Safety and Efficacy of Oral Fampridine-Sustained Release (SR) for the Treatment of Spasticity Resulting From Spinal Cord Injury

July 27, 2017 updated by: Acorda Therapeutics

Double-Blind, Placebo-Controlled, 12-Week Parallel Group Study to Evaluate Safety and Efficacy of Oral Fampridine-SR in Subjects With Moderate to Severe Spasticity Resulting From Chronic, Incomplete Spinal Cord Injury

Normally, nerve fibers carry electrical impulses through the spinal cord, providing communication between the brain and the arms and legs. In people with spinal cord injury, some fibers may be destroyed at the site of injury, while others remain connected but do not work correctly to carry electrical impulses. As a result, subjects with an incomplete spinal cord injury may have spasticity which is muscle spasms or muscle stiffness that makes movement difficult. Fampridine-SR is an experimental drug that increases the ability of the nerve to conduct electrical impulses. This study will examine the effects of Fampridine-SR on moderate to severe lower-limb spasticity, as well as the effects on bodily functions such as bladder control, bowel function and sexual function. The study will also examine the possible risks of taking Fampridine-SR.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

204

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1M4
        • Health Sciences Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • Chedoke-McMaster Hospital
      • Kingston, Ontario, Canada, K7L 5A2
        • St. Mary's of the Lake Hospital
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • UAB School of Medicine, 190 Spain Rehab Center
    • California
      • Long Beach, California, United States, 90822
        • Long Beach VA Medical Center
      • Sacramento, California, United States, 95817
        • University of California, Davis
      • San Jose, California, United States, 95128
        • Santa Clara Valley Medical Center
    • Colorado
      • Englewood, Colorado, United States, 80110
        • Craig Hospital
    • Connecticut
      • New Britain, Connecticut, United States, 06503
        • Hospital for Special Care
    • Illinois
      • Hines, Illinois, United States, 60141
        • Hines VA Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Detroit, Michigan, United States, 48201
        • Rehabilitation Institute of Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Minneapolis VA Hospital
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri
      • Saint Louis, Missouri, United States, 63104
        • St. Louis University
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester/Strong Memorial Hospital
      • Syracuse, New York, United States, 13045
        • SUNY Upstate Clinical Trials Office
      • West Haverstraw, New York, United States, 13045
        • Helen Hayes Hospital
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Charlotte Institute of Rehabilitation
      • Wilmington, North Carolina, United States, 28402
        • Coastal AHEC
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospital- Rehabilitation Institute of Medicine
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
    • Texas
      • Dallas, Texas, United States, 75216
        • VA North Texas Health Care System
      • Dallas, Texas, United States, 75390
        • Southwestern Medical Center at Dallas
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • INOVA Institute of Research and Education
      • Richmond, Virginia, United States, 23298
        • Medical College of Virginia/VCU
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center, Dept. of Rehabilitation
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53295
        • Wood VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Incomplete traumatic Spinal Cord Injury (at least 18 months prior and stable for 6 months)
  • Moderate to severe lower-limb spasticity
  • Able to give informed consent and willing to comply with protocol

Exclusion Criteria:

  • Pregnancy
  • History of seizures
  • Existing or history of frequent Urinary Tract Infections
  • History of drug or alcohol abuse
  • Allergy to pyridine-containing substances
  • Received a botox injection 4 months prior to study
  • Received an investigational drug within 30 days
  • Previously treated with 4-aminopyridine (4-AP)
  • Not on stable medication dosing in 3 weeks prior to study
  • Abnormal ECG or laboratory value at screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo
Active Comparator: fampridine-SR 50mg/day
25mg bid (twice daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity
Time Frame: Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98

The Ashworth evaluates the functioning of two lower extremity muscle groups, the hamstring and quadriceps muscles, while in the supine position. The test measures extension of the right and left hamstring muscle and flexion of the right and left quadriceps muscle using the following 5-point grading scale:

1=no increased tone; 2=slight increase in tone, giving a "catch" when the affected part is moved in flexion or extension; 3=more marked increase in tone, but affected part is easily flexed; 4=considerable increase in tone, passive movement is difficult; 5=affected part is rigid in flexion and extension.

The Ashworth Score was determined by adding all individual scores for each muscle group and dividing by four. Higher Ashworth Scores indicated greater spasticity.

Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98
Double-blind Change From Baseline in Mean Subject's Global Impression (SGI) Scores
Time Frame: Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98

The SGI is a 7-unit ordinal scale used by the subject to evaluate the effects of study medication on his/her quality of life during the preceding week, with higher scores denoting greater satisfaction. A positive change score in SGI signifies improved outcome.

The questionnaire consisted of one question (How do you feel about the effects of the investigational drug over the past 7 days?). The answer was based on a numerical rating scale where 1=terrible; 2=unhappy; 3=mostly dissatisfied; 4=neutral/mixed; 5=mostly satisfied; 6=pleased; 7=delighted.

Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Double-blind Change From Baseline in Mean Spasm Frequency/Severity Scores
Time Frame: Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98

The Spasm Frequency score is the average rating by the clinician of the left and right arm(s) and leg(s), each evaluated on a 4-point scale (from 0=no spasms to 4=spontaneous spasms occurring more than ten times per hour), with higher scores denoting a greater degree of muscle spasms.

The Spasm Severity score is the average rating of the left and right arm(s) and leg(s), each evaluated on a three-point scale (mild, moderate, or severe) as rated by the clinician on the basis of patient self-report.

On both, a negative change in score signifies improvement in muscle spasms. The average Spasm Frequency/Spasm Severity Score was calculated as the average of the left and right non-missing scores.

Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98
Double-blind Change From Baseline in Mean Clinician's Global Impression (CGI) Scores
Time Frame: Baseline (visits 2,3) average of days 7-14 and double-blind treatment period (visits 4-7) average of days 28-98)
The supervising clinician rated the patient's neurological condition following treatment as compared to the screening visit on a seven-point scale (from 1=very much improved to 7=very much worse). The assessment was based on the clinician's overall impression of the patient's neurological status (specifically bowel, bladder, and sexual function; spasticity; and other neurological functions) and general state of health related to his or her participation in the study. Negative change scores indicated a change for the better.
Baseline (visits 2,3) average of days 7-14 and double-blind treatment period (visits 4-7) average of days 28-98)
Stable-dose Change From Baseline in Mean American Spinal Injury Association(ASIA) Total Motor Score
Time Frame: Baseline (visits 2,3) average score days 7,14 and stable-dose treatment period (visits 5-7) average score days 56-98
Ten key muscle groups for the right and left sides were rated on a 0 (absent) to 5 (normal) scale, with a possible total score of 100. Higher positive change scores indicate improved motor function.
Baseline (visits 2,3) average score days 7,14 and stable-dose treatment period (visits 5-7) average score days 56-98
Change From Baseline in Mean International Index of Erectile Function (IIEF) Score
Time Frame: Baseline (visit 1) average score obtained at day 1 and stable treatment period (visit 7) average score day 98

Male patients were asked to complete the IIEF questionnaire on sexual function. The IIEF is a brief, reliable, and valid self-administered questionnaire of 15 questions (items) that were categorized into five domains: Erectile Function (EF) scores: 0-6 Severe dysfunction, 7-12 Moderate dysfunction, 13-18 Mild to moderate dysfunction, 19-24 Mild dysfunction, 25-30 No dysfunction. Orgasmic Function (OF) score range: 0-2 Severe dysfunction to 9-10 No dysfunction, Sexual Desire (SD) score range: 0-2 Severe dysfunction to 9-10 No dysfunction, Intercourse Satisfaction (IS) score range: 0-3 Severe dysfunction to 13-15 No dysfunction, and Overall Satisfaction (OS) score range: 0-2 Severe dysfunction to 9-10 No dysfunction.

Domain scores were derived by summing the individual items within a given domain. Final scale ranges from 0 (negative) to 5 (positive). A positive change in IIEF domain scores signifies improvement.

Baseline (visit 1) average score obtained at day 1 and stable treatment period (visit 7) average score day 98
Change From Baseline in Mean Female Sexual Function Index (FSFI) Scores
Time Frame: Baseline (visit 1) average score obtained at day 1 and stable treatment period (visits 4-7) average score days 28-98

The FSFI is a brief, reliable, and valid self-administered questionnaire of 19 questions (items). It contains six domains: Desire (2 items score range: 1 Very low or none at all to 5 Very high), Arousal (4 items score range: 0 No sexual activity to 5 Almost always or always), Lubrication (4 items score range: 0 No sexual activity to 5 Almost always or always), Orgasm (3 items score range: 0 No sexual activity to 5 Almost always or always), Satisfaction (3 items score range: 0 No sexual activity to 5 Very satisfied) and Pain (3 items score range: 0 Did not attempt intercourse to 5 Almost never or never).

A positive change signifies improvement.

Baseline (visit 1) average score obtained at day 1 and stable treatment period (visits 4-7) average score days 28-98
Adjusted Mean Change in Subject Bladder/Bowel Function Diary Scores
Time Frame: Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98

Bowel/bladder questions pertaining to the average number of times per day the patient experienced accidental urination/leakage and the average number of bowel movements per day were asked of all patients daily.

A negative change in patient bladder/bowel function diary score signifies improvement.

Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98
Adjusted Mean Change in Subject Bowel Function Diary Scores
Time Frame: Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98

Bowel questions pertaining to the average number of minutes per day spent on bowel routine were asked of all patients daily.

A negative change in patient bowel function diary score signifies improvement.

Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Andrew Blight, MD, Acorda Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2002

Primary Completion (Actual)

November 1, 2003

Study Completion (Actual)

February 1, 2004

Study Registration Dates

First Submitted

August 24, 2012

First Submitted That Met QC Criteria

September 10, 2012

First Posted (Estimate)

September 12, 2012

Study Record Updates

Last Update Posted (Actual)

August 25, 2017

Last Update Submitted That Met QC Criteria

July 27, 2017

Last Verified

January 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Muscle Spasticity

Clinical Trials on Placebo

3
Subscribe