Analysis of falls in patients with epilepsy enrolled in the perampanel phase III randomized double-blind studies

Ilo E. Leppik, Haichen Yang, Betsy Williams, Sharon Zhou, Randi Fain, Anna Patten, Francesco Bibbiani, Antonio Laurenza

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Objective: 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. Methods: 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. Results: 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. Significance: Results of the perampanel studies suggest that patients with epilepsy should be monitored due to the common risk of falls.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalEpilepsia
Volume58
Issue number1
DOIs
StatePublished - Jan 1 2017

Bibliographical note

Funding Information:
Editorial support was provided by Imprint Science, New York, NY, U.S.A., and was funded by Eisai Inc. This study was funded by Eisai Inc.

Publisher Copyright:
Wiley Periodicals, Inc. © 2016 International League Against Epilepsy

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Antiepileptic drugs
  • Falls
  • Partial seizures
  • Perampanel
  • Primary generalized tonic–clonic seizures

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