An Open Label, Proof of Concept Study to Evaluate the Effects of Dalfampridine Withdrawal on Gait and Balance Parameters in Subjects With Multiple Sclerosis (MS)

Study Overview
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Brief Summary
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The purpose of this study is to determine changes on overall gait as well as in multiple gait and balance parameters after withdrawal of dalfampridine-ER 10mg in MS subjects who are receiving the medication consistently for at least two weeks prior to screening.

Detailed Description
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Longitudinal study design

Official Title
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An Open-label, Proof of Concept Study to Evaluate Multiple Gait and Balance Parameters After Withdrawal of Dalfampridine-ER 10mg in Subjects With MS

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Withdrawal of dalfampridine-ER 10mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple sclerosis Receiving Ampyra® consistently for at least 2 weeks prior to the screening visit No history of seizures except simple febrile seizures Exclusion Criteria: Sexually active woman of childbearing potential who is not surgically sterile, <two years post-menopause or is not using effective birth control methods Subject who is pregnant or breastfeeding

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| dalfampridine-ER 10mg<br>Subjects with MS taking dalfampridine-ER 10mg and considered to be responders | Other: Withdrawal of dalfampridine-ER 10mg<br>* Withdrawal of dalfampridine-ER 10mg (7 days on study drug followed by withdrawal period of 10 days, followed by on study drug until study completion) On drug Day-7 (visit 1) through Day 1 (visit 2) Off drug Day 5±2 days (visit 3) through Day 11±2 days (visit 4) On drug Day 15±2 days (visit 5)<br>* Other names: Ampyra®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Score Overall Gait After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | The co-primary efficacy variable was overall gait. This novel composite score was created from standardized individual NeuroCom test results (Z-scores). ZGAIT (Z-Score Gait) is the average of Walk Across (WA) measuring step width, step length, speed; Tandem Walk (TW) measuring step width, speed and end sway, and Step/Quick turn (SQT) measuring turn time and turn sway). Overall gait was calculated by transforming ZGAIT into a percentile using the standard normal distribution. This rescales the Z-score to a scale from 0 to 100. A higher score is indicative of better performance. | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | 
| Composite Score Overall Balance After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | The co-primary efficacy variable was overall balance. This novel composite score was created from standardized individual NeuroCom test results (Z-scores). Overall balance is a weighted average of Sensory Organization Test (SOT) fixed surface eyes open, fixed surface eyes closed, walls moving eyes open, surface moving eyes open, surface moving eyes closed, surface and walls moving eyes open; Limits of Stability Test (LOS) measuring reaction time, movement velocity, endpoint excursion, maximum excursion and directional control; and Adaptation Test (ADT) measuring the averaged, raw sway and center of force during rotational disturbances. ZBAL (Z-Score Balance)= (ZSOT*0.5) + (ZADT*0.2) + (ZLOS*0.3) Overall balance was calculated by transforming ZBAL into a percentile using the standard normal distribution. This rescales the Z-score to a scale from 0 to 100. A higher score is indicative of better performance. | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on the Berg's Balance Scale (BBS) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | The BBS is a 14-item scale that evaluates subjects ability to sit, stand, reach, maintain single-leg stance, and turn. The scoring is rated from 0 (cannot perform task) to 4 (normal performance of task) for each of 14 items. The maximum possible score is 56 and the lowest 0. A higher total score is indicative of better performance. | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | 
| Change on the Two Minute Walk Test (2MWT) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | Subjects will walk without assistance for 2 minutes and the distance will be measured and timed by the use of a stop watch. A larger walking distance is indicative of better performance. | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | 
| Change on the Timed 25 Foot Walk Test (T25FW) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | The T25FW test is a measure of ambulatory function that provides quantitative data and is used widely in the MS population A higher walking speed is indicative of better performance | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, MS