Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

Mult Scler. 2015 Sep;21(10):1322-31. doi: 10.1177/1352458514563591. Epub 2015 Jan 12.


Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS).

Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT).

Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW.

Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders.

Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders.

Keywords: Clinical trial; Timed 25-Foot Walk; dalfampridine; efficacy; long-term effects; multiple sclerosis; safety; sustained release; tolerability; walking speed.

Publication types

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

MeSH terms

  • 4-Aminopyridine / administration & dosage
  • 4-Aminopyridine / therapeutic use*
  • Adult
  • Aged
  • Double-Blind Method
  • Europe
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Potassium Channel Blockers / therapeutic use*
  • Treatment Outcome
  • Walking / physiology*


  • Potassium Channel Blockers
  • 4-Aminopyridine