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P3‐418: Evaluation of the efficacy and safety of the HSD‐1 inhibitor ABT‐384 in mild‐to‐moderate Alzheimer's disease
Author(s) -
Marek Gerard,
Katz David,
Meier Andreas,
Greco Nicholas,
Zhang Wuyan,
Liu Wei,
Lenz Robert
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.2092
Subject(s) - placebo , medicine , adverse effect , dementia , clinical endpoint , concordance , clinical trial , randomized controlled trial , interim analysis , disease , gastroenterology , pathology , alternative medicine
elderly volunteers. Methods: This randomized, double-blind, placeboand active-controlled Phase 2 study targeted enrollment of 260 subjects with mild-to-moderate AD (Mini-Mental Status Examination [MMSE] score of 10-24 inclusive) in Russia and Ukraine. Subjects not currently receiving anti-dementia medication were randomized to receive ABT-288 1 mg or 3 mg QD, donepezil 10 mg QD, or placebo for 12 weeks. The primary endpoint was the change from baseline to final evaluation in the 13-item Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score. Interim efficacy evaluations were performed to determine if ABT288 doses met predefined stopping criteria for futility. Adverse events (AEs), vital signs, ECG, and laboratory results were monitored. Results: The study was terminated for futility when 242 subjects were randomized and 153 (63.2%) had completed treatment. Twenty-one (8.7%) subjects discontinued prior to study termination. Subjects had a mean (SD) age of 70.2 (8.32) years and baseline MMSE of 18.0 (3.99). ABT-288 did not significantly improve performance on the ADAS-Cog (LS mean change 1⁄4 -0.54 and -1.14 for ABT-288 1mg [n1⁄4 52], and 3mg [n1⁄4 50], respectively) compared to placebo (-1.64, n 1⁄4 56). The LS mean change from baseline was significantly improved by donepezil (-4.32, n 1⁄4 54) compared to placebo (p 1⁄4 0.008), indicating adequate assay sensitivity. The percentage of subjects who reported 1 AE was similar among ABT-288 1 mg (54%), 3 mg, (39.3%) and placebo (39.7%) groups. Most AEs were mild or moderate in severity. Of AEs reported most frequently in subjects receiving ABT-288, anxiety (8.4%), dizziness (5.9%), agitation, irritability, and asthenia (each 5.0%) occurred more frequently than placebo. No clinically meaningful effects were observed for other safety measures. Conclusions: ABT-288 was not efficacious in subjects with mild-to-moderate AD, but was safe and well tolerated. The study design and execution achieved adequate assay sensitivity, evidenced by the significant improvement by donepezil.