title: Perampanel for tonic-clonic seizures in  idiopathic generalized epilepsy  A randomized trial.
abstract: OBJECTIVE
  To assess efficacy and safety of adjunctive perampanel in patients with drug-resistant, primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE).
  
  
  METHODS
  In this multicenter, double-blind study (ClinicalTrials.gov identifier: NCT01393743; funded by Eisai Inc.), patients 12 years or older with PGTC seizures and IGE were randomized to placebo or perampanel during a 4-week titration period (perampanel up titrated from 2 to 8 mg/d, or highest tolerated dose) and 13-week maintenance period. The primary endpoint was percent change in PGTC seizure frequency per 28 days (titration plus maintenance vs baseline). The key secondary endpoint (primary endpoint for European Union registration) was 50% PGTC seizure responder rate (patients achieving $50% reduction in PGTC seizure frequency; maintenance vs baseline). Treatment-emergent adverse events were monitored.
  
  
  RESULTS
  Of 164 randomized patients, 162 comprised the full analysis set (placebo, 81; perampanel, 81). Compared with placebo, perampanel conferred a greater median percent change in PGTC seizure frequency per 28 days (238.4%vs 276.5%; p , 0.0001) and greater 50%PGTC seizure responder rate (39.5% vs 64.2%; p 5 0.0019). During maintenance, 12.3% of placebo treated patients and 30.9%of perampanel-treated patients achieved PGTC seizure freedom. For the safety analysis (placebo, 82; perampanel, 81), the most frequent treatment-emergent adverse events with perampanel were dizziness (32.1%) and fatigue (14.8%).
  
  
  CONCLUSIONS
  Adjunctive perampanel was well tolerated and improved control of drug-resistant PGTC seizures in patients with IGE.
  
  
  METHODS
  This study provides Class I evidence that adjunctive perampanel reduces PGTC seizure frequency, compared with placebo, in patients with drug-resistant PGTC seizures in IGE.
authors: Jacqueline A
authors: JA
authors: French
authors: Gregory L
authors: GL
authors: Krauss
authors: Robert T
authors: RT
authors: Wechsler
authors: Xue-Feng
authors: XF
authors: Wang
authors: Bree
authors: B
authors: DiVentura
authors: Christian
authors: C
authors: Brandt
authors: Eugen
authors: E
authors: Trinka
authors: Terence J
authors: TJ
authors: O'Brien
authors: Antonio
authors: A
authors: Laurenza
authors: Anna
authors: A
authors: Patten
authors: Francesco
authors: F
authors: Bibbiani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D004829:Epilepsy, Generalized / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011728:Pyridones / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel