Arbaclofen Extended-Release Tablets for the Treatment of Spasticity in Patients with Multiple Sclerosis: A Randomized, Placebo-Controlled Clinical Trial

Objective: Evaluate the efficacy and safety of arbaclofen extended-release (ER) tablets in patients with multiple sclerosis (MS)-related spasticity. Methods: In a multicenter, double-blind, placebo-controlled study, adults with MS-related spasticity were randomized to arbaclofen ER 40 mg/day, arbaclofen ER 80 mg/day, or placebo for 12 weeks. Co-primary end points were the change from baseline to Week 12 in Total Numeric-transformed Modified Ashworth Scale in the Most Affected Limb (TNmAS-MAL) score and the Clinical Global Impression of Change (CGIC) score. A hierarchical testing procedure was used to evaluate the co-primary end points; analyses for the 80 mg/day group were considered inferential only if the  arbaclofen ER 40 mg/day and placebo groups demonstrated a statistically significant difference ( P ≤0∙05) for both end points. Results: 536 patients were included in the study. At Week 12, the least squares (LS) mean change from baseline in TNmAS-MAL score was –1∙67 (95% confidence interval [CI]: –1∙97, –1∙36) and –1∙28 (95% CI: –1∙57, –0∙99) in the arbaclofen ER 40 mg/day and placebo groups, respectively (LS mean difference, –0∙39; P <0∙048). Improvements were seen in mean CGIC scores for both the arbaclofen ER 40 mg/day and placebo groups, however no statistically significant difference was observed between them (LS mean difference, –0∙10; P =0∙43). Most adverse events were of mild-moderate severity. Conclusions: Administration of arbaclofen ER 40 mg/day for 12 weeks significantly reduced MS-related spasticity compared with placebo. Although arbaclofen ER 40 mg/day improved CGIC scores, a significance difference from placebo was not observed. Trial Registration Details: ClinicalTrials.gov, NCT03290131. Funding Information: This study was sponsored by Osmotica Pharmaceuticals Inc. which is now RVL Pharmaceuticals, Inc. RVL Pharmaceuticals, Inc., in conjunction with the lead authors, participated in the design and interpretation of the studies. Declaration of Interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Okuda received personal compensation for consulting and advisory services from Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, Inc., TG Therapeutics, Viela Bio, Inc., and research support from Biogen and EMD Serono/Merck. Royalties received for intellectual property licensed by The Board of Regents of The University of Texas System. Dr. Kantor reports receiving consulting fees and honoraria from: AbbVie, Biogen, Bristol Myers-Celgene, Genentech, Janssen, Novartis, RVL Pharmaceuticals and Sanofi. Dr. Jaros is a paid consultant of RVL Pharmaceuticals, Inc. Dr. deVries is a full-time employee of RVL Pharmaceuticals, Inc. Dr. Hunter reports receiving grants or research studies from Alkermes, Adamas, Biogen, Bristol Myers-Celgene, EMD Serono, Genentech, Novartis, Sanofi; consulting fees and honoraria from: AbbVie, Biogen, EMD Serono, Genentech, Janssen, Novartis, Osmotica, Sanofi; and writing assistance from Novartis, RVL Pharmaceuticals, Sanofi, and Mallinckrodt. Ethics Approval Statement: The protocol was approved by the institutional review board or ethics committee at each participating study site. All subjects provided written informed consent prior to enrollment.