Amifampridine Phosphate (Firdapse) Is Effective in a Confirmatory Phase 3 Clinical Trial in LEMS

Perry Shieh, Khema Sharma, Bruce Kohrman, Shin J. Oh

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Objective: To assess tolerability and efficacy of amifampridine phosphate versus placebo for symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS). Methods: This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in 26 adults with LEMS compared efficacy of amifampridine phosphate versus placebo over a 4-day period. The primary endpoints were quantitative myasthenia gravis score (QMG) and subject global impression, and the secondary endpoint was Clinical Global Impression-Improvement. The exploratory endpoints were 3TUG (timed up and go) test and QMG limb domain score. All participants had been receiving amifampridine phosphate (30-80 mg/d divided into 3 or 4 doses daily) in an expanded access protocol and had been titrated to the optimal dose and frequency for at least 1 week before randomization into the current study. After completion of assessments after 4 days of double-blind treatment, patients had the option to return to open-label amifampridine phosphate. The efficacy endpoints were mean changes from baseline in the various evaluation parameters. Results: Amifampridine phosphate (n = 13) demonstrated significant benefit in QMG and subject global impression compared with placebo (n = 13) at 4 days. Other measures of efficacy, including Clinical Global Impression-Improvement, 3TUG, and QMG limb domain score also improved. The most common "adverse events" in the placebo group were muscle weakness (n = 5) and fatigue (n = 4), as expected from withdrawal of amifampridine phosphate, whereas only back pain (n = 1), pain in extremity (n = 1), and headache (n = 1) were reported in amifampridine phosphate group. Conclusions: This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in adults with LEMS provided class I evidence of efficacy of amifampridine phosphate as symptomatic treatment in LEMS.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalJournal of clinical neuromuscular disease
Volume20
Issue number3
DOIs
StatePublished - Mar 1 2019

Keywords

  • 3,4 DAP
  • Firdapse
  • LEMS
  • Lambert-Eaton syndrome
  • amifampridine
  • clinical trials
  • diaminopyridine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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