title: Analysis of falls in patients with epilepsy enrolled in the perampanel phase III randomized double-blind studies.
abstract: To analyze occurrence of falls among patients with partial seizures, with/without secondarily generalized seizures (SGS), and primary generalized tonic-clonic seizures (PGTCS) in the perampanel phase III clinical studies.
  
  
  
  Studies 304, 305, and 306 randomized subjects (≥12 years) with drug-resistant partial seizures (with/without SGS) to perampanel 2, 4, 8, or 12 mg or placebo for double-blind treatment. The adverse event (AE) of falls was analyzed in the Safety Analysis Set (N = 1480). Study 332 randomized subjects aged ≥12 years with a diagnosis of PGTCS into perampanel 8 mg or placebo groups for double-blind treatment. In a systematic review of reported falls in the study 332 Safety Analysis Set (N = 163), falls were queried to establish whether each was seizure related; subjects with falls resulting from a seizure were not included in this analysis.
  
  
  
  For studies 304/305/306, treatment-emergent falls occurred in 5.1% perampanel-treated versus 3.4% placebo-treated subjects with partial seizures. Exposure-adjusted rate for falls (falls/subject-month of exposure) was greater for total perampanel than for placebo (0.0175 vs. 0.0093) and was dose related for those receiving perampanel. In subjects with SGS, incidence of treatment-emergent falls was 4.3% in perampanel and 4.0% in placebo groups. Exposure-adjusted rates were 0.0169 and 0.0097 falls per subject-month of exposure in perampanel and placebo, respectively. For study 332, 2.5% perampanel-treated and 1.2% placebo-treated subjects with PGTCS had treatment-emergent falls that were not part of a seizure. Exposure-adjusted rates were 0.0169 and 0.0032 falls per subject-month of exposure in perampanel and placebo, respectively.
  
  
  
  Results of the perampanel studies suggest that patients with epilepsy should be monitored due to the common risk of falls.
authors.affiliation: Department of Neurology and College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, U.S.A.
authors.forename: Ilo E
authors.initials: IE
authors.lastname: Leppik
authors.affiliation: Formerly of Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Haichen
authors.initials: H
authors.lastname: Yang
authors.affiliation: Eisai Medical and Scientific Affairs, Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Betsy
authors.initials: B
authors.lastname: Williams
authors.affiliation: Eisai Medical and Scientific Affairs, Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Sharon
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Formerly of Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Randi
authors.initials: R
authors.lastname: Fain
authors.affiliation: Eisai Ltd., Hatfield, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Patten
authors.affiliation: Eisai Neuroscience and General Medicine PCU, Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bibbiani
authors.affiliation: Eisai Neuroscience and General Medicine PCU, Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Antonio
authors.initials: A
authors.lastname: Laurenza
mesh_terms: D000058:Accidental Falls; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011728:Pyridones / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel
keywords: Antiepileptic drugs; Falls; Partial seizures; Perampanel; Primary generalized tonic-clonic seizures