Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease.
Alzheimer Dis Assoc Disord
; 29(3): 192-9, 2015.
Article
en En
| MEDLINE
| ID: mdl-25973909
ABSTRACT
ABT-089, an α4ß2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian response-adaptive randomization algorithm dynamically assigned allocation probabilities based on interim ADAS-Cog total scores. A normal dynamic linear model for dose-response relationships and a longitudinal model for predicting final ADAS-cog score were employed in the algorithm. Stopping criteria for futility or success were defined. The futility stopping criterion was met, terminating the study with 337 patients randomized. No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all dose levels. When administered as adjunctive therapy to acetylcholinesterase inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease. The adaptive study design enabled the examination of a broad dose range, enabled rapid determination of futility, and reduced patient exposure to nonefficacious doses of the investigational compound.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piridinas
/
Pirrolidinas
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Inhibidores de la Colinesterasa
/
Cognición
/
Enfermedad de Alzheimer
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Límite:
Aged
/
Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Alzheimer Dis Assoc Disord
Asunto de la revista:
NEUROLOGIA
/
PSIQUIATRIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos