A multicentre, randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate Alzheimer's disease: The malt study

Background. Metrifonate is a long-lasting acetylcholinesterase inhibitor be ing developed for the symptomatic treatment of Alzheimer's disease (AD). Objectives. This study compared the efficacy, tolerability and safety of tw o doses of metrifonate in patients with mild-to-moderate AD, over a 26-week treatment period. Methods. Six hundred and five patients were randomized to placebo (n = 208) , a 40/50 mg dose (40 or 50 mg by weight; n = 200) or a 60/80 mg dose (60 o r 80 mg by weight; n = 197) metrifonate. Patients randomized to receive met rifonate were administered a once-daily loading dose of 80 or 120 mg based on weight for 2 weeks, followed by the relevant maintenance dose for 24 wee ks. Four main clinical domains of AD were assessed: cognition (ADAS-cog and MMSE), psychiatric and behavioural symptoms (ADAS-noncog and NPI), instrum ental and basic activities of daily living (DAD) and global functioning (CI BIC-plus, CIBIS-plus and GDS). Results. ADAS-cog performance was significantly improved in the 60/80 mg an d 40/50 mg dose groups, compared with placebo, in the intention-to-treat (I TT) population. In addition, statistically significant treatment difference s were demonstrated between the 60/80 mg dose group and placebo on MMSE, AD AS-noncog, the NPI subitems of hallucinations and apathy, DAD, CIBIC-plus, CIBIS-plus and the GDS, The performance of the 40/50 mg dose group was also significantly superior to placebo on the CIBIS-plus and the NPI subitem ab errant motor behaviour. Conclusions. Metrifonate significantly improved a wide range of symptoms ac ross all four clinical domains of AD in a dose-dependent manner, and was sa fe and well tolerated at both doses studied. Copyright (C) 1999 John Wiley & Sons, Ltd.