A Placebo Controlled Trial of Dalfampridine ER for Ambulatory Activity in People With Multiple Sclerosis

Phase 4

Completed

Brief Summary: A randomized placebo controlled double-blind cross-over trial of Dalfampridine ER for effect on ambulatory activity in people with multiple sclerosis

Detailed Description: This is a parallel-group, double-blind, randomized controlled crossover trial with a 1:1 randomization. There are two treatment periods of 4 weeks and a two-week off treatment washout period. Treatment periods are DER (dalfampridine ER) followed by placebo (group A) and placebo followed by DER (group B), respectively. All dosages will be administered twice a week. Purpose of the study is to see if using the study drug(dalfampridine Er) for a short period of time will improve the way subjects with multiple sclerosis (MS) walk.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of MS made at least 3 months prior to based McDonald or Proser criteria.
Age 18-75 years old inclusive.
Expanded Disability Status Scale (EDS) 0-6.5
Clinical stability defined as no MS exacerbation or change in disease modifying therapy for 60 days prior to screening.
Screening 6-minute walking test distance between 50m-500m, inclusive.
Written informed consent.

Exclusion Criteria

use of 4-aminopyridine within 6 months of screening
Any contraindication to DER:
- Allergy to DER
- history of seizure disorder or history of EEG showing epileptiform activity
- Renal insufficiency (estimated GFR < 60.
Any condition that would exclude 6 minute walking testing:
- Cardiac surgery or myocardial infarction within the last 3 months.
- Severe aortic stenosis or hypertropic cardiomyopathy.
- Pulmonary embolus or infarction in the last 6 months.
- Uncontrolled hypertension by history or by screening or baseline diastolic blood pressure > 170, or systolic blood pressure > 105.
- Use of oxygen at home for 24 hours/day or severe lung disease.
History of ventricular arrhythmia or finding of significant ventricular arrhythmia. atrial arrhythmia or 2nd or 3rd degree heart block on screening ECG.
Concomitant neurological disease, such as ALS, Parkinson Disease, stroke.
Hospitalization in the last 6 months for psychiatric illness.
Alcohol or drug abuse within the past year.
Females who are breast-feeding, pregnant or have potential to become pregnant during the course of the study( fertile and unwilling/unable to use effective contraceptive measures)
Cognitive deficits that would interfere with the subject's ability to give informed consent or preform study testing.
Any other serious and/or unstable medical condition.
Use of mitoxantrone (Novantrone) within 6 months of baseline visit.

Arm && Interventions

Group	Intervention	Description
dalfampridine ER 10mg bid-placebo	dalfampridine ER	4 week administration of dalfampridine ER 10mg bid followed by 2 week washout and 4 weeks of placebo control
dalfampridine ER 10mg bid-placebo	placebo	4 week administration of dalfampridine ER 10mg bid followed by 2 week washout and 4 weeks of placebo control
placebo-dalfampridine ER 10mg bid	dalfampridine ER	placebo tablet administered bid for four weeks followed by 2 week washout and 4 weeks of dalfampridine ER 10mg bid
placebo-dalfampridine ER 10mg bid	placebo	placebo tablet administered bid for four weeks followed by 2 week washout and 4 weeks of dalfampridine ER 10mg bid

Primary Outcome Measures

Name	Time	Method
Peak Activity Index	10 weeks	peak activity index is a measure of the 30 fastest minutes of walking over a 24 hour period, averaged over one week of accelerometer wear. Measurement is change from baseline to 4 weeks on intervention

Secondary Outcome Measures