title: Perampanel for adjunctive treatment of partial-onset seizures: a pooled dose-response analysis of phase III studies.
abstract: OBJECTIVE
  To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed.
  
  
  METHODS
  Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9% of the treated cohort).
  
  
  RESULTS
  Of 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from -32.4% (8 mg, phase III Maintenance Period) to -44.2% (12 mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1-13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension.
  
  
  CONCLUSIONS
  Increasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.
authors.affiliation: Eisai Neuroscience and General Medicine Product Creation Unit, Eisai Inc, Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Kramer
authors.forename: Andrew
authors.initials: A
authors.lastname: Satlin
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Krauss
authors.forename: Jacqueline
authors.initials: J
authors.lastname: French
authors.forename: Emilio
authors.initials: E
authors.lastname: Perucca
authors.forename: Elinor
authors.initials: E
authors.lastname: Ben-Menachem
authors.forename: Patrick
authors.initials: P
authors.lastname: Kwan
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Shih
authors.forename: Antonio
authors.initials: A
authors.lastname: Laurenza
authors.forename: Haichen
authors.initials: H
authors.lastname: Yang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: David
authors.initials: D
authors.lastname: Squillacote
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004244:Dizziness / Q000139:chemically induced / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel
keywords: Actual (last) dose; Antiepileptic; Efficacy; Epilepsy; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid