Assessment of the long-term efficacy and safety of adjunctive perampanel in tonic-clonic seizures: Analysis of four open-label extension studies

Ivan Rektor, Gregory L. Krauss, Yushi Inoue, Sunao Kaneko, Betsy Williams, Anna Patten, Manoj Malhotra, Antonio Laurenza, Robert T. Wechsler

Research output: Contribution to journalArticle

Abstract

Objective: This post hoc analysis evaluated long-term efficacy and safety in patients with focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who entered open-label extension (OLEx) studies to receive long-term adjunctive perampanel. Methods: Patients aged 12 years and older who completed phase II or III randomized, double-blind, placebo-controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open-label maintenance period (32-424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed. Results: Baseline characteristics were generally balanced between patients with FBTCS (n = 720) and GTCS (n = 138). Mean (standard deviation) cumulative duration of perampanel exposure was 102.3 (70.3) weeks (FBTCS) and 83.9 (38.4) weeks (GTCS). Retention rates were 50.0% for up to 4 years (FBTCS) and 49.2% for up to 2 years (GTCS). Across OLEx treatment durations, median reductions in seizure frequency per 28 days were 66.7% (FBTCS) and 80.6% (GTCS). Fifty percent and 75% responder and seizure-freedom rates were 59.5%, 45.3%, and 18.4%, respectively (FBTCS), and 72.5%, 51.5%, and 16.7%, respectively (GTCS). Efficacy was sustained for up to 4 years (FBTCS) and up to 3 years (GTCS), even when accounting for early dropouts. TEAE incidence was highest during Year 1 (FBTCS, 85.3%; GTCS, 86.2%); most common were dizziness and somnolence. During Year 1, serious TEAEs were reported in 81 (11.3%; FBTCS) and 10 (7.2%; GTCS) patients. TEAEs were consistent with the known safety profile of perampanel; no new safety signals were identified with long-term treatment. Significance: This post hoc analysis suggests long-term (up to 4 years) adjunctive perampanel (up to 12 mg/d) is efficacious and well tolerated in patients (aged 12 years and older) with FBTCS or GTCS.

Original languageEnglish (US)
Pages (from-to)1491-1502
Number of pages12
JournalEpilepsia
Volume61
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • AMPA receptor antagonist
  • antiseizure medication
  • focal to bilateral tonic-clonic seizures
  • generalized tonic-clonic seizures

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Rektor, I., Krauss, G. L., Inoue, Y., Kaneko, S., Williams, B., Patten, A., Malhotra, M., Laurenza, A., & Wechsler, R. T. (2020). Assessment of the long-term efficacy and safety of adjunctive perampanel in tonic-clonic seizures: Analysis of four open-label extension studies. Epilepsia, 61(7), 1491-1502. https://doi.org/10.1111/epi.16573