Long-term tolerability, safety and efficacy of adjunctive perampanel in the open-label, dose-ascending Study 231 and extension Study 233 in Japanese patients with epilepsy

Naotaka Usui, Naoki Akamatsu, Nobukazu Nakasato, Akihiro Ohnishi, Sunao Kaneko, Hidetaka Hiramatsu, Kazunori Saeki, Hideaki Miyagishi, Yushi Inoue

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Purpose: To evaluate long-term tolerability, safety and efficacy of adjunctive perampanel in a Phase II, multicentre, open-label, dose-ascending Study 231 (NCT00849212) and its extension (Study 233; NCT00903786) in Japanese patients with refractory partial-onset seizures (POS), with/without secondarily generalised seizures. Methods: In Study 231, patients received adjunctive perampanel ≤12 mg/day during a 10-week treatment period. Patients completing Study 231 could enter Study 233 (≤316-week treatment period). Assessments included monitoring of treatment-related treatment-emergent adverse events (TEAEs), median percent change in seizure frequency per 28 days, 50% responder and seizure-freedom rates. During Study 231, a pharmacokinetic analysis assessed the effects of enzyme-inducing antiepileptic drugs. Results: Overall, 23/30 (76.7%) patients completed Study 231; 21/30 (70.0%) received perampanel ≥8 mg/day and 10/30 (33.3%) achieved a maximum tolerated dose of 12 mg/day. Median percent change in seizure frequency per 28 days was –35.0%. 50% responder rate was 37.0%; 4 (13.3%) patients achieved seizure freedom. Twenty-one patients entered Study 233. Mean duration of exposure was 195 weeks; 9 (42.9%) patients received perampanel for ≤208 weeks. Seizure control was sustained for 316 weeks in 3/21 (14.3%) patients; 2 achieved seizure freedom. Treatment-related TEAEs were tolerable; the most common was dizziness (Study 231, 53.3%; Study 233, 14.3%). Mean perampanel plasma concentrations were lower with concomitant carbamazepine vs non-inducers (152.7 ng/mL vs 389.4 ng/mL across perampanel groups); small patient numbers for non-inducers (n = 2) should be considered when interpreting these data. Conclusion: Adjunctive perampanel demonstrated a favourable safety profile and long-term tolerability in Japanese patients with refractory POS for ≤316 weeks.

Original languageEnglish
Pages (from-to)26-32
Number of pages7
JournalSeizure
Volume62
DOIs
Publication statusPublished - 2018 Nov

Keywords

  • AMPA receptor
  • Antiepileptic drugs
  • Epilepsy
  • Perampanel

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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