A phase 3 trial of extended release oral dalfampridine in multiple sclerosis.

Abstract

OBJECTIVE:

A previous phase 3 study showed significant improvement in walking ability in multiple sclerosis (MS) patients treated with oral, extended-release dalfampridine (4-aminopyridine) 10mg twice daily. The current study was designed to confirm efficacy and further define safety and pharmacodynamics.

METHODS:

This was a 39-center, double-blind trial in patients with definite MS of any course type. Participants were randomized to 9 weeks of treatment with dalfampridine (10mg twice daily; n = 120) or placebo (n = 119). Response was defined as consistent improvement on the Timed 25-Foot Walk, with percentage of timed walk responders (TWRs) in each treatment group as the primary outcome. The last on-treatment visit provided data from 8 to 12 hours postdose, to examine maintenance of effect.

RESULTS:

One patient from each group was excluded from the modified Intention to Treat population. The proportion of TWRs was higher in the dalfampridine group (51/119 or 42.9%) compared to the placebo group (11/118 or 9.3%, p < 0.0001). The average improvement in walking speed among dalfampridine-treated TWRs during the 8-week efficacy evaluation period was 24.7% from baseline (95% confidence interval, 21.0-28.4%); the mean improvement at the last on-treatment visit was 25.7%, showing maintenance of effect over the interdosing period. There were no new safety findings.

INTERPRETATION:

This interventional study provides class 1 evidence that dalfampridine extended-release tablets produce clinically meaningful improvement in walking ability in a subset of people with MS, with the effect maintained between doses.

• Authors: Andrew D Goodman, Theodore R Brown, Keith R Edwards, Lauren B Krupp, Randall T Schapiro, Ron Cohen, Lawrence N Marinucci, Andrew R Blight, MSF204 Investigators
• Journal: Annals of neurology (Ann Neurol) Vol. 68 Issue 4 Pg. 494-502 (Oct 2010) ISSN: 1531-8249 [Electronic] United States
• PMID: 20976768 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channel Blockers
• 4-Aminopyridine

Topics

• 4-Aminopyridine (blood, therapeutic use)
• Adult
• Aged
• Disability Evaluation
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Male
• Middle Aged
• Movement Disorders (drug therapy, etiology)
• Multiple Sclerosis (blood, complications, drug therapy)
• Potassium Channel Blockers (blood, therapeutic use)
• Walking (physiology)
• Young Adult