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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Spinal Cord Injury, Muscle Spasticity

Intervention / Treatment
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* Drug: Fampridine-SR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: fampridine-SR 50mg/day<br> | Drug: Fampridine-SR<br>* 25mg bid (twice daily)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord injury, muscle spasticity