Study of Fampridine-ER Tablets in Patients With Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01328379
• Other study ID #: DER-401
• Status: Completed
• Phase: Phase 3
• First received: March 29, 2011
• Last updated: September 3, 2013
• Start date: March 2011
• Est. completion date: July 2012

Study information

• Verified date: September 2013
• Source: Acorda Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 430
• Est. completion date: July 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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Ampyra® or dalfampridine (fampridine or 4 aminopyridine; 4-AP) in any formulation (including compounded), must have withdrawn from the drug for at least one month prior to the Screening Visit.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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Dalfampridine-ER 5mg
5mg, twice daily
• Dalfampridine-ER 10mg
10mg, twice daily

Other:
• Placebo
placebo, twice daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Acorda Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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 )	No
Secondary	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 )	No
Secondary	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)	No
Secondary	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)	No