Two phase 3, multicenter, randomized, placebo-controlled clinical trials of fampridine-SR for treatment of spasticity in chronic spinal cord injury

Spinal Cord. 2014 Jan;52(1):70-6. doi: 10.1038/sc.2013.137. Epub 2013 Nov 12.

Abstract

Study design: Two randomized, double-blind, placebo-controlled trials.

Objective: To evaluate the efficacy and safety of fampridine sustained-release tablets (fampridine-SR) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury (SCI).

Setting: United States and Canada.

Methods: Patients with incomplete chronic SCI were randomized to twice daily fampridine-SR 25 mg or placebo, with a 2-week single-blind placebo run-in, a 2-week titration, 12 weeks of stable dosing, 2 weeks of downward titration and 2 weeks of untreated follow-up. Co-primary end points were the change from baseline, averaged over the double-blind treatment period, for Ashworth score (bilateral knee flexors and extensors) and a 7-point Subject Global Impression of treatment (SGI; 1, terrible; 7, delighted). Secondary end points were: Penn Spasm Frequency Scale; the motor/sensory score from the International Standards for Neurological Classification of SCI; Clinician's Global Impression of Change of neurological status; and the International Index of Erectile Function (men) or the Female Sexual Function Index (women).

Results: The populations were 212 and 203 patients in the two studies, respectively. Changes from baseline in Ashworth score were -0.15 (placebo) and -0.19 (fampridine-SR) in the first study, and -0.16 (placebo) and -0.28 (fampridine-SR) in the second study. The between-treatment difference was not significant for either the Ashworth score or the SGI and, with few exceptions, neither were the secondary end points. Fampridine-SR was generally well tolerated; treatment-emergent adverse events (TEAEs) and serious TEAEs were reported with similar frequency between treatments.

Conclusion: Fampridine-SR was well tolerated. No significant differences were observed between treatment groups for the primary end points of Ashworth score and SGI.

Publication types

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

MeSH terms

  • 4-Aminopyridine / therapeutic use*
  • Adult
  • Canada
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Muscle Spasticity / drug therapy*
  • Muscle Spasticity / etiology
  • Potassium Channel Blockers / therapeutic use*
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / drug therapy*
  • Treatment Outcome
  • United States

Substances

  • Potassium Channel Blockers
  • 4-Aminopyridine