Study of Fampridine-ER Tablets in Patients With Multiple Sclerosis
- Conditions
- Multiple Sclerosis
- Interventions
- Drug: Dalfampridine-ER 10mgOther: PlaceboDrug: Dalfampridine-ER 5mg
- Registration Number
- NCT01328379
- Lead Sponsor
- Acorda Therapeutics
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 430
- 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Ampyra® or dalfampridine (fampridine or 4 aminopyridine; 4-AP) in any formulation (including compounded), must have withdrawn from the drug for at least one month prior to the Screening Visit.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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dalfampridine-ER 10mg Dalfampridine-ER 10mg 10mg, twice daily Placebo Placebo placebo, twice daily Dalfampridine-ER 5mg Dalfampridine-ER 5mg 5mg, twice daily
- Primary Outcome Measures
Name Time Method 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). 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 Outcome Measures
Name Time Method 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) 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.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) The MSWS-12 is a multi-item rating scale that asks patients to rate limitations of their mobility due to MS during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). The scale assesses a range of activities of daily life that rely on walking, such as climbing stairs, moving around the home and walking distances outdoors. The MSWS-12 also addresses the quality of walking, with questions on the smoothness, speed, distance, effort, and mental concentration involved in walking, as well as the need for assistive devices.
For each visit, the MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100.
MSWS-12 Score = 100 \* \[(Sum of Items 1-12) - 12\]/48Change From Baseline in MSWS-12 at Visit 2 Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period ) The MSWS-12 is a multi-item rating scale that asks patients to rate limitations of their mobility due to MS during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). The scale assesses a range of activities of daily life that rely on walking, such as climbing stairs, moving around the home and walking distances outdoors. The MSWS-12 also addresses the quality of walking, with questions on the smoothness, speed, distance, effort, and mental concentration involved in walking, as well as the need for assistive devices.
For each visit, the MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100.
MSWS-12 Score = 100 \* \[(Sum of Items 1-12) - 12\]/48Change From Baseline in Six-Minute Walk Distance at Visit 2 Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period ) The Six-Minute Walk, a test of endurance, measures the distance that a patient can walk in a period of 6 minutes. Six-minute walk distance will be reported in feet.
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) Patients completed a brief, generic health status questionnaire: The five specific dimensional scores value patients' health related to mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each question has 3 distinguishable choices that can be analyzed using a 3-point scale (i.e. 1 = no problem, 2=some problems and 3= extreme problems).
A response of 1 indicates that the patient has no problem with the dimension tested and a response of 3 indicates that the patient has extreme problems with the dimension tested. For each visit, the average score of 5 dimensions was calculated by averaging the scores of 5 dimensions. EQ-5D final score ranges from 1-3.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) The EQ-5D is a brief questionnaire that asks patients to rate general state of health. The VAS score rates the general state of health of a patient with 100 for the best imaginable health state and 0 for the worst imaginable health state.
Trial Locations
- Locations (69)
Texas Neurology, PA
🇺🇸Dallas, Texas, United States
Swedish Neuroscience Institute
🇺🇸Seattle, Washington, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Altru Health System Clinic
🇺🇸Grand Forks, North Dakota, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Mount Sinai Rehabilitation Hospital
🇺🇸Hartford, Connecticut, United States
Phoenix Neurological Associates, Ltd
🇺🇸Phoenix, Arizona, United States
Sibyl E. Wray, MD, Neurology, PC
🇺🇸Knoxville, Tennessee, United States
Advanced Neurology Specialists
🇺🇸Great Falls, Montana, United States
Fletcher Allen Health Care
🇺🇸Burlington, Vermont, United States
Arizona Neurological Institute
🇺🇸Sun City, Arizona, United States
Lahey Clinic
🇺🇸Lexington, Massachusetts, United States
Veterans Administration Sierra Neveda Health Care System
🇺🇸Reno, Nevada, United States
Wesley Neurology Clinic, PC
🇺🇸Cordova, Tennessee, United States
Providence Multiple Sclerosis Center
🇺🇸Portland, Oregon, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of Miami School of Medicine, Dept. of Neurology
🇺🇸Miami, Florida, United States
Ruan Neurology Clinic and Research Center
🇺🇸Des Moines, Iowa, United States
Clinical Research Advantage Inc.
🇺🇸Tempe, Arizona, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
The Neurological Institute, PA
🇺🇸Charlotte, North Carolina, United States
North Central Neurology Associates, PC
🇺🇸Cullman, Alabama, United States
Neuro-Pain Medical Center, Inc.
🇺🇸Fresno, California, United States
Collaborative NeuroScience Network, Inc.
🇺🇸Long Beach, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
Methodist Plaza Specialty
🇺🇸Des Moines, Iowa, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Neurology Associates, PA
🇺🇸Maitland, Florida, United States
Neurologique Foundation, Inc.
🇺🇸Ponte Vedra, Florida, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
OMRF Multiple Sclerosis Center of Excellence
🇺🇸Oklahoma City, Oklahoma, United States
PMG Research of Charlotte
🇺🇸Charlotte, North Carolina, United States
The Neurology Foundation, Inc.
🇺🇸Providence, Rhode Island, United States
Neurology Specialists, Inc.
🇺🇸Dayton, Ohio, United States
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Advanced Neurosciences Institute
🇺🇸Franklin, Tennessee, United States
PMG Research of Hickory, LLC
🇺🇸Hickory, North Carolina, United States
Sutter East Bay Physicians Medical Foundation
🇺🇸Berkeley, California, United States
Neurological Associates
🇺🇸Richmond, Virginia, United States
Suncoast Neuroscience Associates, Inc.
🇺🇸Saint Petersburg, Florida, United States
Sheperd Center, Inc.
🇺🇸Atlanta, Georgia, United States
Consultants in Neurology Ltd.
🇺🇸Northbrook, Illinois, United States
Negroski, Sutherland and Hanes Neurology
🇺🇸Sarasota, Florida, United States
Ohio State University, Columbus
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Temple University School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Tallahassee Neurological Clinic, PA
🇺🇸Tallahassee, Florida, United States
The Multiple Sclerosis Center of Vero Beach
🇺🇸Vero Beach, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Maryland, Maryland Center for Multiple Sclerosis
🇺🇸Baltimore, Maryland, United States
Josephson Wallack Munshower Neurology, PC
🇺🇸Indianapolis, Indiana, United States
Springfield Neurology Associates, LLC
🇺🇸Springfield, Massachusetts, United States
NYU Langone Medical Center MS Comprehensive Care Center
🇺🇸New York, New York, United States
Neurological Research Institute
🇺🇸Columbus, Ohio, United States
Northern Ohio Neuroscience, LLC
🇺🇸Bellevue, Ohio, United States
Kelsey-Seybold Clinic
🇺🇸Houston, Texas, United States
Maxine Mesinger Multiple Sclerosis Clinic; Baylor College of Medicine
🇺🇸Houston, Texas, United States
Hampton Roads Neurology
🇺🇸Newport News, Virginia, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
The Pennsylvania State University, Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Associates in Neurology, PSC
🇺🇸Lexington, Kentucky, United States
Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates
🇺🇸Patchogue, New York, United States
PMG Research of Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
Upstate Clinical Research, LLC
🇺🇸Albany, New York, United States
Island Neurological Associates, PC
🇺🇸Plainview, New York, United States
Raleigh Neurology Associates
🇺🇸Raleigh, North Carolina, United States