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\nADS-5102, a delayed-release, extended-release (DR/ER) amantadine, improved walking speed in MS in a Phase 2 trial.\n\n\nOBJECTIVE\nThe aim of this study was to present primary results of a Phase 3, double-blind, ADS-5102 trial (INROADS) for walking speed.\n\n\nMETHODS\nAdult 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\u2009mg/day ADS-5102 for 12\u2009weeks. Primary outcome was the proportion of responders (20% increase in Timed 25-Foot Walk (T25FW) speed) for 274\u2009mg 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).\n\n\nRESULTS\nIn total, 558 participants were randomized and received double-blind treatment. Significantly more participants responded with 274\u2009mg ADS-5102 (21.1%) versus placebo (11.3%). Mean T25FW speed also significantly improved (0.19\u2009ft/s) versus placebo (0.07\u2009ft/s). Other measures were not significant using prespecified hierarchical testing procedure. Adverse events led to discontinuation for 3.8% (placebo), 6.4% (137\u2009mg ADS-5102), and 20.5% (274\u2009mg ADS-5102).\n\n\nCONCLUSION\nINROADS met its primary endpoint, showing a significantly greater proportion of participants with meaningful improvement in walking speed for 274\u2009mg ADS-5102 versus placebo. Numeric dose response was seen for some secondary efficacy outcomes and adverse events.