title: [Perampanel in treatment of refractory partial epilepsy in adolescents and adults: results of international multicenter randomized, double-blind, placebo-controlled phase III studies].
abstract: BACKGROUND
  Despite availability of many AEDs, failure rate of first AED used in children with newly diagnosed epilepsy remains as high as 20-40%. Although likelihood of seizure freedom declines with successive AEDs, almost 1 in 5 patients become seizure free with the addition of an alternative AED after failure of 2-5 agents. New AED - perampanel (PER) was developed as a selective, non-competitive AMPA receptor antagonist to target post-synaptic glutamate transmission.
  
  
  METHODS
  Efficacy and tolerability of PER in adolescents and adults with refractory partial seizures secondarily generalized and without generalization was assessed in international (global) randomized placebo-controlled prospective phase III trials with prolonged open follow-up phase. 1478 patients aged older than 12 years were included. All of them were unsuccessfully pretreated with 1-3 AEDs. Patients were randomized either to placebo or to 2, 4, 8, 12 mg of PER daily respectively. After completing the double blind phase they were transferred to open extension phase with titration of daily dose of PER up to 12 mg.
  
  
  RESULTS
  PER in doses of 4, 8, and 12 mg/day provided reductions in the frequency of partial-onset seizures compared with placebo. Percentage of patients achieving ≤ 50% reduction from baseline in seizure frequency/28 days on doses 4, 8 and 12 mg daily was 29%, 35% and 35% respectively vs. 19% in placebo group (p<0,01). Median% change from baseline in seizure frequency/28 days saw also more evident in PER group. Adverse events (AEs) occurred in 65-89% of patients receiving any dose of PER vs. 67% patients receiving placebo. Most AEs were of mild or moderate intensity (dose related). Most frequently reported AEs were dizziness, somnolence and aggression. 1218 pts were enrolled in the open-label extension study. 91% of patients reached 10 or 12 mg/day of PER. Efficacy was maintained with long-term treatment with responder rates of 62.7% during Weeks 92-104. Frequency and character of AEs were consistent with that in double blind phase.
  
  
  CONCLUSIONS
  The presented data indicate that PER at a daily dose of 4, 8 or 12 mg is efficacious as additional treatment of adolescents and adults with refractory partial seizures secondarily generalized and without generalization with acceptable tolerability.
authors.forename: E D
authors.initials: ED
authors.lastname: Belousova
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D009570:Nitriles; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel