VELNACRINE FOR THE TREATMENT OF ALZHEIMERS-DISEASE - A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

The present study examines the safety and efficacy of the centrally ac ting cholinesterase inhibitor, velnacrine, in treating the cognitive s ymptoms of Alzheimer's disease. Seven hundred thirty-five patients wit h mild-to-severe Alzheimer's disease were treated in a double-blind, p lacebo-controlled study. Following the screen visit, patients were tre ated with velnacrine (10, 25, 50 and 75 mg t.i.d.) or placebo in a dou ble-blind dose-ranging study to identify velnacrine-responsive patient s and their best dose. Following placebo washout velnacrine responsive patients were randomly assigned to their best dose of velnacrine (N = 153) or placebo (N = 156) in a six week double-blind dose-replication study. Primary efficacy measures were the cognitive subscale of the A lzheimer's Disease Assessment Scale (ADAS) and the Physician's Clinica l Global Impression of Change. Statistically significant improvement w as observed in both primary efficacy measures in velnacrine-treated pa tients during the dose-replication study. Velnacrine patients scored b etter on the cognitive subscale of the ADAS than placebo patients (P < 0.001), with patients receiving the highest velnacrine dose averaging a 4.1-point improvement with respect to screen values. Clinical Globa l Impression of Change scores of velnacrine-treated patients were sign ificantly improved at the end of the 6 weeks of treatment when compare d to those of placebo patients (P < 0.05), The most common side effect was asymptomatic elevation in liver transaminase levels, which occurr ed among 29% of patients. These data suggest that velnacrine produces modest clinical improvement in a subset of patients with mild-to-sever e Alzheimer's disease.