METRIFONATE TREATMENT OF THE COGNITIVE DEFICITS OF ALZHEIMERS-DISEASE

The efficacy and safety of metrifonate, an acetylcholinesterase inhibi tor, was evaluated clinically in patients diagnosed with mild to moder ate Alzheimer's disease (AD). This was a prospective, 30-week, multice nter, double-blind, randomized, parallel group, dose-finding study, wh ich included a 2-week screening period, a 12-week treatment period, an d follow-up visits at 8 and 16 weeks post-treatment. Patients received placebo or metrifonate once daily. Metrifonate-treated patients recei ved 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/k g (30 to 60 mg) for 10 weeks. Four hundred eighty patients were enroll ed. Percentages of patients completing double-blind treatment were 96% in the placebo group and 89 to 94% in the metrifonate group. Metrifon ate significantly improved cognitive ability, as assessed by the Alzhe imer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and enh anced global function, as assessed the Clinicians's Interview-Based Im pression 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, 1.6 1 to 4.27; p = 0.0001). These patients also exhibited a 0.35-point imp rovement 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 scor es 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 im proved the cognitive deficits and benefited the global function of AD patients.