title: Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study.
abstract: OBJECTIVE
  Assess perampanel's efficacy and safety as adjunctive therapy in adolescents (ages 12-17) with drug-resistant partial seizures.
  
  
  METHODS
  Adolescent patients enrolled in multinational, double-blind, placebo-controlled, phase III core studies (studies 304, 305, or 306) completed 19-week, double-blind phase (6-week titration/13-week maintenance) with once-daily perampanel or placebo. Upon completion, patients were eligible for the extension (study 307), beginning with 16-week, blinded conversion, during which placebo patients switched to perampanel. Patients then entered the open-label treatment.
  
  
  RESULTS
  Of 1480 patients from the core studies, 143 were adolescents. Pooled adolescent data from these core studies demonstrated median percent decreases in seizure frequency for perampanel 8 mg (34.8%) and 12 mg (35.6%) were approximately twice that of placebo (18.0%). Responder rates increased with perampanel 8 mg (40.9%) and 12 mg (45.0%) versus placebo (22.2%). Adolescents receiving concomitant enzyme-inducing antiepileptic drugs (AEDs) had smaller reductions in seizure frequency (8 mg:31.6%; 12 mg:26.8%) than those taking non-inducing AEDs (8 mg:54.6%; 12 mg:52.7%). Relative to pre-perampanel baseline, seizure frequency and responder rates during the extension (Weeks 1-52) improved with perampanel. Most commonly reported adverse events in adolescents during the core studies were dizziness (20.4%), somnolence (15.3%), aggression (8.2%), decreased appetite (6.1%), and rhinitis (5.1%). Dizziness (13.2%), somnolence (11.6%), and aggression (6.6%) most often led to perampanel interruption/dose adjustment during the extension.
  
  
  CONCLUSIONS
  Data demonstrated adjunctive perampanel treatment in adolescents with drug-resistant partial seizures produced better seizure control versus placebo, sustained seizure frequency improvements, and a generally favorable safety profile. Results were comparable to the overall study population.
  
  
  BACKGROUND
  clinicaltrials.gov Identifiers: Study 304: NCT00699972; 305: NCT00699582; 306: NCT00700310; Study 307: NCT00735397.
authors.affiliation: Comprehensive Epilepsy Care Center for Children and Adults, St Louis, MO, USA. Electronic address: werosenfeld@msn.com.
authors.forename: William
authors.initials: W
authors.lastname: Rosenfeld
authors.affiliation: Children's National Medical Center, Washington, DC, USA. Electronic address: jconry@childrensnational.org.
authors.forename: Joan
authors.initials: J
authors.lastname: Conry
authors.affiliation: University Hospitals KULeuven, Leuven, Belgium. Electronic address: lieven.lagae@uzleuven.be.
authors.forename: Lieven
authors.initials: L
authors.lastname: Lagae
authors.affiliation: Children's Clinical University Hospital, Riga, Latvia. Electronic address: dr.rozentals@inbox.lv.
authors.forename: Guntis
authors.initials: G
authors.lastname: Rozentals
authors.affiliation: Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA. Electronic address: Haichen_Yang@eisai.com.
authors.forename: Haichen
authors.initials: H
authors.lastname: Yang
authors.affiliation: Eisai Medical and Scientific Affairs, Woodcliff Lake, NJ, USA. Electronic address: Randi_Fain@eisai.com.
authors.forename: Randi
authors.initials: R
authors.lastname: Fain
authors.affiliation: Eisai Medical and Scientific Affairs, Woodcliff Lake, NJ, USA. Electronic address: Betsy_Williams@eisai.com.
authors.forename: Betsy
authors.initials: B
authors.lastname: Williams
authors.affiliation: Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA. Electronic address: Dinesh_Kumar@eisai.com.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Formerly Eisai Inc., Woodcliff Lake, NJ, USA. Electronic address: vgo329@yahoo.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA. Electronic address: Antonio_Laurenza@eisai.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Laurenza
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / 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 / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel
keywords: Adolescent; Antiepileptic drugs; Epilepsy; Perampanel; Post hoc analysis