Clinical efficacy and safety of donepezil on cognitive and global functionin patients with Alzheimer's disease - A 24-week, multicenter, double-blind, placebo-controlled study in Japan

This study evaluated efficacy and safety of donepezil hydrochloride (donepe zil) at 5 mg/day in patients with mild to moderately severe Alzheimer's dis ease for 24 weeks in a double-blind, placebo-controlled comparative trial. In this study, 268 patients were enrolled and 39 of these (15%) were withdr awn. In the evaluable population of efficacy, Protocol-Compatible (PC) anal yzed patients (n = 228), better effects than that of placebo were confirmed using two primary efficacy measures: a cognitive performance test, the Jap anese version of the Alzheimer's Disease Assessment Scale - cognitive subsc ale (ADAS-J cog, p = 0.003) and a clinical global assessment, the Japanese version of the Clinical Global Impression of Change (J-CGIC, p = 0.000). Th e superiority of donepezil was also shown by secondary measures: the Sum of the Boxes of the Clinical Dementia Rating (CDR-SB), the Mental Function Im pairment Scale (MENFIS) and the caregiver-rated modified Crichton scale (CM CS). The same results were obtained in the intention-to-treat (ITT) analysi s (n = 263). The incidence of drug-related adverse events was 10% (14/136) in the donepezil and 8% (10/ 131) in the placebo group; no significant diff erence was seen between the two groups. The main adverse events were gastro intestinal symptoms, and these were almost all mild, and they all disappear ed with continued administration or temporary discontinuation of donepezil. These results indicate that the donepezil appears to be effective and well tolerated in patients with mild to moderately severe Alzheimer's disease. Copyright (C) 2000 S. Karger AG, Basel.