Author Of 1 Presentation
P0225 - Phase 3 Study Results Assessing the Efficacy and Safety of ADS-5102 (Amantadine) Extended Release Capsules in MS Patients with Walking Impairment (ID 1919)
Abstract
Background
ADS-5102, FDA-approved as Gocovri, to treat dyskinesia in Parkinson’s disease, has a unique PK profile, such that once daily bedtime dosing provides higher amantadine concentrations from morning throughout the day and lower at night. Based on results from a 60-subject, 4-week, Phase-2 study, INROADS was designed to confirm benefit of ADS-5102 on walking in MS patients.
Objectives
To evaluate the efficacy and safety of ADS-5102 (amantadine) extended release capsules in patients with multiple sclerosis with walking impairment.
Methods
INROADS comprised a 4-week placebo run-in, followed by a 12-week double-blind period. Five hundred ninety-four MS patients with walking impairment from the US or Canada enrolled, and 560 were randomized, 1:1:1, to 274 mg ADS-5102 (n=185), 137 mg ADS-5102 (n=187), or placebo (n=186). The primary endpoint was the proportion of responders (≥20% improvement from baseline measured in ft/sec) in timed 25-foot walk [T25FW] at Week 16, comparing 274 mg ADS-5012 versus placebo. Subjects who did not have a Week 16 assessment were counted as non-responders. Additional outcomes included timed up and go test, 2-minute walk test, and MS walking scale-12. Prespecified subgroups, including prior dalfampridine use, were analyzed.
Results
Baseline characteristics were similar across treatment arms, with mean time since diagnosis 15.9 years, median EDSS 6.0, and mean T25FW 12.4 seconds; 52.5% reported prior dalfampridine use. At Week 16, 274 mg ADS-5102 demonstrated a statistically significantly greater response rate, 21.1% (P=.01) than placebo (11.3%); the response rate for 137 mg ADS-5102 was 17.6% (P=.08). For subjects who completed the study, the response rates were 28.3% (P< .001) for 274 mg, and 19.6% (P=.049) for 137 mg, vs. 11.9% for placebo. Response rates were consistent for subjects with (20.0%, 15.9%, vs. 11.0%) and without (22.5%, 19.2%, vs. 11.6%) prior dalfampridine use. The most commonly reported (>5%) adverse events (AEs) were peripheral edema, dry mouth, fall, constipation, UTI, and insomnia; AEs led to study drug discontinuation for 20.5% (274 mg), 6.4% (137 mg) and 3.8% (placebo) of subjects.
Conclusions
INROADS met its primary objective of showing clinically meaningful benefit in MS walking speed for 274 mg ADS-5102. A dose-response was seen for both efficacy and tolerability. AEs were consistent with the known safety profile of amantadine. Results suggest a role for ADS-5102 to improve walking in patients with MS, particularly those who have tried and discontinued dalfampridine.