Fampridine-SR In Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study
Goodman AD, Cohen JA, Cross A, Vollmer T, Rizzo M, Cohen R, Marinucci L, Blight AR
Mult Scler 2007 Apr;13(3):357-68
University of Rochester, Department of Neurology, Rochester, NY 14642, USA
To determine the safety of sustained-release 4-AminoPyridine in subjects with Mutiple Sclerosis (MS) and to examine dose-related efficacy up to 40 mg twice daily.
Multicenter, randomized, double-blind, placebo-controlled, study. Following a 4-week baseline peroid, subjects were randomly assigned to receive Fampridine-SR (n=25, doses from 10 to 40 mg twice daily, increasing in 5 mg increments weekly) or placebo (n=11).
A battery of assessments was performed weekly, including the MS Functional Composite (MSFC), fatigue questionnaires, and lower extremity manual muscle testing.
The most common adverse events were Dizziness, Insomnia, Paresthesia, Asthenia, Nausea, Headache, and Tremor.
Five subjects were discontinued from Fampridine-SR because of adverse events at doses greater than 25 mg, and these included Convulsions in two subjects at doses of 30 and 35 mg twice daily.
Improvement were seen in lower extremity muscle strength (prospective analysis) and walking speed (post-hoc analysis) in the Fampridine-SR group compared to placebo (unadjusted p-values of 0.01 and 0.03, respectively).
There were no significant differences in other MSFC measure or fatigue scores.
Future studies should employ doses up to 20 mg twice daily with lower extremity strength and walking speed as potential outcome measures.
Effect Of 4-AminoPyridine On Gait In Ambulatory Spinal Cord Injuries: A Double-Blind, Placebo-Controlled, Crossover Trial
DeForge D, Nymark J, Lemaire E, Gardner S, Hunt M, Martel L, Curran D, Barbeau H
Spinal Cord 2004 Dec;42(12):674-85
University of Ottawa, Division of Physical Medicine and Rehabilitation, Ottawa, Ontario, Canada
Animal and human research have shown that the drug 4-AminoPyridine (4-AP) may improve Gait in Spinal Cord lesions by enhancing nerve transmission to affected muscles.
Prospective, randomized, double-blind, placebo-controlled, crossover trial.
To determine the efficacy of 4-AP in improving lower limb muscle strength and biomechanical Gait patterns of Chronic Spinal Cord Injuries (SCI).
The Rehabilitation Centre (Ottawa, Canada).
In all, 15 chronic, ambulatory SCI persons were randomized to an initial 2 weeks of 40 mg/day, oral medication of either placebo or immediate-release, 4-AP.
And, subsequently crossed over to the alternate medication for the following 2 weeks.
Evaluations were conducted at baseline (before starting 4-AP or placebo medication), 2 weeks, and 4 weeks.
Measures included Dynamometer Lower Limb Isometric Muscle Force and BioMechanical Gait Measures including Temporal-Spatial Parameters, ElectroMyographic Activation Patterns, Joint Kinematics and Kinetics.
Subjective impressions of the drug by the participants were obtained from an exit survey.
Despite some positive comments from subjects:
Statistical and clinical analyses showed no within-subject differences between placebo and 4-AP measures of lower limb muscle force and Objective Gait Analyses (ANOVA statistic P > 0.05).
Results demonstrated the importance of placebo-controlled trials and quantitative outcome measures for the evaluation of 4-AP aimed to enhance Gait for Chronic, Ambulatory SCI persons.
Energy expenditure measures and mood may relate more to subjective comments and is suggested for future investigations.
Dose Comparison Trial Of Sustained-Release Fampridine In Multiple Sclerosis
Goodman AD, Brown TR, Cohen JA, Krupp LB, Schapiro R, Schwid SR, Cohen R, Marinucci LN, Blight AR; For the Fampridine MS-F202 Study Group
Neurology 2008 Oct 7;71(15):1134-41
University of Rochester, Department of Neurology, NY; Evergreen Hospital Medical Center, Department of Neurology, Seattle, WA; Cleveland Clinic Foundation, Department of Neurology, OH; Stony Brook University Hospital, Department of Neurology, NY; Minneapolis Clinic of Neurology, MN; and Acorda Therapeutics, Inc., Hawthorne, NY
To examine the efficacy and safety of three different doses of sustained-release Fampridine in people with Multiple Sclerosis (MS).
This multicenter, randomized, double-blind, placebo-controlled, parallel-group study recruited 206 participants at 24 centers in the United States and Canada.
After a single-blind, 2-week placebo run-in, participants were randomly assigned to receive Fampridine (10, 15, or 20 mg twice daily) or placebo for 15 weeks.
The primary efficacy variable was percent change in walking speed based on the timed 25-foot walk.
Trends for increased walking speed were consistent across dose groups vs placebo, but not significant, on the prospective analysis.
An increase from baseline in lower extremity strength during the 12-week stable-dose period was seen in the groups receiving 10- and 15-mg doses, compared with placebo (p = 0.018 and 0.003).
There were no significant changes in other secondary assessments.
Post hoc analysis revealed subsets of participants in each dose group with walking speeds during the treatment period that were consistently faster than during the nontreatment period.
There were significantly more "consistent responders" in the drug-treated groups than in the placebo group (36.7% compared with 8.5%).
Consistent responders showed significantly greater improvement in self-assessed ambulation on the 12-Item MS Walking Scale than did nonresponders. Fampridine was generally well tolerated.
Severe and serious adverse events were more frequent at the highest dose.
This phase 2 study suggests that a subgroup of patients, when treated with Fampridine, experiences a clinically relevant improvement in walking ability:
Which is sustained for at least 14 weeks.