A Study to Evaluate the Efficacy and Safety of Two Dose Strengths of Dalfampridine Extended Release Tablets.

Study Overview
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Brief Summary
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The objective of this study is to determine the effect of two dose strengths of dalfampridine-Extended Release (ER) tablets, taken twice daily for 12 weeks, on stable walking deficits in subjects with post-ischemic stroke.

Detailed Description
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This was a randomized, placebo-controlled, three-arm, parallel-group study designed to evaluate the efficacy, safety, and tolerability of dalfampridine extended release (ER) tablets on chronic walking deficits in subjects with post-ischemic stroke.

Official Title
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This is a Multi-center, Double-blind, Three Arm, Parallel Group, Placebo-controlled, Randomized Study Designed to Evaluate the Efficacy, Safety and Tolerability of Dalfampridine.

Conditions
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Post-Ischemic Stroke

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical evidence of a stable walking deficit due to an ischemic stroke, as judged by the Investigator, based on review of medical records and physical exam. Such deficit was not present prior to the stroke and cannot be attributed primarily to other conditions (e.g. chronic obstructive pulmonary disease, arthritis). Evidence of walking deficits is objectively supported by any one of the following findings on clinical examination: obvious slowness of movement assigned primarily to the stroke use of an assistive walking device such as a cane or walker Presence of movement pattern deviations such as stiff-legged gait, foot drop, hip hiking and hip circumduction Modified Rankin Scale score of 1 - 3, regardless of the cause(s) of the disability Sufficient ambulatory ability to independently complete the 2MinWT and 10MWT ≥ 6 months from occurrence of most recent stroke Exclusion Criteria: Woman who is not surgically sterile or is less than 2 years postmenopausal, and does not agree to use a highly effective birth control method during the study and up to 3 months after the last dose of investigational product. Woman who is pregnant, breastfeeding, or planning to become pregnant History of seizures, except simple febrile seizures Moderate or severe renal impairment as defined by a calculated creatinine clearance of ≤ 50 mL/minute using the Cockcroft-Gault Equation Suicide attempt within 1 year prior to the Screening Visit, or severe suicidal ideation within 6 months prior to the Screening Visit, or subject is at significant risk of suicidal behavior in the opinion of the Investigator Previous use of AMPYRA, dalfampridine, fampridine or 4-aminopyridine (4-AP) Initiation of a serotonin reuptake inhibitor (SSRI) within 3 months prior to the Screening Visit, or any change in dosing regimen within 3 months prior to the Screening Visit Botulinum toxin use within 2 months prior to the Screening Visit Orthopedic surgical procedures in any of the extremities within the past 6 months

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects randomized 1:1:1 to receive either dalfampridine-ER 7.5mg, dalfampridine-ER 10mg, or matching placebo tablets taken twice daily 12 hours apart. | Drug: Placebo<br> <br> |
| Active Comparator: dalfampridine-ER 7.5 mg<br>Subjects randomized 1:1:1 to receive either dalfampridine-ER 7.5mg, dalfampridine-ER 10mg, or matching placebo tablets taken twice daily 12 hours apart. | Drug: dalfampridine-ER 7.5mg<br> <br> |
| Active Comparator: dalfampridine-ER 10mg<br>Subjects randomized 1:1:1 to receive either dalfampridine-ER 7.5mg, dalfampridine-ER 10mg, or matching placebo tablets taken twice daily 12 hours apart. | Drug: dalfampridine-ER 10mg<br> <br> * Other names: Ampyra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Show at Least a 20% Improvement on the Two Minute Walk Test (2MinWT) at Week 12 | The 2MinWT measures the distance a subject can walk in 2 minutes. Participants showing at Least a 20% Improvement on the 2MinWT at 12-weeks are considered Responders. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Walking Impact Scale (Walk-12) at Week 12 (Key Secondary) | 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) | Baseline, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post stroke, Ischemic stroke