title: 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.
abstract: 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).
  
  
  OBJECTIVE
  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.
authors.affiliation: University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Goodman
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Francois
authors.initials: F
authors.lastname: Bethoux
authors.affiliation: Evergreen Neuroscience Institute and Medical Center, Kirkland, WA, USA.
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Brown
authors.affiliation: The Schapiro Multiple Sclerosis Advisory Group, Eagle, CO, USA.
authors.forename: Randall T
authors.initials: RT
authors.lastname: Schapiro
authors.affiliation: Acorda Therapeutics, Ardsley, NY, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Acorda Therapeutics, Ardsley, NY, USA.
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Marinucci
authors.affiliation: Acorda Therapeutics, Ardsley, NY, USA.
authors.forename: Herbert R
authors.initials: HR
authors.lastname: Henney
authors.affiliation: Acorda Therapeutics, Ardsley, NY, USA ablight@acorda.com.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Blight
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology*
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine
keywords: Clinical trial; Timed 25-Foot Walk; dalfampridine; efficacy; long-term effects; multiple sclerosis; safety; sustained release; tolerability; walking speed