(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 Alzhei mer'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-4 -negative subjects or overall. For donepezil, no significant treatment difference was detected in ADASCog; 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-4 -negative or other analysis populations. The safety and tolerability of RSG XR was consistent with its known pharmacology.Copyright © 2010 S. Karger AG, Basel Key WordsRosiglitazone, extended release ؒ Monotherapy ؒ Alzheimer's disease ؒ Peroxisome proliferator-activated receptor-␥ ؒ Cognition ؒ Apolipoprotein E allele 4 ؒ Health outcomes ؒ Donepezil Abstract Background/Aims: A phase II study of the peroxisome proliferator-activated receptor-␥ agonist rosiglitazone extended release (RSG XR) in mild-to-moderate Alzheimer's disease (AD) detected a treatment benefit to cognition in apolipoprotein E ( APOE )-4 -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 ( 4 -positive, 4 -negative), subjects were randomized

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No evidence of statistically or clinically significant efficacy in cognition or global function was detected for 2 mg or 8 mg RSG XR as adjunctive therapy to ongoing AChEIs. There was no evidence of an interaction between treatment and APOE status. Safety and tolerability of RSG XR was consistent with the known profile of rosiglitazone.

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