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Bapineuzumab for mild to moderate Alzheimer's disease in two global, randomized, phase 3 trials.
Vandenberghe, Rik; Rinne, Juha O; Boada, Mercè; Katayama, Sadao; Scheltens, Philip; Vellas, Bruno; Tuchman, Michael; Gass, Achim; Fiebach, Jochen B; Hill, Derek; Lobello, Kasia; Li, David; McRae, Tom; Lucas, Prisca; Evans, Iona; Booth, Kevin; Luscan, Gerald; Wyman, Bradley T; Hua, Lisa; Yang, Lingfeng; Brashear, H Robert; Black, Ronald S.
Afiliación
  • Vandenberghe R; University Hospitals Leuven, Department of Neurosciences, Alzheimer Research Centre KU Leuven, Herestraat 49, 3000, Leuven, Belgium. rik.vandenberghe@uzleuven.be.
  • Rinne JO; Turku PET Centre and Division of Clinical Neurosciences, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
  • Boada M; Fundació ACE, Barcelona Alzheimer Treatment and Research Center, Gran via de Carles III, 85 Bis, 08028, Barcelona, Spain.
  • Katayama S; Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
  • Scheltens P; Alzheimercentrum VUmc, Neurology, VU University Medical Center, PO Box 7057, 1007, MB, Amsterdam, Netherlands.
  • Vellas B; CHU Toulouse, Gérontopôle, 170 Avenue de Casselardit, TSA 40031, 31059, Toulouse, Cedex 9, France.
  • Tuchman M; Palm Beach Neurological Center, 3365 Burns Road, Suite 203, Palm Beach Gardens, FL, 33410, USA.
  • Gass A; Department of Neurology, University Hospital Mannheim, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
  • Fiebach JB; Center for Stroke Research Berlin (CSB), Charité Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.
  • Hill D; IXICO Ltd., The London Bioscience Innovation Centre, 4th Floor, Griffin Court, 15 Long Lane, London, EC1A 9PN, UK.
  • Lobello K; Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
  • Li D; Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
  • McRae T; Pfizer Inc., 235 East 42nd Street, New York, NY, 10017, USA.
  • Lucas P; Pfizer Global Research and Development (PGRD), 23-25 avenue Du Docteur Lannelongue, Paris, Île-De-France, 75014, France.
  • Evans I; Pfizer Ltd., Walton Oaks, Dorking Road, Tadworth, Surrey, KT20 7NS, UK.
  • Booth K; Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
  • Luscan G; Pfizer Global Research and Development (PGRD), 23-25 avenue Du Docteur Lannelongue, Paris, Île-De-France, 75014, France.
  • Wyman BT; Pfizer Inc., 7 Kings Highway, Groton, CT, 06340, USA.
  • Hua L; Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
  • Yang L; Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
  • Brashear HR; Janssen Alzheimer Immunotherapy Research & Development, LLC, 700 Gateway Boulevard, South San Francisco, CA, 94080, USA.
  • Black RS; Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
Alzheimers Res Ther ; 8(1): 18, 2016 May 12.
Article en En | MEDLINE | ID: mdl-27176461
BACKGROUND: Our objective was to evaluate the efficacy (clinical and biomarker) and safety of intravenous bapineuzumab in patients with mild to moderate Alzheimer's disease (AD). METHODS: Two of four phase 3, multicenter, randomized, double-blind, placebo-controlled, 18-month trials were conducted globally: one in apolipoprotein E ε4 carriers and another in noncarriers. Patients received bapineuzumab 0.5 mg/kg (both trials) or 1.0 mg/kg (noncarrier trial) or placebo every 13 weeks. Coprimary endpoints were change from baseline to week 78 on the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale and the Disability Assessment for Dementia. RESULTS: A total of 683 and 329 patients completed the current carrier and noncarrier trials, respectively, which were terminated prematurely owing to lack of efficacy in the two other phase 3 trials of bapineuzumab in AD. The current trials showed no significant difference between bapineuzumab and placebo for the coprimary endpoints and no effect of bapineuzumab on amyloid load or cerebrospinal fluid phosphorylated tau. (Both measures were stable over time in the placebo group.) Amyloid-related imaging abnormalities with edema or effusion were confirmed as the most notable adverse event. CONCLUSIONS: These phase 3 global trials confirmed lack of efficacy of bapineuzumab at tested doses on clinical endpoints in patients with mild to moderate AD. Some differences in the biomarker results were seen compared with the other phase 3 bapineuzumab trials. No unexpected adverse events were observed. TRIAL REGISTRATION: Noncarriers (3000) ClinicalTrials.gov identifier NCT00667810 ; registered 24 Apr 2008. Carriers (3001) ClinicalTrials.gov identifier NCT00676143 ; registered 2 May 2008.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Anticuerpos Monoclonales Humanizados Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male Idioma: En Revista: Alzheimers Res Ther Año: 2016 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Anticuerpos Monoclonales Humanizados Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male Idioma: En Revista: Alzheimers Res Ther Año: 2016 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido