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

Ann Neurol. 2010 Oct;68(4):494-502. doi: 10.1002/ana.22240.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Potassium Channel Blockers
  • 4-Aminopyridine