Grossberg_2013_CNS.Drugs_27_469

Reference

Title : The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer's disease taking cholinesterase inhibitors - Grossberg_2013_CNS.Drugs_27_469
Author(s) : Grossberg GT , Manes F , Allegri RF , Gutierrez-Robledo LM , Gloger S , Xie L , Jia XD , Pejovic V , Miller ML , Perhach JL , Graham SM
Ref : CNS Drugs , 27 :469 , 2013
Abstract :

INTRODUCTION: Immediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer's disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors.
METHODS: In this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3-14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran-Mantel-Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations.
RESULTS: A total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS-ADL19 (p = 0.177). Adverse events with a frequency of >/=5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9 %). CONCLUSION: Extended-release memantine was efficacious, safe, and well tolerated in this population.

PubMedSearch : Grossberg_2013_CNS.Drugs_27_469
PubMedID: 23733403

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Citations formats

Grossberg GT, Manes F, Allegri RF, Gutierrez-Robledo LM, Gloger S, Xie L, Jia XD, Pejovic V, Miller ML, Perhach JL, Graham SM (2013)
The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer's disease taking cholinesterase inhibitors
CNS Drugs 27 :469

Grossberg GT, Manes F, Allegri RF, Gutierrez-Robledo LM, Gloger S, Xie L, Jia XD, Pejovic V, Miller ML, Perhach JL, Graham SM (2013)
CNS Drugs 27 :469