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Study of Fampridine-ER Tablets in Patients With Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Acorda Therapeutics
ClinicalTrials.gov Identifier:
NCT01328379
First received: March 29, 2011
Last updated: September 3, 2013
Last verified: September 2013

March 29, 2011
September 3, 2013
March 2011
April 2012   (final data collection date for primary outcome measure)
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) ] [ Designated as safety issue: No ]

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.

To evaluate the efficacy of two doses of Dalfampridine-ER (5 and 10 mg) twice daily, using the Timed 25 Foot Walk (T25FW). [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Measure the change from baseline in walking speed (T25FW) at approxiimately 3-4 hours post dose at Visit 3 (i.e. near CmaxSS for dalfampridine-ER at the end of double blind week 4).
Complete list of historical versions of study NCT01328379 on ClinicalTrials.gov Archive Site
  • 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). [ Time Frame: Baseline Visit 1 (double-blind study day 1) and approximately 12 hours post dose at Visit 3 (end of double-blind week 4) ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4) ] [ Designated as safety issue: No ]

    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

  • Change From Baseline in MSWS-12 at Visit 2 [ Time Frame: Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period ) ] [ Designated as safety issue: No ]

    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

  • Change From Baseline in Six-Minute Walk Distance at Visit 2 [ Time Frame: Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period ) ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4) ] [ Designated as safety issue: No ]

    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. [ Time Frame: Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4) ] [ Designated as safety issue: No ]
    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.
  • To evaluate changes in patient mobility, walking capacity and general health status. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To evaluate the efficacy of these doses in the improvement of walking speed around the time of trough plasma concentration of dalfampridine, to examine maintenance of effect. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Measure change from baseline in walking speed (T25FW) at approximately 12 hours post dose at Visit 3.
  • To evaluate changes in walking capacity as measured by the Six-Minute Walk (6MW) Test in a subset of centers. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Measure change from baseline in Six-Minute Walk distance at Visit 2.
  • To evaluate changes in patient mobility as measured by a self-report questionnaire (12-Item Multiple Sclerosis Walking Scale or MSWS-12). [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Measure change from baseline in MSWS-12 at Visits 2 and 3, separately.
  • To evaluate changes in general health status as measured by the EQ-5D questionnaire. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

    Measure changes from baseline in five specific dimensional scores of EQ-5D at Visit 3.

    Measure changes from baseline in average scores across 5 specific dimension of EQ-5D at Visit 3.

  • To evaluate the incidence of urinary tract infections. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    At every visit, a urine sample (clean catch urine specimen) will be taken for microscopic urinalysis to detect laboratory evidence suggestive of urinary tract infection (UTI). If the patient has symptoms of a UTI, a urine culture must be performed in addition to the urinalysis for confirmation of the diagnosis. A urine culture should also be performed if the urinalysis is positive, even if the patient has no symptoms of UTI.
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Multiple Sclerosis
  • Drug: Dalfampridine-ER 5mg
    5mg, twice daily
    Other Name: Fampridine, Dalfampridine, Ampyra
  • Drug: Dalfampridine-ER 10mg
    10mg, twice daily
    Other Name: Fampridine, Dalfampridine, Ampyra
  • Other: Placebo
    placebo, twice daily
  • Active Comparator: Dalfampridine-ER 5mg
    5mg, twice daily
    Intervention: Drug: Dalfampridine-ER 5mg
  • Active Comparator: Dalfampridine-ER 10mg
    10mg, twice daily
    Intervention: Drug: Dalfampridine-ER 10mg
  • Placebo Comparator: Placebo
    placebo, twice daily
    Intervention: Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
430
July 2012
April 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01328379
DER-401
Yes
Acorda Therapeutics
Acorda Therapeutics
Not Provided
Study Director: Andrew R. Blight, PhD Acorda Therapeutics
Principal Investigator: Mark Agius, MD University of California, Davis
Principal Investigator: Angela Applebee, MD Fletcher Allen Health Care
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 Veterans Administration Medical Center
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
Acorda Therapeutics
September 2013

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