Safety and tolerability of extended-release Memantine (Once Daily, 28 mg) in patients with moderate to severe Alzheimer’s Disease: An Open-Label Extension Study

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

Toronto

Encuentro; 62nd AAN 2011 Annual Meeting; 2010

American Academy of Neurology

OBJECTIVE: To evaluate the long-term safety and tolerability of a once-daily extended-release (ER) memantine capsule in outpatients with moderate to severe Alzheimer's disease (AD), who were receiving stable, concurrent cholinesterase inhibitor (ChEI) treatment. BACKGROUND: In the US, memantine is approved for the treatment of moderate to severe AD as an immediate-release formulation (10 mg BID; 20 mg/day). This study was an open-label extension of a previously reported Phase III trial of memantine ER (28 mg). DESIGN/METHODS: A 24-week trial in moderate to severe AD (MEM-MD-50) was followed by this 28-week open-label extension study (MEM-MD-54). Patients treated with placebo (Pbo/MemER group) and memantine (MemER/MemER group) in the lead-in trial were both titrated to 28 mg memantine ER. Tolerability was assessed by monitoring adverse events (AEs); safety was assessed using laboratory tests, physical exams, and electrocardiograms. RESULTS: In groups Pbo/MemER (n=245) and MemER/MemER (n=246), 86.5% and 85.8% patients completed the trial, respectively, with 8.2% and 10.2% patients discontinuing due to AEs. A total of 64.1% and 58.1% patients in each group, respectively, experienced an AE, and 9.4% and 12.2% experienced a serious AE. Overall, the most frequent AEs were urinary tract infection (6.7%), fall (6.5%), dizziness (4.7%), insomnia (4.7%), and agitation (4.5%), with rates similar between the two groups, except for dizziness (Pbo/MemER, 6.1%; MemER/MemER: 3.3%) and agitation (Pbo/MemER; 1.6%; MemER/MemER: 7.3%). Weight increase (19.6%), weight decrease (12.8%), and high blood urea nitrogen (4.8%) were overall the most frequent parameters with potentially clinically significant changes. CONCLUSIONS/RELEVANCE: Extended-release memantine (once daily, 28 mg) is safe and well tolerated in patients with moderate to severe AD. Supported by: Forest Laboratories, Inc.