Study of Fampridine-ER Tablets in Patients With Multiple Sclerosis

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Dalfampridine-ER 5mg; Drug: Dalfampridine-ER 10mg; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 430
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Cullman, Alabama, United States
      • North Central Neurology Associates, PC
  • Arizona
    • Phoenix, Arizona, United States
      • Phoenix Neurological Associates, LTD
    • Sun City, Arizona, United States
      • Arizona Neurological Institute
    • Tempe, Arizona, United States
      • Clinical Research Advantage Inc.
  • California
    • Berkeley, California, United States
      • Sutter East Bay Physicians Medical Foundation
    • Fresno, California, United States
      • Neuro-Pain Medical Center, Inc.
    • Loma Linda, California, United States
      • Loma Linda University Medical Center
    • Long Beach, California, United States
      • Collaborative Neuroscience Network, Inc.
    • Sacramento, California, United States
      • University of California Davis Medical Center
  • Connecticut
    • Hartford, Connecticut, United States
      • Mount Sinai Rehabilitation Hospital
  • District of Columbia
    • Washington, District of Columbia, United States
      • Georgetown University Hospital
  • Florida
    • Maitland, Florida, United States
      • Neurology Associates, PA
    • Miami, Florida, United States
      • University of Miami School of Medicine, Dept. of Neurology
    • Pompano Beach, Florida, United States
      • Neurological Associates
    • Ponte Vedra, Florida, United States
      • Neurologique Foundation, Inc.
    • Saint Petersburg, Florida, United States
      • Suncoast Neuroscience Associates, Inc.
    • Sarasota, Florida, United States
      • Negroski, Sutherland and Hanes Neurology
    • Tallahassee, Florida, United States
      • Tallahassee Neurological Clinic, PA
    • Tampa, Florida, United States
      • Axiom Clinical Research of Florida
    • Vero Beach, Florida, United States
      • The Multiple Sclerosis Center of Vero Beach
  • Georgia
    • Atlanta, Georgia, United States
      • Sheperd Center, Inc.
  • Illinois
    • Chicago, Illinois, United States
      • Northwestern University
    • Northbrook, Illinois, United States
      • Consultants in Neurology Ltd.
  • Indiana
    • Indianapolis, Indiana, United States
      • Indiana University School of Medicine
    • Indianapolis, Indiana, United States
      • Josephson Wallack Munshower Neurology, PC
  • Iowa
    • Des Moines, Iowa, United States
      • Methodist Plaza Specialty
    • Des Moines, Iowa, United States
      • Ruan Neurology Clinic and Research Center
  • Kansas
    • Kansas City, Kansas, United States
      • The University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States
      • Associates in Neurology, PSC
  • Maryland
    • Baltimore, Maryland, United States
      • University of Maryland, Maryland Center for Multiple Sclerosis
  • Massachusetts
    • Lexington, Massachusetts, United States
      • Lahey Clinic
    • Springfield, Massachusetts, United States
      • Springfield Neurology Associates, LLC
  • Michigan
    • Detroit, Michigan, United States
      • Wayne State University
  • Montana
    • Great Falls, Montana, United States
      • Advanced Neurology Specialists
  • Nevada
    • Reno, Nevada, United States
      • Veterans Administration Sierra Neveda Health Care System
  • New York
    • Albany, New York, United States
      • Upstate Clinical Research, LLC
    • New York, New York, United States
      • NYU Langone Medical Center MS Comprehensive Care Center
    • Patchogue, New York, United States
      • Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates
    • Plainview, New York, United States
      • Island Neurological Associates, PC
    • Rochester, New York, United States
      • University of Rochester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States
      • PMG Research of Charlotte
    • Charlotte, North Carolina, United States
      • The Neurological Institute, PA
    • Hickory, North Carolina, United States
      • PMG Research of Hickory, LLC
    • Raleigh, North Carolina, United States
      • Raleigh Neurology Associates
    • Winston-Salem, North Carolina, United States
      • PMG Research of Winston-Salem
  • North Dakota
    • Grand Forks, North Dakota, United States
      • Altru Health System Clinic
  • Ohio
    • Bellevue, Ohio, United States
      • Northern Ohio Neuroscience, LLC
    • Cleveland, Ohio, United States
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States
      • Neurological Research Institute
    • Columbus, Ohio, United States
      • Ohio State University, Columbus
    • Dayton, Ohio, United States
      • Neurology Specialists, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • OMRF Multiple Sclerosis Center of Excellence
  • Oregon
    • Portland, Oregon, United States
      • Oregon Health and Science University
    • Portland, Oregon, United States
      • Providence Multiple Sclerosis Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States
      • The Pennsylvania State University, Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Temple University School of Medicine
  • Rhode Island
    • Providence, Rhode Island, United States
      • The Neurology Foundation, Inc.
  • Tennessee
    • Cordova, Tennessee, United States
      • Wesley Neurology Clinic, PC
    • Franklin, Tennessee, United States
      • Advanced Neurosciences Institute
    • Knoxville, Tennessee, United States
      • Sibyl E. Wray, MD, Neurology, PC
  • Texas
    • Dallas, Texas, United States
      • Texas Neurology, PA
    • Houston, Texas, United States
      • Kelsey-Seybold Clinic
    • Houston, Texas, United States
      • Maxine Mesinger Multiple Sclerosis Clinic; Baylor College of Medicine
  • Vermont
    • Burlington, Vermont, United States
      • Fletcher Allen Health Care
  • Virginia
    • Newport News, Virginia, United States
      • Hampton Roads Neurology
    • Richmond, Virginia, United States
      • Neurological Associates
    • Richmond, Virginia, United States
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States
      • Swedish Neuroscience Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Aurora Saint Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dalfampridine-ER 5mg; 5mg, twice daily	Drug: Dalfampridine-ER 5mg; 5mg, twice daily; Other Names: Fampridine, Dalfampridine, Ampyra
Active Comparator: Dalfampridine-ER 10mg; 10mg, twice daily	Drug: Dalfampridine-ER 10mg; 10mg, twice daily; Other Names: Fampridine, Dalfampridine, Ampyra
Placebo Comparator: Placebo; placebo, twice daily	Other: Placebo; placebo, twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	Baseline Visit 1 (double-blind study day 1) and approximately 3-4 hours post dose at Visit 3 (end of double-blind week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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	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]/48	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	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]/48	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	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.	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.	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.	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.	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.	Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)

Collaborators and Investigators

• Sponsor: Acorda Therapeutics
• Investigators: Study Director: Andrew R. Blight, PhD, Acorda Therapeutics; Principal Investigator: Mark Agius, MD, University of California, Davis; Principal Investigator: Angela Applebee, MD, University of Vermont Medical Center; Principal Investigator: S. A Azizi, MD, PhD, Temple University Hospital; Principal Investigator: Christopher Bever, Jr., MD, University of Maryland, Maryland Center for Multiple Sclerosis; Principal Investigator: Eric Borresen, MD, Metrolina Medical Research; Principal Investigator: Aaron Boster, MD, Ohio State University, Columbus; Principal Investigator: Ann Camac, MD, Lahey Clinic; Principal Investigator: Mark Cascione, MD, Axiom Clinical Research of Florida; Principal Investigator: Jane Chan, MD, US Department of Veterans Affairs; Principal Investigator: Warren Chumley, MD, Associates in Neurology, PSC; Principal Investigator: Joanna Cooper, MD, Alta Bates Summit Medical Center; Principal Investigator: Joy Derwenskus, DO, Northwestern University; Principal Investigator: Adam DiDio, MD, Suncoast Neuroscience Associates, Inc.; Principal Investigator: Dennis Dietrich, MD, Advanced Neurology Specialists; Principal Investigator: Geoffery Eubank, MD, Neurological Research Institute; Principal Investigator: Steven Freedman, MD, Raleigh Neurology Associates; Principal Investigator: Daniel Giang, MD, Loma Linda University Medical Center; Principal Investigator: Lawrence Goldstick, MD, Neurology Specialists, Inc.; Principal Investigator: Andrew Goodman, MD, University of Rochester; Principal Investigator: Mark Gudesblatt, MD, Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.; Principal Investigator: Barry Hendin, MD, Phoenix Neurological Associates, LTD; Principal Investigator: Craig Herrman, MD, Josephson Wallack Munshower Neurology, PC; Principal Investigator: William Honeycutt, MD, Neurology Associates, PA; Principal Investigator: Bruce Hughes, MD, Ruan Neurology Clinical Research Center; Principal Investigator: Samuel Hunter, MD, PhD, Advanced Neurosciences Institute; Principal Investigator: George Hutton, MD, Maxine Mesinger Multiple Sclerosis Clinic; Baylor College of Medicine; Principal Investigator: Dina Jacobs, MD, University of Pennsylvania; Principal Investigator: Todd Janus, MD, PhD, Iowa Health Des Moines; Principal Investigator: Omar Khan, MD, Wayne State University; Principal Investigator: Bhupendra Khatri, MD, Aurora Saint Luke's Medical Center; Principal Investigator: Kiren Kresa-Reahl, MD, Charleston Area Medical Center Health Education and Research Institute, Inc.; Principal Investigator: Christopher LaGanke, MD, North Central Neurology Associates, PC; Principal Investigator: Sharon Lynch, MD, The University of Kansas Medical Center; Principal Investigator: Michele Mass, MD, Oregon Health and Science University; Principal Investigator: David Mattson, MD, PhD, Indiana University; Principal Investigator: Angeli Mayadev, MD, Swedish Neuroscience Institute; Principal Investigator: Donald Negroski, MD, Negroski, Stein, Sutherland and Hanes Neurology; Principal Investigator: Stephen Newman, MD, Island Neurological Associates, PC; Principal Investigator: Gabriel Pardo, MD, Mercy Multiple Sclerosis Center of Oklahoma Mercy Neuroscience Institute; Principal Investigator: C. Fish Greenfield, MD, Texas Neurology, PA; Principal Investigator: Rekha Pillai, MD, Neurology Clinic, PC; Principal Investigator: T. Hemanth Rao, MD, The Neurological Institute, PA; Principal Investigator: Syed Rizvi, MD, Rhode Island Hospital; Principal Investigator: Matthew Roller, MD, Altru Health System Research Center; Principal Investigator: Michael Rossen, MD, PhD, Springfield Neurology Associates, LLC; Principal Investigator: Alan Schulman, MD, Neurological Associates; Principal Investigator: James S Shafer, MD, The Multiple Sclerosis Center of Vero Beach; Principal Investigator: Jatin Shah, MD, Arizona Neurological Institute; Principal Investigator: William Sheremata, MD, University of Miami School of Medicine, Dept. of Neurology; Principal Investigator: Brian Steingo, MD, Neurological Associates; Principal Investigator: James Storey, Jr, MD, Upstate Clinical Research, LLC; Principal Investigator: Ben Thrower, MD, Shepherd Center, Inc.; Principal Investigator: Carlo Tornatore, MD, Georgetown University Hospital; Principal Investigator: K A Lloyd, MD, Hampton Roads Neurology; Principal Investigator: Anthony Turel, Jr, MD, The Pennsylvania State University, Milton S. Hershey Medical Center; Principal Investigator: Sibyl E Wray, MD, Sibyl E. Wray, MD, Neurology, PC; Principal Investigator: Daniel Wynn, MD, Consultants in Neurology Ltd.; Principal Investigator: Robert Yapundich, MD, Unifour Medical Research, LLC

Publications and helpful links

General Publications

• Applebee A, Goodman AD, Mayadev AS, Bethoux F, Goldman MD, Klingler M, Blight AR, Carrazana EJ. Effects of Dalfampridine Extended-release Tablets on 6-minute Walk Distance in Patients With Multiple Sclerosis: A Post Hoc Analysis of a Double-blind, Placebo-controlled Trial. Clin Ther. 2015 Dec 1;37(12):2780-7. doi: 10.1016/j.clinthera.2015.10.014. Epub 2015 Nov 10.
• Kantor D, Chancellor MB, Snell CW, Henney HR 3rd, Rabinowicz AL. Assessment of confirmed urinary tract infection in patients treated with dalfampridine for multiple sclerosis. Postgrad Med. 2015 Mar;127(2):218-22. doi: 10.1080/00325481.2015.1000229. Epub 2015 Jan 6.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: March 29, 2011
• First Submitted That Met QC Criteria: April 1, 2011
• First Posted (Estimate): April 4, 2011

Study Record Updates

• Last Update Posted (Estimate): September 5, 2013
• Last Update Submitted That Met QC Criteria: September 3, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: DER-401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No