Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of Two Doses of Oral Dalfampridine Extended Release Tablets (5 mg and 10 mg Twice Daily) in Patients With Multiple Sclerosis
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Multiple Sclerosis
- Sponsor
- Acorda Therapeutics
- Enrollment
- 430
- Locations
- 69
- Primary Endpoint
- Change From Baseline in Walking Speed Near Maximum Plasma Concentration at Steady State (CmaxSS) of Placebo and Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW).
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief 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.
Detailed Description
The current study is designed as a prospective placebo-controlled trial to investigate the safety and efficacy of a lower dose of dalfampridine extended release tablets (5 mg twice daily) compared to the approved commercial dose of 10 mg twice daily in improving walking in MS patients during a four-week period of treatment.
Investigators
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Ampyra® or dalfampridine (fampridine or 4 aminopyridine; 4-AP) in any formulation (including compounded), must have withdrawn from the drug for at least one month prior to the Screening Visit.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.
Arms & Interventions
Placebo
placebo, twice daily
Intervention: Placebo
Dalfampridine-ER 5mg
5mg, twice daily
Intervention: Dalfampridine-ER 5mg
Dalfampridine-ER 10mg
10mg, twice daily
Intervention: Dalfampridine-ER 10mg
Outcomes
Primary Outcomes
Change From Baseline in Walking Speed Near Maximum Plasma Concentration at Steady State (CmaxSS) of Placebo and Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW).
Time Frame: Baseline Visit 1 (double-blind study day 1) and approximately 3-4 hours post dose at Visit 3 (end of double-blind week 4)
The T25FW test is a quantitative measure of ambulatory function that is widely used by MS specialists to assess the global impact of the disease and its progression on the patient's physical disability. A patient will stand with the toes of his/her shoes on the starting line (identified by a taped mark on the floor) and timing will begin when any part of the patient's foot crosses the tape. Timing will end when any part of the patient's foot crosses the finish line (identified by a taped mark on the floor). Time will be recorded in seconds and rounded to the nearest tenth of a second using a stopwatch provided for this study.
Secondary Outcomes
- Change From Baseline in Walking Speed Near Minimum Plasma Concentration at Steady State (CminSS) of Placebo, Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW).(Baseline Visit 1 (double-blind study day 1) and approximately 12 hours post dose at Visit 3 (end of double-blind week 4))
- Change From Baseline in 12-item MS Walking Scale (MSWS-12) at Visit 3(Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4))
- Change From Baseline in MSWS-12 at Visit 2(Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period ))
- Change From Baseline in Six-Minute Walk Distance at Visit 2(Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period ))
- Change From Baseline in EuroQol Group 5 Dimensions (EQ-5D) Scores at Visit 3.(Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4))
- Change From Baseline in EQ-5D Visual Analogue Self-rating (VAS) Score at Visit 3.(Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4))