Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study
| Autor: | Gary E. Landreth, Suzanne Craft, Ülla Linnamägi, Sally Egginton, Sharon Sawchak, Marina Zvartau-Hind, Claire Alderton, Michael Gold, Ann M. Saunders, Michael C. Irizarry |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Agonist Apolipoprotein E medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions Genotype medicine.drug_class Cognitive Neuroscience Phases of clinical research Pharmacology Placebo Gastroenterology Rosiglitazone Central nervous system disease Apolipoproteins E Piperidines Alzheimer Disease Internal medicine Interview Psychological medicine Edema Humans Hypoglycemic Agents Donepezil Original Research Article Alleles Aged Aged 80 and over Intelligence Tests business.industry Middle Aged medicine.disease PPAR gamma Psychiatry and Mental health Treatment Outcome Nasopharyngitis Indans Female Thiazolidinediones Cholinesterase Inhibitors Geriatrics and Gerontology Alzheimer's disease business medicine.drug |
| Zdroj: | Dementia and Geriatric Cognitive Disorders. 30:131-146 |
| ISSN: | 1421-9824 1420-8008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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