Extended-release Memantine (28 mg, Once Daily) Improves verbal fluency and behavior in Patients with Moderate to Severe Alzheimer´s Disease: results of a multinational, double-blind, placebo-controlled trial

GEORGE GROSSBERG; FACUNDO MANES; RICARDO ALLEGRI; LUIS MIGUEL GUTIERREZ ROBLEDO; SERGIO GLOGER; LIE XIE; DANIEL JIA; JAMES PERHACH; STEPHEN GRAHAM

Washington

Encuentro; 61st AAN 2009 Annual Meeting; 2009

American Academy of Neurology

OBJECTIVE: Top-line results were reported previously; this analysis focuses on additional outcome measures of verbal fluency and behavior. BACKGROUND: Memantine is indicated for the treatment of moderate to severe Alzheimer's disease (AD). In the US, it is administered in two daily doses of 10 mg each (20 mg/day) as an immediate-release tablet or solution. This multinational study evaluated the safety, tolerability, and efficacy of once-daily extended-release memantine capsules in outpatients with moderate to severe AD who were receiving concurrent, stable, cholinesterase inhibitor (ChEI) treatment. DESIGN/METHODS: All patients first completed a 2-week, single-blind, placebo-only period, followed by a 24-week, double-blind period of treatment with once-daily extended-release memantine (28 mg) or placebo. Primary outcome measures have been reported; additional measures included a Verbal Fluency test and a behavioral assessment tool, the NPI. Total score changes from Baseline to Week 24 were analyzed using ANCOVA. RESULTS: A total of 677 patients (mean MMSE 10.8 [range 3-17]) were randomized to receive extended-release memantine (n=342) or placebo (n=335), of which 273 (79.8%) and 272 (81.2%) completed the trial, respectively. At Week 24, memantine/ChEI-treated patients demonstrated statistically superior (LOCF) performance compared to placebo/ChEI-treated patients on both the Verbal Fluency test (P=0.004), and the NPI (P=0.005), with additional significant improvements observed at Weeks 12 and 18. Other outcome measures demonstrating significance over placebo in the memantine/ChEI group at Week 24 included the SIB (P=0.001) and the CIBIC-Plus (P=0.008). The adverse events (AEs) profile was similar between the two groups; most AEs in both groups were mild or moderate in severity. CONCLUSIONS/RELEVANCE: Extended-release memantine (28 mg), given once daily, is an effective, safe, and well-tolerated therapy for patients with moderate to severe AD. Improvements observed in verbal fluency and behavior further support the view that the benefits of memantine treatment extend over several clinical domains of dementia. Supported by: Forest Labortories, Inc.