INVESTIGADORES
ALLEGRI Ricardo F.
artículos
Título:
The Safe, Tolerability, and Efficacy of Once-Daily Memantine (28mg): A multinational, randomized, placebo-controlled trial in patients with moderate to severe Alzheimer?s disease taking cholinesterase inhibitor.
Autor/es:
GROSSBERG GT, MANES F, ALLEGRI RF, GUTIERREZ ROBLEDO LM, GLOGER S, XIE L, MILLER ÑL, PERHACH JL, GRAHAM SM
Revista:
CNS DRUGS
Editorial:
ADIS INT LTD
Referencias:
Año: 2013 vol. 27 p. 469 - 478
ISSN:
1172-7047
Resumen:
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-tosevere AD concurrently taking cholinesterase inhibitors.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 baselineto-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?ADL); 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. A total of 677 patients were randomized to receive extended-release memantine (>342) or placebo(>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]; , CIBIC-Plus (>0.008), NPI (>0.005), and verbal fluency test (>0.004); the effect did not achieve significance on ADCS?ADL5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9 %). Extended-release memantine was efficacious, safe, and well tolerated in this population. 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-tosevere AD concurrently taking cholinesterase inhibitors.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 baselineto-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?ADL); 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 (>342) or placebo(>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]; >0.001), CIBIC-Plus (>0.008), NPI (>0.005), and verbal fluency test (>0.004); the effect did not achieve significance on ADCS?ADL>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 %). Extended-release memantine was efficacious, safe, and well tolerated in this population.