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

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.

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.