Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures

Neurology. 2012 May 1;78(18):1408-15. doi: 10.1212/WNL.0b013e318254473a. Epub 2012 Apr 18.

Abstract

Objective: To evaluate the efficacy and safety of perampanel 2, 4, and 8 mg/day added to 1-3 concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures.

Methods: During this double-blind, placebo-controlled trial, patients with persisting seizures on 1-3 AEDs were randomized to perampanel 2, 4, and 8 mg/day or placebo following a 6-week baseline phase. Perampanel was titrated weekly by 2 mg/day and maintained at the dose achieved for 13 weeks. Primary endpoints were median percent change in seizure frequency and 50% responder rate. Analysis of covariance was performed on all treated patients with any seizure data (recorded in daily diaries) in the double-blind phase.

Results: A total of 706 patients were randomized and received trial medication; 623 completed the trial. Median percent change in seizure frequency-the primary efficacy endpoint-was -10.7%, -13.6%, -23.3%, and -30.8% for placebo, perampanel 2, 4, and 8 mg/day, respectively. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0026) and 8 mg/day (p < 0.0001). The corresponding 50% responder rates were 17.9%, 20.6%, 28.5%, and 34.9%. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0132) and 8 mg/day (p = 0.0003). An apparent dose response was suggested for dizziness, which was the most frequent treatment-emergent adverse event.

Conclusions: This trial demonstrated that adjunctive perampanel effectively reduced seizure frequency and possessed a favorable tolerability profile in patients ≥12 years with partial-onset seizures (with or without secondary generalization), with a minimum effective dose of 4 mg/day.

Classification of evidence: This study provides Class I evidence that 4 and 8 mg/day doses of adjunctive perampanel are effective and tolerated in reducing partial-onset seizures.

Trial registration: ClinicalTrials.gov NCT00700310.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Child
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Electroencephalography / drug effects
  • Epilepsies, Partial / drug therapy*
  • Epilepsy, Complex Partial / drug therapy*
  • Female
  • Humans
  • Intention to Treat Analysis
  • Male
  • Pyridones / adverse effects
  • Pyridones / therapeutic use*
  • Young Adult

Substances

  • Anticonvulsants
  • Pyridones
  • perampanel

Associated data

  • ClinicalTrials.gov/NCT00700310