Clinical Observation of Montelukast as a Partner Agent for Complementary

Therapy

Study Objectives

• To compare the clinical benefits of adding montelukast to inhaled budesonide with doubling the dose of inhaled budesonide in adult patients who were symptomatic on inhaled budesonide alone

Price DB et al Thorax 2003;58:211-216.

• Patients aged between 15 and 75 years • Diagnosed with asthma for >1 year• Asthma not optimally controlled (as judged

by investigator) • Regular use of inhaled corticosteroids • Baseline FEV1 value 50% predicted• Beta-agonist reversibility in FEV1 12%• Symptoms requiring 1 puff / day of

beta agonist

Inclusion Criteria

Price DB et al Thorax 2003;58:211-216.

Study Design

Montelukast 10 mg once daily +

budesonide 400 µg twice daily

Budesonide 800 µg twice daily +

montelukast placebo

Budesonide 400 µg twice daily

Run-in (4 weeks) Single-blind

Active treatment (12 weeks)Double-blind

0 4 16

Weeks

1

Montelukastplacebo

once daily

(n=889)

(n=448)

(n=441)

Price DB et al Thorax 2003;58:211-216.

Baseline Characteristics

Gender (% female)

Mean age (years)

Mean AM PEF (L/min)

Mean FEV1 (% predicted)

Mean daytime symptom score

Median % nights with awakenings with asthma

Mean daily beta-agonist use (puffs/day)

Mean inhaled corticosteroid dose (g/day)

Montelukast +budesonide 800 g

(n=448)

59

43

385

69.0

2.2

12.3

2.7

730

Budesonide 1600 g(n=441)

61

43

383

68.3

2.2

13.8

2.7

746

Price DB et al Thorax 2003;58:211-216.

Total

(N=889)

60

43

384

68.7

2.2

13.3

2.7

738

AM PEF Continued to Improve from Baseline over the Study in Both Treatment Groups

MeanAM PEF

(L/min)

Days after randomisation-14 -7 0 7 14 21 28 35 42 48 56 63 70 77 84

Montelukast + budesonide 800 µg (n=448)

Budesonide 1600 µg (n=441)

440

390

400

410

420

430

Run-in

Price DB et al Thorax 2003;58:211-216.

Data represent the mean AM PEF measured before administration of study medication. The efficacy analysis considered the last 10 weeks of the 12-week active treatment period.

Montelukast with Budesonide Had a Faster Onset of Action: Evidence from Day 1

MeanAM PEF

(L/min)

Days relative to randomisation

420

Run-in

390

400

410

Montelukast + budesonide 800 µg (n=448)

Budesonide 1600 µg (n=441)

-14 -7 0 14

3

p<0.001between groups

Price DB et al Thorax 2003;58:211-216.

Mean percentage change from baseline in AM PEF

Patients(n)

0

50

100

150

-50 0 50 100 150 -50 0 50 100 150

Distribution of Response in AM PEFMontelukast + budesonide 800 µg (n=448)

Budesonide 1600 µg (n=441)

Price DB et al Thorax 2003;58:211-216.

Montelukast with Budesonide Was More Effective in Patients with Comorbid Allergic Rhinitis

Data on file, MSD.

Montelukast + budesonide 800 g Budesonide 1600 g

Change from

baseline in

AM PEF(L/min)

All asthma patients Asthma patients withconfirmed allergic rhinitis

0

10

20

30

40p=NS

n=433 n=425 n=216 n=184

p=0.028

Results of a post hoc analysis of patients with asthma and allergic rhinitis

53%53% Additionalimprovement

Improvement from Baseline in Quality of Life Scores

Montelukast + budesonide 800 g(n=448)

Budesonide 1600 g(n=441)

Meanchangefrom

baselinein score

*0.5 represents the minimal important difference in Quality of Life Questionnaire score (Juniper EF et al J Clin Epidemiol 1994;47:81-87.)

p=0.091

Overall Symptoms Activities Emotional Environmentalstimuli

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8 0.71

0.59

*

Price DB et al Thorax 2003;58:211-216.

Average Daily Use of Beta Agonist

Meanbeta-agonist

use(puffs/day)

p=0.510

Budesonide 1600 g (n=441)

Montelukast + budesonide 800 g (n=448)3.0

2.8

2.6

2.4

2.2

2.0

Weeks after randomisation0 2 4 6 8 10 12

Price DB et al Thorax 2003;58:211-216.

Meandaytime

symptomscore

Average Daytime Asthma Symptom Score

0 2 4 6 8 10 12

2.3

2.2

2.1

2.0

1.9

1.8

1.7

p=0.908

Weeks after randomisation

Budesonide 1600 g (n=441)

Montelukast + budesonide 800 g (n=448)

Price DB et al Thorax 2003;58:211-216.

Asthma Exacerbations andAsthma-Free Days

• An asthma exacerbation day was defined as a day with any one of the following events– A decrease from baseline in AM PEF of >20%– AM PEF <180 L/min– An increase from baseline in beta-agonist use of >70% (and a minimum increase of 2 puffs)– An increase from baseline in symptom score of 50%– An asthma attack

• An asthma-free day was defined as a day free of:– Oral corticosteroid use– Emergency care– Nocturnal awakenings

with use of 2 puffs of beta agonist

Price DB et al Thorax 2003;58:211-216.

Days with Asthma Exacerbations

Montelukast +budesonide 800 g

(n=448)

Mediandays withasthma

exacerbations(%)

Budesonide 1600 g(n=441)

p=0.781

0

1

2

3

4

5

6

7 6.76.3

Price DB et al Thorax 2003;58:211-216.

Asthma-Free Days during 12 Weeks of Treatment

Medianasthma-free

days(%)

0

20

40

60

80

100

Montelukast +budesonide 800 g

(n=448)

Budesonide 1600 g(n=441)

86.782.2

p=0.371

Price DB et al Thorax 2003;58:211-216.

Nocturnal Awakenings with Asthma at Baseline and during 12 Weeks of Treatment

Mediannights withawakeningswith asthma

(%)

Montelukast +budesonide 800 g

(n=448)

Budesonide 1600 g(n=441)

2.3

13.812.3

3.9

Baseline Treatment Baseline Treatment

81.3%Fewer nightswith awakenings

71.7%Fewer nightswith awakenings

p=0.353

0

2

4

6

8

10

12

14

16

Price DB et al Thorax 2003;58:211-216.

Patients Who Discontinued Study Treatment due to Worsening Asthma

Patients (n)

0

1

2

3

4

5

6

7

8

Montelukast + budesonide 800 g

(n=448)

Budesonide 1600 g(n=441)

2

7

p=0.105

Price DB et al Thorax 2003;58:211-216.

Patients Requiring Oral Steroids or Admission to Hospital

Patients(%)

Montelukast + budesonide 800 g

(n=448)

Budesonide 1600 g(n=441)

1.6

2.3

0

0.5

1

1.5

2

2.5

3 p=0.472

Price DB et al Thorax 2003;58:211-216.

Tolerability Profile

Adverse events

Patients with 1 adverse event

Respiratory system adverse events

Montelukast +budesonide 800 g

(n=448)

37.1%

11.6%

Budesonide 1600 g(n=441)

41.3%

16.6%

p value

ns

<0.05

Price DB et al Thorax 2003;58:211-216.

Summary

• In COMPACT, treatment with montelukast 10 mg with budesonide 800 g

– Was at least as effective as doubling the budesonide dose to 1600 g

– Was more effective than doubling the dose of budesonide in a post hoc substudy of patients with asthma and allergic rhinitis

– Had a faster onset of action than doubling the budesonide dose to 1600 g

• Both treatments were generally well tolerated, with no significant difference in overall incidence of adverse events

• There was a significantly lower incidence of respiratory adverse events with montelukast with budesonide 800 g compared with budesonide 1600 g (p<0.05)

Price DB et al Thorax 2003;58:211-216.

References

See notes page for references

Before prescribing, please consult the manufacturers’ prescribing information.

Merck does not recommend the use of any product in any different manner than as described in the

prescribing information.

Copyright © 2004 Merck & Co., Inc., Whitehouse Station, NJ, USA.

All rights reserved. 3-05 SGA 2002-W-6560-SS Printed in USA

VISIT US ON THE WORLD WIDE WEB AT http://www.merck.com