title: Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures.
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.
  
  
  METHODS
  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.
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA. gkrauss@jhmi.edu
authors.forename: G L
authors.initials: GL
authors.lastname: Krauss
authors.forename: J M
authors.initials: JM
authors.lastname: Serratosa
authors.forename: V
authors.initials: V
authors.lastname: Villanueva
authors.forename: M
authors.initials: M
authors.lastname: Endziniene
authors.forename: Z
authors.initials: Z
authors.lastname: Hong
authors.forename: J
authors.initials: J
authors.lastname: French
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: D
authors.initials: D
authors.lastname: Squillacote
authors.forename: H B
authors.initials: HB
authors.lastname: Edwards
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: A
authors.initials: A
authors.lastname: Laurenza
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects; D004828:Epilepsies, Partial / Q000188:drug therapy*; D017029:Epilepsy, Complex Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D009570:Nitriles; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel