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Hager K.,Clinic for Medicine of the Elderly | Baseman A.S.,Janssen Research and Development LLC | Nye J.S.,Janssen Research and Development LLC | Brashear H.R.,Janssen Research and Development LLC | And 4 more authors.
Neuropsychiatric Disease and Treatment | Year: 2014

Background: Currently 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. Methods: In 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. Results: In 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. Conclusion: Long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients. Identification: This study is registered at ClinicalTrials.gov (NCT00679627). © 2014 Hager et al.


PubMed | Clinic for Medicine of the Elderly, The Mount Sinai Medical Center, Synaptec Inc. and Janssen Research and Development LLC
Type: | Journal: Neuropsychiatric disease and treatment | Year: 2014

Currently available treatments for Alzheimers 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.In 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.In 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.Long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients.This study is registered at ClinicalTrials.gov (NCT00679627).


PubMed | Clinic for Medicine of the Elderly, The Mount Sinai Medical Center, Janssen Research and Development LLC and Synaptec Inc
Type: Journal Article | Journal: Alzheimer's research & therapy | Year: 2016

A large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimers disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. A post-hoc analysis was conducted to study the effect of (the presence or absence of) concomitant memantine use on treatment outcome.Randomized patients (N=2045) were divided into subgroups based on memantine use. Analyses included demographic and clinical characteristics (age, nursing home placement, Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) scores) and mortality endpoints.Overall, 496 (24.3%) patients were memantine users and were older (mean (SD), 74.0 (8.76) vs 72.8 (8.76), p=0.008), with lower MMSE scores (18.2 (4.16) vs 19.2 (4.02), p<0.0001) and DAD scores (58.0 (23.49) vs 62.5 (20.52), p<0.0001) than nonusers. Mortality rates (per 100 patient-years) in memantine nonusers (n=1549) were lower for galantamine (1.39) vs placebo-treated patients (4.15). In memantine users, mortality rates were similar for placebo-treated (4.49) and galantamine-treated patients (5.57). In memantine nonusers at 24months, the decline in MMSE scores (effect size (95% CI) 0.25 (0.14; 0.36)) and DAD scores (0.17 (0.06; 0.28)) from baseline was lower in galantamine patients vs placebo patients. The absence of these benefits in memantine users could not be explained by baseline age, MMSE, or DAD scores.This post-hoc analysis shows that the beneficial effects of galantamine at 2years post treatment were not observed in patients who had been placed on background memantine. The reasons for memantine treatment and the possibility of interaction between memantine and galantamine merit further investigation.ClinicalTrials.gov NCT00679627 . Registered 15 May 2008.

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