Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease

Abstract

BackgroundCurrently available treatments for Alzheimer’s disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD.MethodsIn this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the ‘last observation carried forward’ approach, in an analysis of covariance model.ResultsIn all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (−2.14 [4.34]) compared with the galantamine group (−1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (−10.81 [18.27]) versus the galantamine group (−8.16 [17.25]) (P=0.002). Incidences of treatment-emergent adverse events were 54.0% for the galantamine and 48.6% for the placebo group.ConclusionLong-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients.IdentificationThis study is registered at ClinicalTrials.gov (NCT00679627).

Long-term effect of galantamine on cognitive function in patients with Alzheimer&rsquo;s disease versus a simulated disease trajectory: an observational study in the clinical setting

“…Similar to the present results, two previous placebo-controlled studies have demonstrated long-term beneficial effects of ChEI therapy 6,19. On the other hand, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Australian Imaging, Biomarkers and Lifestyle study obtained opposing results, with greater cognitive decline amongst AD patients taking ChEIs compared with those not using ChEIs 20.…”

Longitudinal Associations between Survival in Alzheimer's Disease and Cholinesterase Inhibitor Use, Progression, and Community-Based Services

“…However, the American cohort was considerably younger and better educated than the European cohorts. A recent 2-year randomized placebo-controlled trial reported lower mortality in a galantamine-treated group compared with placebo (3.2 vs. 5.5%) [27]. In the SATS, 5.9% of the individuals had died after 2 years, but their mean age at the start of ChEI therapy was 3 years older.…”

Combination Therapy with Cholinesterase Inhibitors and Memantine for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

“…In a recent study, Hager et al (2014) reported that 437 patients taking memantine and 1375 AD patients not taking this drug were randomly assigned to galantamine or placebo and were followed-up for 2 years. In posthoc analysis of this study, among patients not taking memantine, the galantamine group showed a 1.12-point decrease on MMSE and the placebo group showed a 2.15-point decrease.…”