.0) 22.2 (22.2, 22.2) 0.0 (-27.3, 50.0)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.4.1 Summary of Concomitant Medications by Drug Classification, Drug Name and Enrollment Group
Safety Population - IC1
Note: The percentages are based on the total number of enrolled participants in each treatment group or total.
Participants are counted once for each medication after the start of study dose.
1
30 – 59 ml/min per 1.73m² > 60 ml/min per 1.73m²
0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=1) 0.1 mg/kg/day
(N=3) 0.2 mg/kg/day
(N=5) 0.4 mg/kg/day
(N=3) Total
(N=15)
WHO Class Medication Name
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
ALIMENTARY TRACT AND METABOLISM 0 0 0 0 0 0 1 (20%) 1 1 (33.3%) 1 2 (13.3%) 2
ONDANSETRON 0 0 0 0 0 0 1 (20%) 1 0 0 1 (6.7%) 1
VITAMIN D NOS 0 0 0 0 0 0 0 0 1 (33.3%) 1 1 (6.7%) 1
CARDIOVASCULAR SYSTEM
2 (66.7%)
2
1 (100%)
1
1 (33.3%)
1
3 (60%)
3
2 (66.7%)
2
9 (60%)
9
LISINOPRIL 2 (66.7%) 2 1 (100%) 1 1 (33.3%) 1 3 (60%) 3 2 (66.7%) 2 9 (60%) 9
DERMATOLOGICALS
1 (33.3%)
1
0
0
0
0
0
0
0
0
1 (6.7%)
1
BENZOYL PEROXIDE 1 (33.3%) 1 0 0 0 0 0 0 0 0 1 (6.7%) 1
SENSORY ORGANS
0
0
0
0
0
0
1 (20%)
1
0
0
1 (6.7%)
1
CIPRO HC 0 0 0 0 0 0 1 (20%) 1 0 0 1 (6.7%) 1
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.4.2 Summary of Concomitant Medications by Drug Classification, Drug Name and Enrollment Group
Safety Population - IC2
Note: The percentages are based on the total number of enrolled participants in each treatment group or total.
Participants are counted once for each medication after the start of study dose.
1
30 – 59 ml/min per 1.73m² > 60 ml/min per 1.73m²
0.1 mg/kg/day
(N=2) 0.2 mg/kg/day
(N=2) 0.1 mg/kg/day
(N=5) 0.2 mg/kg/day
(N=2) Total
(N=11)
WHO Class Medication Name
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
Pts With Medn N (%)
Total Medns
N
ALIMENTARY TRACT AND METABOLISM 0 0 1 (50%) 1 0 0 0 0 1 (9.1%) 1
ESOMEPRAZOLE 0 0 1 (50%) 1 0 0 0 0 1 (9.1%) 1
ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
1 (50%)
1
0
0
0
0
0
0
1 (9.1%)
1
MYCOPHENOLATE MOFETIL 1 (50%) 1 0 0 0 0 0 0 1 (9.1%) 1
RESPIRATORY SYSTEM
0
0
1 (50%)
1
0
0
0
0
1 (9.1%)
1
MONTELUKAST SODIUM 0 0 1 (50%) 1 0 0 0 0 1 (9.1%) 1
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.5.1 Summary of Physical Examination Abnormal Findings by Body System and Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). 1
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
Timepoint
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Abnormal Findings at Baseline
Participant with at least one abnormal finding at baseline
2 (66.7%) 1 (100.0%) 0 2 (40.0%) 1 (33.3%) 6 (40.0%)
General appearance 0 0 0 0 0 0
General behavior 0 0 0 0 0 0
Skin 1 (33.3%) 1 (100.0%) 0 0 0 2 (13.3%)
Head 0 0 0 0 0 0
Eyes and vision 0 0 0 0 0 0
Ears, nose and throat 1 (33.3%) 0 0 1 (20.0%) 1 (33.3%) 3 (20.0%)
Neck/thyroid 0 0 0 0 0 0
Blood/lymphatic 0 0 0 0 0 0
Cardiovascular 0 0 0 1 (20.0%) 0 1 (6.7%)
Respiratory 0 0 0 0 0 0
Abdomen 0 0 0 1 (20.0%) 1 (33.3%) 2 (13.3%)
Nervous system 0 0 0 0 0 0
Musculoskeletal 1 (33.3%) 0 0 0 0 1 (6.7%)
Extremities 1 (33.3%) 1 (100.0%) 0 0 0 2 (13.3%)
Anorectal/genital 0 0 0 0 0 0
Edema 2 (66.7%) 1 (100.0%) 0 0 0 3 (20.0%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.5.1 Summary of Physical Examination Abnormal Findings by Body System and Enrollment Group
Safety Population - IC1
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). 2
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
Timepoint
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=1)
0.1 mg/kg/day
(N=3)
0.2 mg/kg/day
(N=5)
0.4 mg/kg/day
(N=3) Total
(N=15)
Newly Emergent Abnormal Findings After Study Drug Administration
Participant with at least one newly emergent abnormal finding
1 (33.3%) 1 (100.0%) 0 0 0 2 (13.3%)
General appearance 0 1 (100.0%) 0 0 0 1 (6.7%)
General behavior 0 0 0 0 0 0
Skin 0 0 0 0 0 0
Head 0 0 0 0 0 0
Eyes and vision 0 0 0 0 0 0
Ears, nose and throat 0 0 0 0 0 0
Neck/thyroid 0 0 0 0 0 0
Blood/lymphatic 0 0 0 0 0 0
Cardiovascular 0 0 0 0 0 0
Respiratory 0 0 0 0 0 0
Abdomen 0 0 0 0 0 0
Nervous system 0 0 0 0 0 0
Musculoskeletal 0 0 0 0 0 0
Extremities 0 0 0 0 0 0
Anorectal/genital 0 0 0 0 0 0
Edema 1 (33.3%) 0 0 0 0 1 (6.7%)
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.5.2 Summary of Physical Examination Abnormal Findings by Body System and Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). 1
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
Timepoint
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Abnormal Findings at Baseline
Participant with at least one abnormal finding at baseline
0 2 (100.0%) 2 (40.0%) 1 (50.0%) 5 (45.5%)
General appearance 0 1 (50.0%) 2 (40.0%) 0 3 (27.3%)
General behavior 0 0 1 (20.0%) 0 1 (9.1%)
Skin 0 0 0 0 0
Head 0 0 1 (20.0%) 0 1 (9.1%)
Eyes and vision 0 1 (50.0%) 0 0 1 (9.1%)
Ears, nose and throat 0 0 0 0 0
Neck/thyroid 0 0 0 0 0
Blood/lymphatic 0 0 0 0 0
Cardiovascular 0 0 0 0 0
Respiratory 0 0 0 0 0
Abdomen 0 1 (50.0%) 1 (20.0%) 1 (50.0%) 3 (27.3%)
Nervous system 0 0 0 0 0
Musculoskeletal 0 0 0 0 0
Extremities 0 0 0 0 0
Anorectal/genital 0 0 0 0 0
Edema 0 0 0 0 0
Protocol: NICHD-2011-HTN01 – HTN-Lisinopril PK Data Lock: May 5, 2014 DRAFT (v1.0) CONFIDENTIAL
Table 14.3.5.2 Summary of Physical Examination Abnormal Findings by Body System and Enrollment Group
Safety Population - IC2
Note: Baseline measurement defined as closest measurement before first dose administration.
Post-dose value calculated as last value while the participant was on study drug (PK visit if completed and interim otherwise). 2
30 – 59 ml/min per
1.73m² >60 ml/min per 1.73m²
Timepoint
0.1 mg/kg/day
(N=2)
0.2 mg/kg/day
(N=2)
0.1 mg/kg/day
(N=5)
0.2 mg/kg/day
(N=2) Total
(N=11)
Newly Emergent Abnormal Findings After Study Drug Administration
Participant with at least one newly emergent abnormal finding
2 (100.0%) 1 (50.0%) 0 0 3 (27.3%)
General appearance 1 (50.0%) 0 0 0 1 (9.1%)
General behavior 0 0 0 0 0
Skin 2 (100.0%) 1 (50.0%) 0 0 3 (27.3%)
Head 0 0 0 0 0
Eyes and vision 0 0 0 0 0
Ears, nose and throat 1 (50.0%) 0 0 0 1 (9.1%)
Neck/thyroid 0 0 0 0 0
Blood/lymphatic 0 0 0 0 0
Cardiovascular 0 0 0 0 0
Respiratory 0 0 0 0 0
Abdomen 2 (100.0%) 0 0 0 2 (18.2%)
Nervous system 0 0 0 0 0
Musculoskeletal 0 0 0 0 0
Extremities 0 0 0 0 0
Anorectal/genital 0 0 0 0 0
Edema 0 0 0 0 0