This study assessed the efficacy and safety of ADS-5102 (at daily doses of 137 mg or 274 mg) compared with placebo in MS patients with walking impairment.
This was a multicenter, 3-arm, randomized, placebo-controlled, double-blind, parallel-group study of ADS-5102 (amantadine) extended release capsules in MS subjects with walking impairment. The study consisted of a screening period (up to 3 weeks), a single-blind placebo run-in period (4 weeks; during which subjects were blinded to treatment), and a double-blind treatment period (12 weeks). For at least 30 days prior to screening, all subjects were to have received a stable regimen of MS medications, both disease-modifying and symptomatic; these medications were to continue at the same doses and regimens for the duration of the subjects' participation in the study, to the extent compatible with good neurological care. Subjects were not to have used amantadine, dalfampridine, or any 4 aminopyridine or 2,4 diaminopyridine preparation within 30 days prior to screening. Consented subjects who completed the screening period were to undergo a 4-week single-blind placebo run-in period during which they received placebo as 2 capsules once daily at bedtime. Subjects who completed the single-blind placebo run-in period and continued to meet study eligibility criteria were randomized with equal probability to 1 of 3 treatment groups: placebo or ADS-5102 at a final dose of 137 mg/day or 274 mg/day. Study drugs were administered as 2 capsules once daily at bedtime. Subjects were to return to the clinic for safety and efficacy assessments at Week 0 and Week 2 prior to randomization and at Weeks 4 (randomization and baseline visit), 6 (only safety), 8, 12, and 16 after randomization. In addition, telephone visits for safety assessments were conducted at Weeks 5 and 7. Subjects who withdrew from the study before Week 16 were to have an early termination visit that included safety follow-up and efficacy assessments, as appropriate.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
558
Timed 25 Foot Walk (T25FW, Feet/Second): the Proportion of Subjects With a ≥ 20% Increase in Walking Speed (Measured by T25FW) From Baseline at Week 16 (Responder Analysis)
The T25FW is a measure of lower extremity function. The subject is directed to a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the subject walk back the same distance. For this outcome measure, the result is reported as speed (feet per second). Improvement is indicated by an increase in speed.
Time frame: 16 weeks
Timed 25 Foot Walk: Change From Baseline at Week 16
The T25FW is a measure of lower extremity function. The subject is directed to a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the subject walk back the same distance. For this outcome measure, the result is reported as or speed (feet per second). Improvement is indicated by an increase in speed.
Time frame: 16 weeks
Timed Up and Go (TUG): Change From Baseline at Week 16
The TUG is a measure of lower extremity strength, balance, and coordination. The subject stands up from a chair, walks 3 meters then turns around and walks back to the chair to sit down. The result is reported in seconds. Improvement is indicated by negative change scores.
Time frame: 16 weeks
2-Minute Walk Test (2MWT): Change From Baseline at Week 16
The 2MWT is a measure of lower extremity function. The subject is instructed to walk as far as possible in 2 minutes, and the distance is measured in meters. Improvement is indicated by positive change scores.
Time frame: 16 weeks
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