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From the Departments of Neurology and Psychiatry & Biobehavioral Sciences, UCLA School of Medicine and the Neuropsychiatry and Neurobehavior Section, Psychiatry Service, West Los Angeles Veterans Affairs Medical Center(Dr. Cummings), Los Angeles, CA; and Bayer Corporation, Pharmaceutical Division (Drs. Cyrus, Bieber, Orazem, Gulanski and J. Mas), West Haven, CT.
Address correspondence and reprint requests to Dr. Jeffrey L. Cummings, Reed Neurological Research Center, UCLA School of Medicine, 710 Westwood Plaza, Los Angeles, CA 90095-1769.
The efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, was evaluated clinically in patients diagnosed with mild to moderate Alzheimer's disease (AD). This was a prospective, 30-week, multicenter, double-blind, randomized, parallel group, dose-finding study, which included a 2-week screening period, a 12-week treatment period, and follow-up visits at 8 and 16 weeks post-treatment. Patients received placebo or metrifonate once daily. Metrifonate-treated patients received a loading dose of 0.5 mg/kg(25 to 45 mg), 0.9 mg/kg (45 to 80 mg), or 2.0 mg/kg (100 to 180 mg) for 2 weeks, followed by a maintenance dose of 0.2 mg/kg (10 to 20 mg), 0.3 mg/kg(15 to 25 mg), or 0.65 mg/kg (30 to 60 mg) for 10 weeks. Four hundred eighty patients were enrolled. Percentages of patients completing double-blind treatment were 96% in the placebo group and 89 to 94% in the metrifonate group. Metrifonate significantly improved cognitive ability, as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and enhanced global function, as assessed the Clinicians's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus). At 3 months, in the intent-to-treat patients, the treatment difference for the change in ADAS-Cog score in favor of metrifonate was 2.94 points (95% CI, 1.61 to 4.27;p = 0.0001). These patients also exhibited a 0.35-point improvement on the CIBIC-Plus relative to the placebo patients (95% CI, 0.15 to 0.54; p = 0.0007). Patients receiving lower drug doses had scores intermediate to those of the placebo and the 0.65 mg/kg metrifonate groups on both performance scales. The drug was well tolerated; side effects were predominantly gastrointestinal in nature, and no hepatic toxicity was observed. Therefore, in this study, metrifonate safely improved the cognitive deficits and benefited the global function of AD patients.
*See the Appendix on page 1220 for a list of members of the Metrifonate Study Group.
Received June 16, 1997. Accepted in final form October 25, 1997.
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 Other articles noted Evid. Based Ment. Health, November 1, 1998; 1(4): 100 - 100. [Full Text]
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