A 6-month, double-blind, placebo-controlled trial of eptastigmine in Alzheimer's disease

Objectives: To evaluate the efficacy and safety of eptastigmine as a treatm ent for patients with mild-to-moderate Alzheimer's disease (AD), Patients a nd Methods: The study was designed as a randomized, double-blind, placebo-c ontrolled, parallel-group study. It was performed in 26 Italian and America n geriatric and neurological centers. The study group comprised 349 outpati ents with a diagnosis of probable AD according to the criteria of the Natio nal Institute of Neurological and Communicative Disorders and Stroke and th e AD and Related Disorders Association. Patients were assigned to one of th e three study groups: placebo (n = 119), eptastigmine 10 mg t.i.d. (n = 115 ) or eptastigmine 12 mg t.i.d. (n = 115) for 25 weeks, The AD Assessment Co gnitive Subscale (ADAS-Cog) and the Clinical Dementia Rating Scale-Sum of t he Boxes (CDR-SB) were the primary outcome measures for efficacy, Results: The two doses of eptastigmine produced similar results and are presented to gether. Percentages of patients completing double-blind treatment were 82 a nd 87% in the placebo and eptastigmine groups, respectively. At the end of treatment, the intent-to-treat analysis on 342 patients showed a statistica lly significant effect of eptastigmine compared to placebo on both ADAS-Cog (p = 0.047) and CDR-SB (p = 0.010). Patients on eptastigmine performed sig nificantly better than placebo-treated patients also on the Mini-Mental Sta te Examination (p < 0.001). The drug was well tolerated with 5% of patients withdrawing due to adverse events versus 3% on placebo, Adverse events wer e recorded in 46% of the patients on placebo compared to 52% of the patient s taking eptastigmine, Cholinergic side effects (nausea, vomiting, diarrhea and abdominal pain) were reported with similar frequency in the eptastigmi ne and placebo-treated patients. Conclusion: Eptastigmine doses up to 12 mg t.i.d. for 25 weeks are well tolerated. The drug positively affects cognit ive performance and global function of patients with mild-to-moderate AD. C opyright (C) 2000 S.Karger AG, Basel.