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- Title
Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer's Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study.
- Authors
Gold, Michael; Alderton, Claire; Zvartau-Hind, Marina; Egginton, Sally; Saunders, Ann M.; Irizarry, Michael; Craft, Suzanne; Landreth, Gary; Linnamägi, Ülla; Sawchak, Sharon
- Abstract
Background/Aims: A phase II study of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone extended release (RSG XR) in mild-to-moderate Alzheimer's disease (AD) detected a treatment benefit to cognition in apolipoprotein E(APOE)-ε4-negative subjects. The current phase III study with prospective stratification by APOE genotype was conducted to confirm the efficacy and safety of RSG XR in mild-to-moderate AD. An open-label extension study assessed the long-term safety and tolerability of 8 mg RSG XR. Methods: This double-blind, randomized, placebo-controlled study enrolled 693 subjects. Within 2 APOE allelic strata (ε4-positive, ε4-negative), subjects were randomized (2:2:2:1) to once-daily placebo, 2 mg RSG XR, 8 mg RSG XR or 10 mg donepezil (control). Coprimary endpoints were change from baseline to week 24 in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score, and week 24 Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+). Results: At week 24, no significant differences from placebo in change from baseline in coprimary endpoints were detected with either the RSG XR dose in APOE-ε4-negative subjects or overall. For donepezil, no significant treatment difference was detected in ADAS-Cog; however, a significant difference was detected (p = 0.009) on the CIBIC+. Peripheral edema was the most common adverse event for 8 mg RSG XR (15%) and placebo (5%), and nasopharyngitis for 2 mg RSG XR (7%). Conclusion: No evidence of efficacy of 2 mg or 8 mg RSG XR monotherapy in cognition or global function was detected in the APOE-ε4-negative or other analysis populations. The safety and tolerability of RSG XR was consistent with its known pharmacology. Copyright © 2010 S. Karger AG, Basel
- Subjects
ALZHEIMER'S disease; CLINICAL trials; ENZYME inhibitors; HYPOGLYCEMIC agents; EVALUATION of medical care; RESEARCH funding; STATISTICS; THIAZOLES; DATA analysis; BLIND experiment; DRUG therapy
- Publication
Dementia & Geriatric Cognitive Disorders, 2010, Vol 30, Issue 2, p131
- ISSN
1420-8008
- Publication type
Article
- DOI
10.1159/000318845