Study to Evaluate the Long-Term Safety, Tolerability and Efficacy of Dalfampridine.

Study Overview
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Brief Summary
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This is an extension study to evaluate the long-term safety, tolerability, and efficacy of two dose strengths of dalfampridine-ER.

Detailed Description
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This is an extension study to evaluate the long-term safety, tolerability, and efficacy of two dose strengths of dalfampridine-ER twice daily tablets when administered for at least 12 months to subjects with chronic post-ischemic stroke walking deficits who have completed the controlled, double-blind Study DALF-PS-1016.

Official Title
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An Extension Study to Evaluate the Long-Term Safety, Tolerability and Efficacy of Dalfampridine Extended-Release Tablets. for the Treatment of Chronic Post-Ischemic Stroke Walking Deficits .

Conditions
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Post-ischemic Stroke

Intervention / Treatment
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* Drug: dalfampridine-ER 7.5 mg
* Drug: dalfampridine-ER 10 mg


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Completion of the DALF-PS-1016 study Providing informed consent to continue into the DALF-PS-1029 long-term extension study Sufficient ambulatory ability to independently complete the Two Minute Walk Test (2MinWT) and 10 Meter Walk Test (10MWT) at the time of enrollment into the extension study Key Exclusion Criteria: Seizures, new onset strokes (or other significant neurological event precluding long-term continuation) occurring during the antecedent DALF-PS-1016 study Calculated creatinine clearance of ≤ 50 mL/minute at the time of enrollment into the long-term extension study

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: dalfampridine-ER 7.5 mg<br>Dalfampridine-ER 7.5 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. | Drug: dalfampridine-ER 7.5 mg<br> <br> |
| Active Comparator: dalfampridine-ER 10 mg<br>Dalfampridine-ER 10 mg tablets taken orally twice daily, approximately 12 hours apart. Subjects who received active treatment in the antecedent core study will retain the dose assignment to which they were initially randomized (7.5 mg or 10 mg dalfampridine-ER tablets). Subjects who received placebo in the core study will be randomly assigned to receive 7.5 mg or 10 mg dalfampridine-ER tablets in this extension study. | Drug: dalfampridine-ER 10 mg<br> <br> * Other names: Ampyra™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Objective Was to Evaluate Serious and Non-serious Adverse Events for Study Participants as a Measure of Safety and Tolerability of Dalfampridine ER (Extended Release) for at Least 12-months. | This extension study was designed to evaluate long-term safety, tolerability, and efficacy of dalfampridine-ER (extended release) in adult subjects with chronic post-ischemic stroke walking deficits. Subjects who had completed the placebo-controlled DALF-PS-1016 core study were eligible to enroll regardless of whether they had received active drug or placebo in the core study. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Two-Minute Walk Test (2MinWT) | 2 Minute Walk Test (2MinWT) and Change from Baseline by Visit | Day 1, up to 12 months | 
| Change From Baseline on the 10 Meter Walk Test (10MWT) | 10 Meter Walk Test (10MWT) and Change from Baseline by Visit | Day 1, up to 12 months | 
| Change From Baseline on the Timed up and Go (TUG) Test | The TUG measures mobility and balance and can predict the risk of falls. This test, which was initially called the Get-up and Go test, is considered a measure of dynamic balance. The subject is asked to stand up from a chair, walk 10 feet at a comfortable pace, turn around and be seated. The Timed Up and Go (TUG) is measured in seconds. There will be one practice test and then the timed test. Only the timed test will be analyzed at each visit time point. Reciprocal transformation may be performed if the time values are markedly skewed. | Day 1, up to 12 months | 
| Change From Baseline on the Walking Impact Scale (Walk-12) | The Walk-12 is a 12-question questionnaire that asks subjects to rate limitations of their mobility during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). For each visit, the Walk-12 score will be calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. A higher score indicates a greater degree of limitation in walking. A negative change indicates an improvement in walking. 0 = no limitation in mobility to 100 extreme limitation in mobility. Walk-12 Score = 100 * [(Mean of the 12 items) - 1]/(5-1) | Day 1, up to 12 months | 
| Change From Baseline on the Stroke Impact Scale (SIS) | The SIS consists of 59 items grouped in 8 domains: strength, hand function, activities of daily living (ADL) / instrumental activities of daily living (IADL), mobility, communication, emotion, memory and thinking, and participation/role function. The subject is asked to rate the level of difficulty in performing each item in the preceding week. Each item is scored on a 5-point scale ranging from 1 (inability to complete the item) to 5 (no difficulty experienced at all). For each domain, the SIS score will be calculated by summing all the items within the domain and transforming into a scale with a range of 0 to 100 as follows: SIS Score = 100 * [(Actual raw score - Lowest possible raw score)/ (Highest possible raw score-Lowest possible raw score)]. | Day 1, up to 12 months | 
| Subject Global Impression (SGI) | The Subject Global Impression (SGI) is single item measure of treatment response that asks the subject to rate the effects of the investigational drug on his or her overall walking ability using a 7 point scale ranging from 1 = Terrible to 7 = Delighted. | Visit 8 (Month 12) | 
| Change From Baseline on the 12-item Health Survey (SF-12) | The SF-12 v2 (4-week recall) is a general health-related quality-of-life profile measure consisting of 12 items. The SF-12 Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores will be derived and normed to a general United States population for score algorithm. The normalized PCS and MCS scores will be calculated at baseline, Month 12, and subsequent visits. SF-12 is a Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Day 1, up to 12 months |