A multinational, randomized, double-blind, placebo-controlled, parallel-group trial of memantine extended-release capsule (28 mg, once daily) in patients with moderate to severe Alzheimer¡¯s disease

GEORGE T. GROSSBERG, FACUNDO MANES, RICARDO ALLEGRI, LUIS MIGUEL GUTIERREZ ROBLEDO, SERGIO GLOGER, LEI XIE, XINWEI DANIEL JIA, JAMES L. PERHACH, AND STEPHEN M. GRAHAM.

NEW ENGLAND JOURNAL OF MEDICINE

MASSACHUSETTS MEDICAL SOC

Lugar: Massachusetts; Año: 2012

0028-4793

Objective: Memantine, approved for moderate to severe Alzheimer¡¯s disease (AD), is administered in the US as a twice-daily, immediate-release formulation (20 mg/day). A once-daily formulation would likely increase compliance and facilitate care-giving. This study evaluated the efficacy, safety, and tolerability of once-daily extended-release (ER) memantine in outpatients with AD on a stable cholinesterase inhibitor (ChEI) therapy. Methods: In this multinational study, all patients (MMSE range: 3-14) first completed a 2-week, single-blind, placebo-only period, followed by a 24-week, double-blind period of treatment with memantine ER (28 mg, QD) or placebo. Primary efficacy parameters were baseline-to-endpoint change on the SIB and endpoint CIBIC-Plus score; additional measures included baseline-to-endpoint changes on the ADCS-ADL19, NPI, and a verbal fluency (VF) test. SIB, ADCS-ADL19, NPI, and VF, were analyzed using a two-way ANCOVA model; CIBIC-Plus data were analyzed using a Cochran-Mantel-Haenszel test. Safety and tolerability were assessed in physical and laboratory examinations, and by recording adverse events (AEs). Results: Completion rates were 79.8% and 81.2% for the memantine ER/ChEI- and placebo/ChEI groups, respectively. Memantine ER/ChEI-treated patients significantly outperformed placebo/ChEI-treated patients (LOCF) on the SIB (P=0.001), CIBIC-Plus (P=0.008), NPI (P=0.005), and VF (P=0.004); the effect was not significant on ADCS-ADL19 (P=0.177). The AEs with a frequency of ¡Ý5.0% in either group that were more prevalent in the memantine ER/ChEI group were headache (5.6% vs 5.1%) and diarrhea (5.0% vs 3.9%). Conclusions: Once-daily memantine ER capsules (28 mg) are an effective, safe, and well-tolerated therapy for patients with moderate to severe AD receiving stable ChEI treatment.