Safety and efficacy of ADS-5102 (amantadine) extended release capsules to improve walking in multiple sclerosis: A randomized, placebo-controlled, phase 2 trial.
BACKGROUND
Walking impairment causes disability and reduced quality of life in patients with multiple sclerosis (MS).


OBJECTIVE
Characterize the safety and efficacy of ADS-5102 (amantadine) extended release capsules, 274 mg administered once daily at bedtime in patients with MS with walking impairment.


METHODS
This randomized, double-blind, placebo-controlled, 4-week study was conducted at 14 trial sites in the United States. Study objectives included safety and tolerability of ADS-5102, and efficacy assessments (Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), 2-Minute Walk Test, and Multiple Sclerosis Walking Scale-12). Fatigue, depression, and cognition also were assessed.


RESULTS
A total of 60 patients were randomized (30 to ADS-5102 and 30 to placebo); 59 of whom were treated. The most frequent adverse events (AEs) were dry mouth, constipation, and insomnia. Five ADS-5102 patients and no placebo patients discontinued treatment due to AEs. One patient in the ADS-5102 group experienced a serious AE-suspected serotonin syndrome. A 16.6% placebo-adjusted improvement was seen in the T25FW test ( p < 0.05). A 10% placebo-adjusted improvement in TUG was also observed. No changes in fatigue, depression, or cognition were observed.


CONCLUSION
ADS-5102 was generally well tolerated. These data demonstrate an effect of ADS-5102 on walking speed. Further studies are warranted to confirm these observations.
['Cohen|Jeffrey A|JA|', 'Hunter|Samuel F|SF|', 'Brown|Theodore R|TR|', 'Gudesblatt|Mark|M|', 'Thrower|Ben W|BW|', 'Llorens|Lily|L|', 'Souza-Prien|Cindy J|CJ|', 'Ruby|April E|AE|', 'Chernoff|David N|DN|', 'Patni|Rajiv|R|']
D000328:Adult D000368:Aged D000547:Amantadine D003692:Delayed-Action Preparations D015259:Dopamine Agents D004311:Double-Blind Method D020820:Dyskinesias D005080:Exercise Test D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D009103:Multiple Sclerosis D017063:Outcome Assessment, Health Care D000075082:Proof of Concept Study D016138:Walking
ADS-5102 amantadine walking Multiple sclerosis walking impairment MS walking speed