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 t...

Autores
Grossberg, George T.; Manes, Facundo Francisco; Allegri, Ricardo Francisco; Gutiérrez Robledo, Luis Miguel; Gloger, Sergio; Xie, Lei; Jia, X. Daniel; Pejoviç, Vojislav; Miller, Michel L.; Perhach, James; Graham, Stephen M.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Grossberg, George T.. Saint Louis University School of Medicine; Estados Unidos
Fil: Manes, Facundo Francisco. Instituto de Neurología Cognitiva; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Allegri, Ricardo Francisco. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gutiérrez Robledo, Luis Miguel. Institutos Nacionales de Salud de México. Instituto de Geriatría; México
Fil: Gloger, Sergio. PsicoMedica Clinical and Research Group; Chile
Fil: Xie, Lei. Forest Research Institute; Estados Unidos
Fil: Jia, X. Daniel. Forest Research Institute; Estados Unidos
Fil: Pejoviç, Vojislav. Prescott Medical Communications Group; Estados Unidos
Fil: Miller, Michel L.. Prescott Medical Communications Group; Estados Unidos
Fil: Perhach, James. Forest Research Institute; Estados Unidos
Fil: Graham, Stephen M.. Forest Research Institute; Estados Unidos
Materia
Alzheimer
Memantine
Trial
Once-Daily
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24718
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/24718
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 inhibitorGrossberg, George T.Manes, Facundo FranciscoAllegri, Ricardo FranciscoGutiérrez Robledo, Luis MiguelGloger, SergioXie, LeiJia, X. DanielPejoviç, VojislavMiller, Michel L.Perhach, JamesGraham, Stephen M.AlzheimerMemantineTrialOnce-Dailyhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3INTRODUCTION: 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.Fil: Grossberg, George T.. Saint Louis University School of Medicine; Estados UnidosFil: Manes, Facundo Francisco. Instituto de Neurología Cognitiva; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Allegri, Ricardo Francisco. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gutiérrez Robledo, Luis Miguel. Institutos Nacionales de Salud de México. Instituto de Geriatría; MéxicoFil: Gloger, Sergio. PsicoMedica Clinical and Research Group; ChileFil: Xie, Lei. Forest Research Institute; Estados UnidosFil: Jia, X. Daniel. Forest Research Institute; Estados UnidosFil: Pejoviç, Vojislav. Prescott Medical Communications Group; Estados UnidosFil: Miller, Michel L.. Prescott Medical Communications Group; Estados UnidosFil: Perhach, James. Forest Research Institute; Estados UnidosFil: Graham, Stephen M.. Forest Research Institute; Estados UnidosSpringer2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24718Grossberg, George T.; Manes, Facundo Francisco; Allegri, Ricardo Francisco; Gutiérrez Robledo, Luis Miguel; Gloger, Sergio; et al.; 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; Springer; Cns Drugs; 27; 6; 6-2013; 469-4781172-70471179-1934CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs40263-013-0077-7info:eu-repo/semantics/altIdentifier/doi/10.1007/s40263-013-0077-7info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680656/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:15:20Zoai:ri.conicet.gov.ar:11336/24718instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:15:20.763CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 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
title 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
spellingShingle 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
Grossberg, George T.
Alzheimer
Memantine
Trial
Once-Daily
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
dc.creator.none.fl_str_mv Grossberg, George T.
Manes, Facundo Francisco
Allegri, Ricardo Francisco
Gutiérrez Robledo, Luis Miguel
Gloger, Sergio
Xie, Lei
Jia, X. Daniel
Pejoviç, Vojislav
Miller, Michel L.
Perhach, James
Graham, Stephen M.
author Grossberg, George T.
author_facet Grossberg, George T.
Manes, Facundo Francisco
Allegri, Ricardo Francisco
Gutiérrez Robledo, Luis Miguel
Gloger, Sergio
Xie, Lei
Jia, X. Daniel
Pejoviç, Vojislav
Miller, Michel L.
Perhach, James
Graham, Stephen M.
author_role author
author2 Manes, Facundo Francisco
Allegri, Ricardo Francisco
Gutiérrez Robledo, Luis Miguel
Gloger, Sergio
Xie, Lei
Jia, X. Daniel
Pejoviç, Vojislav
Miller, Michel L.
Perhach, James
Graham, Stephen M.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer
Memantine
Trial
Once-Daily
topic Alzheimer
Memantine
Trial
Once-Daily
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Grossberg, George T.. Saint Louis University School of Medicine; Estados Unidos
Fil: Manes, Facundo Francisco. Instituto de Neurología Cognitiva; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Allegri, Ricardo Francisco. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gutiérrez Robledo, Luis Miguel. Institutos Nacionales de Salud de México. Instituto de Geriatría; México
Fil: Gloger, Sergio. PsicoMedica Clinical and Research Group; Chile
Fil: Xie, Lei. Forest Research Institute; Estados Unidos
Fil: Jia, X. Daniel. Forest Research Institute; Estados Unidos
Fil: Pejoviç, Vojislav. Prescott Medical Communications Group; Estados Unidos
Fil: Miller, Michel L.. Prescott Medical Communications Group; Estados Unidos
Fil: Perhach, James. Forest Research Institute; Estados Unidos
Fil: Graham, Stephen M.. Forest Research Institute; Estados Unidos
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/24718
Grossberg, George T.; Manes, Facundo Francisco; Allegri, Ricardo Francisco; Gutiérrez Robledo, Luis Miguel; Gloger, Sergio; et al.; 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; Springer; Cns Drugs; 27; 6; 6-2013; 469-478
1172-7047
1179-1934
CONICET Digital
CONICET
url http://hdl.handle.net/11336/24718
identifier_str_mv Grossberg, George T.; Manes, Facundo Francisco; Allegri, Ricardo Francisco; Gutiérrez Robledo, Luis Miguel; Gloger, Sergio; et al.; 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; Springer; Cns Drugs; 27; 6; 6-2013; 469-478
1172-7047
1179-1934
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs40263-013-0077-7
info:eu-repo/semantics/altIdentifier/doi/10.1007/s40263-013-0077-7
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680656/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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