Study of Fampridine-ER Tablets in Patients With Multiple Sclerosis

NCT01328379 | Completed Phase 3 Results DMC

• 1 other identifier: DER-401
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 70

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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)

Study Arms (3)

Dalfampridine-ER 5mg

ACTIVE COMPARATOR

5mg, twice daily

Drug: Dalfampridine-ER 5mg

Dalfampridine-ER 10mg

ACTIVE COMPARATOR

10mg, twice daily

Drug: Dalfampridine-ER 10mg

Placebo

PLACEBO COMPARATOR

placebo, twice daily

Other: Placebo

Interventions

Dalfampridine-ER 5mg DRUG

5mg, twice daily

Also known as: Fampridine, Dalfampridine, Ampyra

Dalfampridine-ER 5mg

Dalfampridine-ER 10mg DRUG

10mg, twice daily

Also known as: Fampridine, Dalfampridine, Ampyra

Dalfampridine-ER 10mg

Placebo OTHER

placebo, twice daily

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Acorda Therapeutics: lead

Study Sites (70)

North Central Neurology Associates, PC

Cullman, Alabama, United States

Location

Phoenix Neurological Associates, Ltd

Phoenix, Arizona, United States

Location

Arizona Neurological Institute

Sun City, Arizona, United States

Location

Clinical Research Advantage Inc.

Tempe, Arizona, United States

Location

Sutter East Bay Physicians Medical Foundation

Berkeley, California, United States

Location

Neuro-Pain Medical Center, Inc.

Fresno, California, United States

Location

Loma Linda University Medical Center

Loma Linda, California, United States

Location

Collaborative NeuroScience Network, Inc.

Long Beach, California, United States

Location

University of California Davis Medical Center

Sacramento, California, United States

Location

Mount Sinai Rehabilitation Hospital

Hartford, Connecticut, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Location

Neurology Associates, PA

Maitland, Florida, United States

Location

University of Miami School of Medicine, Dept. of Neurology

Miami, Florida, United States

Location

Neurological Associates

Pompano Beach, Florida, United States

Location

Neurologique Foundation, Inc.

Ponte Vedra, Florida, United States

Location

Negroski, Sutherland and Hanes Neurology

Sarasota, Florida, United States

Location

Suncoast Neuroscience Associates, Inc.

St. Petersburg, Florida, United States

Location

Tallahassee Neurological Clinic, PA

Tallahassee, Florida, United States

Location

Axiom Clinical Research of Florida

Tampa, Florida, United States

Location

The Multiple Sclerosis Center of Vero Beach

Vero Beach, Florida, United States

Location

Sheperd Center, Inc.

Atlanta, Georgia, United States

Location

Northwestern University

Chicago, Illinois, United States

Location

Consultants in Neurology Ltd.

Northbrook, Illinois, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, United States

Location

Josephson Wallack Munshower Neurology, PC

Indianapolis, Indiana, United States

Location

Methodist Plaza Specialty

Des Moines, Iowa, United States

Location

Ruan Neurology Clinic and Research Center

Des Moines, Iowa, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, United States

Location

Associates in Neurology, PSC

Lexington, Kentucky, United States

Location

University of Maryland, Maryland Center for Multiple Sclerosis

Baltimore, Maryland, United States

Location

Lahey Clinic

Lexington, Massachusetts, United States

Location

Springfield Neurology Associates, LLC

Springfield, Massachusetts, United States

Location

Wayne State University

Detroit, Michigan, United States

Location

Advanced Neurology Specialists

Great Falls, Montana, United States

Location

Veterans Administration Sierra Neveda Health Care System

Reno, Nevada, United States

Location

Upstate Clinical Research, LLC

Albany, New York, United States

Location

NYU Langone Medical Center MS Comprehensive Care Center

New York, New York, United States

Location

Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates

Patchogue, New York, United States

Location

Island Neurological Associates, PC

Plainview, New York, United States

Location

University of Rochester Medical Center

Rochester, New York, United States

Location

PMG Research of Charlotte

Charlotte, North Carolina, United States

Location

The Neurological Institute, PA

Charlotte, North Carolina, United States

Location

PMG Research of Hickory, LLC

Hickory, North Carolina, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, United States

Location

PMG Research of Winston-Salem

Winston-Salem, North Carolina, United States

Location

Altru Health System Clinic

Grand Forks, North Dakota, United States

Location

Northern Ohio Neuroscience, LLC

Bellevue, Ohio, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Location

Neurological Research Institute

Columbus, Ohio, United States

Location

Ohio State University, Columbus

Columbus, Ohio, United States

Location

Neurology Specialists, Inc.

Dayton, Ohio, United States

Location

OMRF Multiple Sclerosis Center of Excellence

Oklahoma City, Oklahoma, United States

Location

Oregon Health and Science University

Portland, Oregon, United States

Location

Providence Multiple Sclerosis Center

Portland, Oregon, United States

Location

The Pennsylvania State University, Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, United States

Location

The Neurology Foundation, Inc.

Providence, Rhode Island, United States

Location

Wesley Neurology Clinic, PC

Cordova, Tennessee, United States

Location

Advanced Neurosciences Institute

Franklin, Tennessee, United States

Location

Sibyl E. Wray, MD, Neurology, PC

Knoxville, Tennessee, United States

Location

Texas Neurology, PA

Dallas, Texas, United States

Location

Kelsey-Seybold Clinic

Houston, Texas, United States

Location

Maxine Mesinger Multiple Sclerosis Clinic; Baylor College of Medicine

Houston, Texas, United States

Location

Fletcher Allen Health Care

Burlington, Vermont, United States

Location

Hampton Roads Neurology

Newport News, Virginia, United States

Location

Neurological Associates

Richmond, Virginia, United States

Location

Virginia Commonwealth University

Richmond, Virginia, United States

Location

Swedish Neuroscience Institute

Seattle, Washington, United States

Location

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States

Location

Related Publications (2)

• 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.

  PMID: 26565077 DERIVED

• 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.

  PMID: 25560174 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

4-Aminopyridine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Vice President - Clinical Development & Medical Affairs
• Organization: Acorda Therapeutics

hhenney@acorda.com

(914) 347- 4300

Study Officials

• Andrew R. Blight, PhD

  Acorda Therapeutics

  STUDY DIRECTOR

• 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

• Francois Bethoux, MD

  The Cleveland Clinic

  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

  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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2011
• First Posted: April 4, 2011
• Study Start: March 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: July 1, 2012
• Last Updated: September 5, 2013
• Results First Posted: August 13, 2013

Record last verified: 2013-09

Locations

US (70)