Objective: To report the long-term safety and effectiveness of galantamine when given continuously for up to 36 months in patients with mild-to-moderate Alzheimer’s disease (AD) and to determine whether the apparent slowing of decline in patients taking galantamine for 36 months is attributable to “nonresponders” being overrepresented among patients who did not complete the study.
Design: This open-label extension trial was conducted with mild-to-moderate AD patients who had previously participated in one of two double-blind, placebo-controlled trials, as well as subsequent open-label extension phases of these double-blind trials. All patients entering the current trial previously had a minimum of 6 months of galantamine treatment. In the current open-label phase, all patients received galantamine 24 mg/day for up to an additional 24 months (total potential galantamine exposure of up to 36 months).
Materials and Methods: Effects of treatment on cognition were analyzed using the change from baseline in scores on the Alzheimer’s Disease Assessment Scale–11-item cognitive subscale (ADAS-cog/11) after galantamine treatment for 36 months. Cognitive decline was compared in subjects treated with galantamine versus a clinically similar “historical control” sample of AD patients who had received placebo for 12 months, and versus “untreated” patients over 36 months as predicted by the methodology of Stern and colleagues. An inverted responder analysis and safety evaluations also were performed. To assess the effect of patient discontinuation over 36 months on the overall cognitive efficacy results, a random coefficient model was used to analyze dropouts. Here, changes in ADAS-cog/11 scores for each patient were calculated and applied to a t-test that compared the slope and intercept of a line depicting the change for the entire group as well as for each patient as a random subject. This analysis was done using the last 2 observed values and all observed values.
Results: Patients treated continuously with galantamine for 36 months had a mean increase of 10.2 ± 0.9 ADAS-cog/11 points, which was substantially less (approximately 50%) than the expected increase for untreated patients. Patients discontinuing galantamine before 36 months declined at a rate similar to that of patients completing 36 months of treatment. The inverted responder analysis indicated that almost 80% of patients who received galantamine continuously for up to 36 months appeared to demonstrate cognitive benefits. Galantamine was safe and well tolerated when administered continuously for up to 36 months. Most adverse events were mild or moderate in severity and consistent with the findings of previous clinical trials.
Conclusion: The cognitive benefits of galantamine are sustained for at least 36 months versus the expected decline in patients with AD. Nonresponders dropping out of the study was not a reason for the clinical benefit demonstrated in the study.
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