T. Vollmer, Dan Chen, P. Nance
Feb 12, 2013
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Neurology
Abstract
OBJECTIVE: This ongoing, Phase 3 trial is evaluating the efficacy and safety of 3 doses of arbaclofen placarbil (AP), compared with placebo, for treatment of spasticity in patients with multiple sclerosis (MS). BACKGROUND: An estimated 80% of MS patients have spasticity, which can severely impair function. Baclofen, a racemate (mixture of R- and S- isomers), is a well-established spasticity treatment but is sometimes intolerable and requires frequent dosing (short half-life). AP is a prodrug of R-baclofen formulated in a sustained-release tablet. A previous Phase 2 trial in spinal cord injury subjects with spasticity demonstrated that AP administered BID provided sustained efficacy and was well tolerated. DESIGN/METHODS: This randomized, double-blind, placebo-controlled, multicenter study enrolling MS subjects with a Maximum Ashworth Scale Score (MASS) of ≥2 in at least one muscle group in the lower extremities, an Expanded Disability Status Scale Score (EDSS) of 3.0-8.0, and a Spasticity Disability Rating (SDR) of ≥2. Following a 21-day washout of anti-spasticity drugs and a 7-day, single-blind placebo run-in, eligible subjects were randomized 1:1:1:1 to BID dosing with 15 mg, 30 mg, or 45 mg AP, or matching placebo, for 12 weeks. The co-primary endpoints are change from baseline at Week 10 in MASS (six hours post dose) and the Patient Global Impression of Change. RESULTS: Demographics of 182 randomized subjects (91% of targeted enrollment): mean (SD) age 52.5 (9.2), 62.6% women, and 90.1% white. Mean (SD) baseline values are 2.6 (0.74) for MASS (6 hours post dose in placebo run-in); 3.2 (0.81) for SDR; and 5.3 (1.50) for EDSS. Efficacy and safety results will be presented. CONCLUSIONS: This trial is designed to demonstrate whether BID AP can provide sustained relief of spasticity with good tolerability in MS patients. If successful, it could support further development of AP for treatment of spasticity. Supported by: XenoPort Inc. Disclosure: Dr. Vollmer has received personal compensation for activities with Genzyme Corporation, Acorda Therapeutics, Accelerated Cure Projects for MS, Bristol-Myers Squibb Company, Teva Neuroscience, Biogen Idec, Novartis, and Hoffman-LaRoche. Dr. Vollmer has received research support from Teva Neuroscience, Genzyme Corporation, Ono Pharmaceutical, Biogen Idec, Janssen, and the National Institutes of Health. Dr. Chen has received personal compensation for activities with XenoPort, Inc. Dr. Chen holds stock and/or stock options in XenoPort, Inc. Dr. Nance has received personal compensation for activities with XenoPort, Inc. Dr. Ellenbogen has received personal compensation for activities with XenoPort, Inc., Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc., Allergan, Inc., Novartis, GlaxoSmithKline, Inc. and Ipsen. Dr. Flitman has nothing to disclose. Dr. Garrison has nothing to disclose. Dr. Huddlestone has nothing to disclose. Dr. Huffman has nothing to disclose. Dr. Mayadev has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Patton has nothing to disclose. Dr. Thrower has received compensation from Teva Neuroscience, Bayer Pharmaceuticals Corporation, Serono Inc., Biogen Idec, Pfizer and Acorda Therapeutics as a consultant and/or speaker. Dr. Thrower received research support from Teva Neuroscience, Serono Inc., Biogen Idec, Sanofi-Aventis Pharmaceuticals, Genzyme Corporation, Genetec Inc. and Acorda Therapeutics. Dr. Lissin has received personal compensation for activities with XenoPort Inc. Dr. Lissin holds stock and/or stock options in XenoPort Inc.