Tags

Type your tag names separated by a space and hit enter

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.

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.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Neurology and Psychiatry, Saint Louis University School of Medicine, 1438 S. Grand Boulevard, St. Louis, MO 63104, USA. grossbgt@slu.edu

    , , , , , , , , ,

    Source

    CNS drugs 27:6 2013 Jun pg 469-78

    MeSH

    Aged
    Alzheimer Disease
    Argentina
    Cholinesterase Inhibitors
    Delayed-Action Preparations
    Dose-Response Relationship, Drug
    Double-Blind Method
    Drug Administration Schedule
    Drug Therapy, Combination
    Excitatory Amino Acid Antagonists
    Female
    Humans
    Male
    Memantine
    Mexico
    Severity of Illness Index
    Treatment Outcome
    United States

    Pub Type(s)

    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23733403

    Citation

    Grossberg, George T., et al. "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, vol. 27, no. 6, 2013, pp. 469-78.
    Grossberg GT, Manes F, Allegri RF, et al. 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. 2013;27(6):469-78.
    Grossberg, G. T., Manes, F., Allegri, R. F., Gutiérrez-Robledo, L. M., Gloger, S., Xie, L., ... Graham, S. M. (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(6), pp. 469-78. doi:10.1007/s40263-013-0077-7.
    Grossberg GT, et al. 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. 2013;27(6):469-78. PubMed PMID: 23733403.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Grossberg,George T, AU - Manes,Facundo, AU - Allegri,Ricardo F, AU - Gutiérrez-Robledo,Luis Miguel, AU - Gloger,Sergio, AU - Xie,Lei, AU - Jia,X Daniel, AU - Pejović,Vojislav, AU - Miller,Michael L, AU - Perhach,James L, AU - Graham,Stephen M, PY - 2013/6/5/entrez PY - 2013/6/5/pubmed PY - 2014/1/15/medline SP - 469 EP - 78 JF - CNS drugs JO - CNS Drugs VL - 27 IS - 6 N2 - 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. SN - 1179-1934 UR - https://www.unboundmedicine.com/medline/citation/23733403/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_ L2 - https://dx.doi.org/10.1007/s40263-013-0077-7 DB - PRIME DP - Unbound Medicine ER -