@article{6df3dc9aae82450196b3173ae8faec83,
title = "A Phase 3, double-blind, placebo-controlled efficacy and safety study of ADS-5102 (Amantadine) extended-release capsules in people with multiple sclerosis and walking impairment",
abstract = "Background: ADS-5102, a delayed-release, extended-release (DR/ER) amantadine, improved walking speed in MS in a Phase 2 trial. Objective: The aim of this study was to present primary results of a Phase 3, double-blind, ADS-5102 trial (INROADS) for walking speed. Methods: Adult participants with MS and walking impairment, not currently using amantadine or dalfampridine, underwent 4-week placebo run-in before randomization 1:1:1 to placebo, 137 or 274 mg/day ADS-5102 for 12 weeks. Primary outcome was the proportion of responders (20% increase in Timed 25-Foot Walk (T25FW) speed) for 274 mg ADS-5102 versus placebo at end of double-blind (Study Week 16). Additional measures included Timed Up and Go (TUG), 2-Minute Walk Test (2MWT), and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Results: In total, 558 participants were randomized and received double-blind treatment. Significantly more participants responded with 274 mg ADS-5102 (21.1%) versus placebo (11.3%). Mean T25FW speed also significantly improved (0.19 ft/s) versus placebo (0.07 ft/s). Other measures were not significant using prespecified hierarchical testing procedure. Adverse events led to discontinuation for 3.8% (placebo), 6.4% (137 mg ADS-5102), and 20.5% (274 mg ADS-5102). Conclusion: INROADS met its primary endpoint, showing a significantly greater proportion of participants with meaningful improvement in walking speed for 274 mg ADS-5102 versus placebo. Numeric dose response was seen for some secondary efficacy outcomes and adverse events.",
keywords = "2-Minute Walk Test, Multiple Sclerosis Walking Scale-12, Multiple sclerosis, Timed 25-Foot Walk, Timed Up and Go, amantadine, randomized controlled trial",
author = "Cohen, {Jeffrey A.} and Cameron, {Michelle H.} and Goldman, {Myla D.} and Goodman, {Andrew D.} and Miller, {Aaron E.} and Anne Rollins and Lily Llorens and Rajiv Patni and Robert Elfont and Reed Johnson",
note = "Funding Information: The authors thank the INROADS investigators, study staff, and patients for their contributions to the research presented in this paper. Editorial assistance was provided by Robin Smith, PhD, of The Curry Rockefeller Group, LLC (Tarrytown, NY), and was funded by Adamas Pharmaceuticals, Inc. Andrea E. Formella, PharmD, and Judy Lytle, PhD, provided editorial assistance, data QC, and project management. Rob Howard of Veridical Solutions provided data analysis services. Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.A.C. has received personal compensation for consulting for Adamas, Atara, Bristol Myers Squibb, Convelo, MedDay, and Mylan and for serving as an editor of Multiple Sclerosis Journal. M.H.C. has received personal compensation as a consultant for Adamas, Greenwich Biosciences, MedLink, and Helius Medical Technologies. M.D.G. has served as a consultant for Adamas, Biogen Idec, Brainstorm Cell Therapeutics Ltd., EMD Serono, Genentech, Greenwich Biosciences, Immunic, MedDay, and Sanofi Genzyme; she is funded by National MS Society Grant RG-2004-36580. A.D.G. has received consulting fees from Adamas, Greenwich Biosciences, and SwanBio; his employer has received research support from Biogen and Sanofi Genzyme. A.E.M. has served as a consultant for AbbVie, Caremark, Adamas, Biogen Idec, Bristol Myers Squibb/Celgene, Corrona, EMD Serono, Mapi-Pharma, Mylan, Novartis, and Roche/Genentech; he has received research support from Genzyme/Sanofi, Novartis, Roche/Genentech, and MedDay, and is on the speaker{\textquoteright}s bureau (providing unbranded programs only) at EMD Serono (journal club), Alexion, Biogen Idec, and Genentech (disease awareness programs). A.R. and R.J. are employees and own stock in Adamas Pharmaceuticals, Inc. L.L. is a former employee of, and currently receives personal compensation as a consultant for Adamas Pharmaceuticals. R.P. and R.E. are former employees of and own stock in Adamas Pharmaceuticals. Publisher Copyright: {\textcopyright} The Author(s), 2021.",
year = "2022",
month = apr,
doi = "10.1177/13524585211035333",
language = "English (US)",
volume = "28",
pages = "817--830",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "5",
}