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

Primary Purpose

Spinal Cord Injury, Muscle Spasticity

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Fampridine-SR
Placebo
Sponsored by
Acorda Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injury focused on measuring spinal cord injury, muscle spasticity

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UAB School of Medicine, 190 Spain Rehab Center
  • Long Beach VA Medical Center
  • University of California, Davis
  • Santa Clara Valley Medical Center
  • Craig Hospital
  • Hospital for Special Care
  • Hines VA Hospital
  • Boston University Medical Center
  • University of Michigan
  • Rehabilitation Institute of Michigan
  • Minneapolis VA Hospital
  • University of Missouri
  • St. Louis University
  • University of Rochester/Strong Memorial Hospital
  • SUNY Upstate Clinical Trials Office
  • Helen Hayes Hospital
  • Charlotte Institute of Rehabilitation
  • Coastal AHEC
  • Ohio State University
  • Miami Valley Hospital- Rehabilitation Institute of Medicine
  • Thomas Jefferson University Hospital
  • VA North Texas Health Care System
  • Southwestern Medical Center at Dallas
  • INOVA Institute of Research and Education
  • Medical College of Virginia/VCU
  • University of Washington Medical Center, Dept. of Rehabilitation
  • Wood VA Medical Center
  • Health Sciences Centre
  • Chedoke-McMaster Hospital
  • St. Mary's of the Lake Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

fampridine-SR 50mg/day

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity
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.
Double-blind Change From Baseline in Mean Subject's Global Impression (SGI) Scores
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.

Secondary Outcome Measures

Double-blind Change From Baseline in Mean Spasm Frequency/Severity Scores
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.
Double-blind Change From Baseline in Mean Clinician's Global Impression (CGI) Scores
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.
Stable-dose Change From Baseline in Mean American Spinal Injury Association(ASIA) Total Motor Score
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.
Change From Baseline in Mean International Index of Erectile Function (IIEF) Score
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.
Change From Baseline in Mean Female Sexual Function Index (FSFI) Scores
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.
Adjusted Mean Change in Subject Bladder/Bowel Function Diary Scores
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.
Adjusted Mean Change in Subject Bowel Function Diary Scores
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.

Full Information

First Posted
August 24, 2012
Last Updated
July 27, 2017
Sponsor
Acorda Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT01683838
Brief Title
Safety and Efficacy of Oral Fampridine-Sustained Release (SR) for the Treatment of Spasticity Resulting From Spinal Cord Injury
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
June 2002 (undefined)
Primary Completion Date
November 2003 (Actual)
Study Completion Date
February 2004 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acorda Therapeutics

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injury, Muscle Spasticity
Keywords
spinal cord injury, muscle spasticity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
204 (Actual)

8. Arms, Groups, and Interventions

Arm Title
fampridine-SR 50mg/day
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Fampridine-SR
Intervention Description
25mg bid (twice daily)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Double-blind Change From Baseline in Ashworth Score Evaluating Spasticity
Description
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.
Time Frame
Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98
Title
Double-blind Change From Baseline in Mean Subject's Global Impression (SGI) Scores
Description
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.
Time Frame
Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98
Secondary Outcome Measure Information:
Title
Double-blind Change From Baseline in Mean Spasm Frequency/Severity Scores
Description
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.
Time Frame
Baseline (visits 2,3) average score days 7,14 and double-blind treatment period (visits 4-7) average score days 28-98
Title
Double-blind Change From Baseline in Mean Clinician's Global Impression (CGI) Scores
Description
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.
Time Frame
Baseline (visits 2,3) average of days 7-14 and double-blind treatment period (visits 4-7) average of days 28-98)
Title
Stable-dose Change From Baseline in Mean American Spinal Injury Association(ASIA) Total Motor Score
Description
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.
Time Frame
Baseline (visits 2,3) average score days 7,14 and stable-dose treatment period (visits 5-7) average score days 56-98
Title
Change From Baseline in Mean International Index of Erectile Function (IIEF) Score
Description
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.
Time Frame
Baseline (visit 1) average score obtained at day 1 and stable treatment period (visit 7) average score day 98
Title
Change From Baseline in Mean Female Sexual Function Index (FSFI) Scores
Description
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.
Time Frame
Baseline (visit 1) average score obtained at day 1 and stable treatment period (visits 4-7) average score days 28-98
Title
Adjusted Mean Change in Subject Bladder/Bowel Function Diary Scores
Description
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.
Time Frame
Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98
Title
Adjusted Mean Change in Subject Bowel Function Diary Scores
Description
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.
Time Frame
Baseline (visit 1) average score obtained at day 1 and double-blind treatment period (visits 4-7) average score days 28-98

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Blight, MD
Organizational Affiliation
Acorda Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
UAB School of Medicine, 190 Spain Rehab Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Long Beach VA Medical Center
City
Long Beach
State/Province
California
ZIP/Postal Code
90822
Country
United States
Facility Name
University of California, Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Santa Clara Valley Medical Center
City
San Jose
State/Province
California
ZIP/Postal Code
95128
Country
United States
Facility Name
Craig Hospital
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80110
Country
United States
Facility Name
Hospital for Special Care
City
New Britain
State/Province
Connecticut
ZIP/Postal Code
06503
Country
United States
Facility Name
Hines VA Hospital
City
Hines
State/Province
Illinois
ZIP/Postal Code
60141
Country
United States
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Rehabilitation Institute of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Minneapolis VA Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55417
Country
United States
Facility Name
University of Missouri
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
St. Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
University of Rochester/Strong Memorial Hospital
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
SUNY Upstate Clinical Trials Office
City
Syracuse
State/Province
New York
ZIP/Postal Code
13045
Country
United States
Facility Name
Helen Hayes Hospital
City
West Haverstraw
State/Province
New York
ZIP/Postal Code
13045
Country
United States
Facility Name
Charlotte Institute of Rehabilitation
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Coastal AHEC
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28402
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Miami Valley Hospital- Rehabilitation Institute of Medicine
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
VA North Texas Health Care System
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States
Facility Name
Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
INOVA Institute of Research and Education
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Medical College of Virginia/VCU
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Washington Medical Center, Dept. of Rehabilitation
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Wood VA Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53295
Country
United States
Facility Name
Health Sciences Centre
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1M4
Country
Canada
Facility Name
Chedoke-McMaster Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
St. Mary's of the Lake Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5A2
Country
Canada

12. IPD Sharing Statement

Links:
URL
http://www.acorda.com
Description
Related Info

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

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