Jeffrey A Cohen1, Samuel F Hunter2, Theodore R Brown3, Mark Gudesblatt4, Ben W Thrower5, Lily Llorens6, Cindy J Souza-Prien6, April E Ruby6, David N Chernoff6, Rajiv Patni6. 1. Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA. 2. Advanced Neuroscience Institute, Franklin, TN, USA. 3. Multiple Sclerosis Center, Evergreen Health, Kirkland, WA, USA. 4. Comprehensive Multiple Sclerosis Care Center, South Shore Neurologic Associates, P.C., Patchogue, NY, USA. 5. Crawford Research Institute, Shepherd Center, Atlanta, GA, USA. 6. Adamas Pharmaceuticals, Inc., Emeryville, CA, USA.
Abstract
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.
RCT Entities:
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-5102patients 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.
Authors: Jeffrey A Cohen; Michelle H Cameron; Myla D Goldman; Andrew D Goodman; Aaron E Miller; Anne Rollins; Lily Llorens; Rajiv Patni; Robert Elfont; Reed Johnson Journal: Mult Scler Date: 2021-08-27 Impact factor: 6.312