Multiple Sclerosis
Conditions
Keywords
Walking Ability, Muscle strength, Spasticity
Brief summary
Multiple Sclerosis (MS) is a disorder of the body's immune system that affects the Central Nervous System (CNS). Normally, nerve fibers carry electrical impulses through the spinal cord, providing communication between the brain and the arms and legs. In people with MS, the fatty sheath that surrounds and insulates the nerve fibers (called myelin) deteriorates, causing nerve impulses to be slowed or stopped. As a result patients with MS may experience periods of muscle weakness and other symptoms such as numbness, loss of vision, loss of coordination, paralysis, spasticity, mental and physical fatigue and a decrease in the ability to think and/or remember. These periods of illness may come (exacerbations) and go (remissions). Fampridine-SR (Sustained Release, SR) is an experimental drug that increases the ability of the nerve to conduct electrical impulses. This study will evaluate the effects of Fampridine-SR on the walking ability of subjects with MS, as well as to examine the effects on muscle strength and spasticity. The study will also examine the possible risks of taking Fampridine-SR.
Interventions
DRUGPlacebo
Placebo for 15 weeks
DRUG10 milligram (mg) fampridine-SR (4-aminopyridine, 4-AP)
2 week up titration (10 mg) 12 weeks stable dose (10 mg) 1 week down titration (10 mg)
DRUG15 mg fampridine-SR (4-aminopyridine, 4-AP)
10 mg twice daily for 1 week 15 mg twice daily for 14 weeks 2 week up titration (10 mg x 1 week, 15 mg x 1 week) 12 weeks stable dose (15 mg) 1 week down titration (10 mg)
DRUG20 mg fampridine-SR (4-aminopyridine, 4-AP)
2 week up titration (10 mg x 1 week, 15 mg x 1 week) 12 weeks stable dose (20 mg) 1 week down titration (15 mg x 3 days, 10 mg x 4 days)
Sponsors
Acorda Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Have a confirmed diagnosis of Multiple Sclerosis * Are able to walk with or without an assisted device
Exclusion criteria
* Pregnancy, breastfeeding or females of childbearing potential not using adequate birth control * Participating in other investigational drug trials * A medical history or clinical findings that preclude entry into the study * A medication history that precludes entry into the study * Previously treated with 4-aminopyridine (4-AP)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Percent Change From Baseline in Average Walking Speed on Timed 25-Foot Walk Test | Baseline (placebo run-in period); 12-week stable dose period | The primary efficacy variable was the percent change from baseline in average walking speed measured using the Timed 25-Foot Walk Test during the 12-week stable dose period (the average of Study Days 56, 84, and 112), relative to the mean at baseline (placebo run-in period, the average of Study Days 7 and 14). |
Countries
Canada, United States
Participant flow
Recruitment details
Patients with clinically definite MS were recruited at clinics within the US and Canada
Pre-assignment details
2-week placebo run-in
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo control | 47 |
| 10 mg Fampridine Twice a Day (b.i.d.) fampridine, oral, 10 mg administered twice daily | 52 |
| 15 mg Fampridine b.i.d. fampridine, oral, 15 mg administered twice daily | 50 |
| 20 mg Fampridine b.i.d. fampridine, oral, 20 mg administered twice daily | 57 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 5 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Overall Study | Non-Compliance | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | 10 mg Fampridine Twice a Day (b.i.d.) | 15 mg Fampridine b.i.d. | 20 mg Fampridine b.i.d. | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 50 Participants | 49 Participants | 55 Participants | 199 Participants |
| Age Continuous | 49.0 years STANDARD_DEVIATION 8.99 | 49.8 years STANDARD_DEVIATION 8.34 | 47.7 years STANDARD_DEVIATION 8.93 | 52.2 years STANDARD_DEVIATION 8.33 | 49.8 years STANDARD_DEVIATION 8.73 |
| Region of Enrollment Canada | 5 participants | 5 participants | 5 participants | 6 participants | 21 participants |
| Region of Enrollment United States | 42 participants | 47 participants | 45 participants | 51 participants | 185 participants |
| Sex: Female, Male Female | 27 Participants | 36 Participants | 34 Participants | 34 Participants | 131 Participants |
| Sex: Female, Male Male | 20 Participants | 16 Participants | 16 Participants | 23 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 38 / 47 | 45 / 52 | 47 / 50 | 52 / 57 |
| serious Total, serious adverse events | 2 / 47 | 0 / 52 | 4 / 50 | 7 / 57 |
Outcome results
Primary
Median Percent Change From Baseline in Average Walking Speed on Timed 25-Foot Walk Test
The primary efficacy variable was the percent change from baseline in average walking speed measured using the Timed 25-Foot Walk Test during the 12-week stable dose period (the average of Study Days 56, 84, and 112), relative to the mean at baseline (placebo run-in period, the average of Study Days 7 and 14).
Time frame: Baseline (placebo run-in period); 12-week stable dose period
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Median Percent Change From Baseline in Average Walking Speed on Timed 25-Foot Walk Test | 1.2 percent change | Full Range 18.9 |
| 10 mg Fampridine Twice a Day (b.i.d.) | Median Percent Change From Baseline in Average Walking Speed on Timed 25-Foot Walk Test | 7.5 percent change | Full Range 22.1 |
| 15 mg Fampridine b.i.d. | Median Percent Change From Baseline in Average Walking Speed on Timed 25-Foot Walk Test | 9.7 percent change | Full Range 23.7 |
| 20 mg Fampridine b.i.d. | Median Percent Change From Baseline in Average Walking Speed on Timed 25-Foot Walk Test | 6.9 percent change | Full Range 18.5 |