Study of Fampridine-ER Tablets in Patients With Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Dalfampridine-ER 5mg; Dalfampridine-ER 10mg; Placebo
Intervention description: 5mg, twice daily; 10mg, twice daily; placebo, twice daily
Intervention MeSH terms: 4-Aminopyridine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 430.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to investigate the safety and efficacy of a lower dose of
      dalfampridine extended release tablets compared to the currently approved dose in improving
      walking in Multiple Sclerosis (MS) patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient has clinically definite Multiple Sclerosis as defined by the MacDonald
             Criteria.

          -  Patient must be 18 to 70 years of age, inclusive (i.e. on or after their 18th
             birthday, up to the day before their 71st birthday at the Screening Visit).

          -  Patient who has previously taken Ampyra® or dalfampridine (fampridine or 4
             aminopyridine; 4-AP) in any formulation (including compounded), must have withdrawn
             from the drug for at least one month prior to the Screening Visit.

          -  Patient must be mentally competent to understand and sign the Internal Review Board
             (IRB)-approved informed consent prior to the performance of any study-specific
             procedures.

          -  Patient is able to perform all the required study procedures.

          -  In the judgement of the Investigator, the patient has MS-related walking impairment
             but has sufficient ambulatory ability to be able to complete two trials of the Timed
             25 Foot Walk (T25FW) at the screening Visit and every study visit thereafter, with the
             two trials completed within 5 minutes of one another and in accordance with the
             specific instructions provided by the National Multiple Sclerosis Society MS
             Functional Composite Manual.

          -  Patient who is female and of childbearing potential (see Exclusion Criterion 1 for
             definition) must have a negative urine pregnancy test at the Screening Visit.

        Exclusion Criteria:

          -  Patient is a female of childbearing potential (i.e., has not had a hysterectomy or
             bilateral oophorectomy, or is not at least two years postmenopausal), engaged in
             active heterosexual relations and is not using one of the following birth control
             methods: tubal ligation, implantable contraception device, oral, patch or injectable
             contraceptive, double barrier method, or sexual activity restricted to vasectomized
             partner.

          -  Patient is pregnant or breastfeeding.

          -  Patient has any history of seizures.

          -  Patient has moderate or severe renal impairment as defined by a calculated creatinine
             clearance of ≤ 50 mL/minute.

          -  Patient has active urinary tract infection (UTI) at Screening or within the 4 weeks
             before Screening.

          -  Patient has had an onset (as assessed by the treating physician) of an MS exacerbation
             within 60 days prior to the Screening Visit.

          -  Patient has started on a concomitant prescription medication regimen within the last
             three weeks, and/or their concomitant medication regimen is expected to change during
             the course of the study.

          -  Patient has received cyclophosphamide (Cytoxan) or mitoxantrone (Novantrone) for MS
             treatment within six months prior to the Screening Visit.

          -  Patient has started a treatment regimen of Betaseron, Avonex, Copaxone, Rebif,
             Tysabri, Extavia or Gilenya™ within 90 days prior to the Screening Visit or has had
             any change in the dosing regimen of these drugs within 30 days prior to the Screening
             Visit.

          -  Patient has received corticosteroids (other than topical preparations) within 30 days
             prior to the Screening Visit and/or is expected to receive regularly scheduled
             corticosteroid treatment during the course of the study.

          -  Patient has been administered botulinum toxin in the lower extremities within six
             months prior to the Screening Visit and/or is expected to receive botulinum toxin in
             the lower extremities during the course of the study.

          -  Patient has a known allergy to pyridine-containing substances or any of the inactive
             ingredients of the dalfampridine tablet (colloidal silicon dioxide, hydroxypropyl
             methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol,
             and titanium dioxide).

          -  Patient has a history of drug or alcohol abuse within the past year.

          -  Patient has clinically significant abnormal laboratory values.

          -  Patient has angina, uncontrolled hypertension, clinically significant cardiac
             arrhythmias, or any other clinically significant cardiovascular abnormality.

          -  Patient has any medical condition (including psychiatric disease)that would interfere
             with the interpretation of the study results or the conduct of the study.

          -  Patient has participated in an investigational trial 30 days prior to Screening Visit
             or plans to enroll in another investigational trial at any time during this study.
             Non-drug (i.e. observational, registry) and non- medical device trials are allowed.