wilcock g., möbius h.j. and stöffler a. on behalf of the mmm500 group

A Double-blind, Placebo-controlled Multicentre Study of Memantine in Mild

to Moderate Vascular Dementia (MMM500)

Wilcock G., Möbius H.J. and Stöffler A. on behalf of the MMM500 group

Int Clin Psychopharmacol 2002, 17(6):297–305

No. of patients N = 579

Design Double-blind, randomized, placebo-controlled, multicenter study

Diagnosis Probable VaD (HIS score ≥ 4, DSM-III-R, NINDS-AIREN)

Age ≥ 54 years (mean 77)

Severity MMSE 10 – 22 (mean 17.6)

Dose; duration 20 mg memantine/day; 28 weeks

Primary efficacy Cognition: ADAS-cogparameters Global: CGI-C

Secondary efficacy MMSE, GBS, NOSGER parameters

Study Design

Wilcock et al., Int Clin Psychopharmacol 2002

Disposition of Patients

Wilcock et al., Int Clin Psychopharmacol 2002

Patients screenedN = 840

Patients randomizedN = 579

Screen failuresN = 261 (31%)

CompletedN = 226(80%)

WithdrewN = 58(20%)

PlaceboN = 284 (49%)

MemantineN = 295 (51%)

CompletedN = 238(81%)

WithdrewN = 57(19%)

24

25

26

27

28

290 12 28

Week

Dec

line

ITT, LOCF ADAS-cog total score

Significant Benefit of Memantine on Cognition (ADAS-cog)

Wilcock et al., Int Clin Psychopharmacol 2002

* p < 0.05 versus placebo

*

AD

AS

-cog

tot

al s

core

Memantine (20 mg/day)

Placebo

-2

0

2

40 12 28

Week

ITT, LOCF Mean change from baseline

Wilcock et al., Int Clin Psychopharmacol 2002

* p < 0.05 versus placebo

*

Significant Benefit of Memantine on Cognition (ADAS-cog)

AD

AS

-cog

sco

re d

iffer

ence

Dec

line

Impr

ovem

ent

Memantine (20 mg/day)

Placebo

Good Safety and Tolerability of Memantine

Adverse events in mild to moderate VaD (MMM500)

Wilcock et al., Int Clin Psychopharmacol 2002

Memantine Placebo

No. of patients 295 (100%) 284 (100%)

No. of patients with AEs 226 (77%) 212 (75%)

Dizziness 33 (11%) 23 (8%)

Inflicted injury 17 (6%) 30 (11%)

Confusion 22 (7%) 21 (7%)

Constipation 30 (10%) 12 (4%)

Bronchitis 20 (7%) 20 (7%)

Headache 21 (7%) 19 (7%)

Fall 18 (6%) 21 (7%)

Coughing 20 (7%) 15 (5%)

Agitation 11 (4%) 23 (8%)

Summary

• Significant cognitive benefit for memantine treated patients in mild to moderate vascular dementia

• Good safety and tolerability of memantine

Wilcock et al., Int Clin Psychopharmacol 2002