Objective: Several well-controlled and open-label clinical trials have demonstrated that 6 to 12 months of treatment with galantamine produces consistent positive effects on global ratings, cognitive tests, and assessments of activities of daily living and behavior in patients with mild-to-moderate Alzheimer’s disease (AD). In this study, the sustained cognitive efficacy of galantamine treatment for 36 months in patients with mild-to-moderate AD was evaluated. In addition, the effects of galantamine discontinuation on the overall cognitive efficacy results during the 3-year period were assessed.
Design: Patients were assigned to receive 24 mg/day of galantamine for 24 months in this open-label extension trial. Patients had previously received 6 to 12 months of galantamine therapy from 1 of 2 previous international clinical trials (one a randomized, double-blind, placebo-controlled, 6-month trial followed by a 6-month, open-label extension trial; the other a randomized, double-blind, placebo-controlled, 3-month trial followed by a 9-month, open-label extension).
Materials and methods: The primary efficacy measures were the standard 11-item Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog/11) and Disability Assessment for Dementia (DAD) instruments. Safety evaluations also were performed. ADAS-cog/11 scores of patients in this study were compared with those of untreated patients using 2 methods: 1) change in ADAS-cog/11 scores from the placebo group of a 1-year, double-blind, placebo-controlled clinical trial; and 2) projected change in ADAS-cog/11 score using mean patient demographics and the methodology of Stern and colleagues. Cognitive efficacy values of patients who completed the entire 36-month trial were statistically compared with the last 2 efficacy values for patients who withdrew from the study for any reason.
Results: There was an initial improvement in cognitive function during the first 6 months of treatment with galantamine, followed by a slow worsening (increase) of ADAS-cog/11 scores during the course of the study. At 36 months, ADAS-cog/11 scores increased by a mean (SEM) of 12.4 (0.80) points (p < 0.001) compared with a projected 22.4-point increase if patients were to remain untreated. Patients who completed the study were not statistically different from the overall study population, including those who had discontinued therapy for any reason (p > 0.1). Total DAD scores decreased (deteriorated) significantly at each time point compared with baseline (p < 0.001). The most common treatment-emergent adverse events were agitation (16.1%), insomnia (12.4%), fall (11.2%), and urinary tract infection (10.2%); however, adverse events were mainly mild to moderate, and few were judged to be treatment related.
Conclusions: The cognitive benefits of galantamine are sustained for at least 36 months versus the expected decline in patients with AD. Sustained clinical efficacy was thus not affected by premature discontinuation from the study, regardless of any reason.
Back to PB Tuesday Poster Sessions
Back to The Eleventh International Congress