A Safety and Efficacy Study of ADS-5102 in Patients With Multiple Sclerosis and Walking Impairment

Study Overview
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Brief Summary
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This study assessed the long-term safety and tolerability of ADS-5102 in subjects with MS and walking impairment who had completed the double-blind, placebo-controlled study of ADS-5102 in subjects with MS (ADS-AMT-301).

Detailed Description
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This was a multicenter, open-label study of ADS-5102 (amantadine) extended-release capsules in subjects with MS and walking impairment who completed study drug treatment for 16 weeks and completed a Week 16 visit in Study ADS-AMT-MS301. All enrolled subjects were to receive ADS-5102 at 137 mg for the first week, 205.5 mg for the second week, and 274 mg for the remainder of the 52-week open-label treatment period. Subjects returned to the clinic for safety and efficacy assessments at Weeks 4, 24, and 52. In addition, a telephone visit for safety assessments was conducted at Week 2 and Week 38. Subjects who withdrew from the study prior to completion of the Week 52 visit had an early termination (ET) visit that included safety and efficacy assessments. Subjects who completed 52 weeks of open-label treatment had a final visit for post-treatment safety follow-up and efficacy assessment at Week 54. All study visits and efficacy assessments were to be scheduled to occur at approximately the same time of day for each individual subject. Each subject's efficacy assessment was to be performed by the same clinical rater, if possible.

Official Title
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A Multicenter, Open-Label Safety and Efficacy Study of ADS-5102 Amantadine Extended Release Capsules in Patients With Multiple Sclerosis and Walking Impairment

Conditions
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Multiple Sclerosis, Walking Impairment

Intervention / Treatment
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* Drug: ADS-5102, 274 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed a current IRB-approved informed consent form Successful completion of a prior double blind study of ADS-5102 in patients with MS walking impairment. Exclusion Criteria: Based on the judgment of the investigator or Medical Monitor, participation in the study would jeopardize the safety of the subject. If female, is pregnant or lactating If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize a highly effective hormonal method of contraception (an IUD, or vasectomized male partner is also acceptable), in combination with a barrier method, from baseline through at least 4 weeks after the completion of study treatment. If a sexually active male, does not agree to utilize condoms from screening through at least 4 weeks after the completion of study treatment. Anticipated treatment with any amantadine formulation other than ADS-5102 Planned participation in another interventional clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADS-5102, 274 mg<br>274 mg ADS-5102, administered once daily at bedtime for up to 52 weeks | Drug: ADS-5102, 274 mg<br>* Oral capsules<br>* Other names: amantadine extended release;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events | The incidence of treatment-emergent adverse events was used as the measure for long-term safety and tolerability of ADS-5102. | Through study completion, an average of 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timed 25-Foot Walk (Feet/Second) (Baseline Value) | The timed 25-foot walk 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. The result is reported as speed (feet per second). Improvement is indicated by an increase in speed. | Baseline | 
| Timed 25-Foot Walk (Feet/Second) (Week 24 Value) | The timed 25-foot walk 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. The result is reported as speed (feet per second). Improvement is indicated by an increase in speed. | 24 weeks | 
| Timed 25-Foot Walk (Feet/Second) (Week 52 Value) | The timed 25-foot walk 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. The result is reported as speed (feet per second). Improvement is indicated by an increase in speed. | 52 weeks | 
| Timed up and go (Baseline Value) | The timed up and go 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. | Baseline | 
| Timed up and go (Week 24 Value) | The timed up and go 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. | 24 weeks | 
| Timed up and go (Week 52 Value) | The timed up and go 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. | 52 weeks | 
| 2-Minute Walk Test (Baseline Value) | The 2-Minute Walk test 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. | Baseline | 
| 2-Minute Walk Test (Week 24 Value) | The 2-Minute Walk test 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. | 24 weeks | 
| 2-Minute Walk Test (Week 52 Value) | The 2-Minute Walk test 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. | 52 weeks |