title: Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease.
abstract: 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.
  
  
  CONCLUSIONS
  Long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients.
  
  
  METHODS
  This study is registered at ClinicalTrials.gov (NCT00679627).
authors.affiliation: Clinic for Medicine of the Elderly, Hannover, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hager
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Baseman
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Nye
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ, USA.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Brashear
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ, USA.
authors.forename: John
authors.initials: J
authors.lastname: Han
authors.affiliation: The Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.affiliation: Synaptec Inc., Palm Beach Gardens, FL, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Davis
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ, USA.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Richards
keywords: cholinesterase inhibitors; cognition; long-term treatment; mortality; nicotinic