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

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.

• Authors: Ivan Rektor, Gregory L Krauss, Yushi Inoue, Sunao Kaneko, Betsy Williams, Anna Patten, Manoj Malhotra, Antonio Laurenza, Robert T Wechsler
• Journal: Epilepsia (Epilepsia) Vol. 61 Issue 7 Pg. 1491-1502 (07 2020) ISSN: 1528-1167 [Electronic] United States
• PMID: 32645213 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Chemical References

• Anticonvulsants
• Nitriles
• Pyridones
• perampanel

Topics

• Adolescent
• Adult
• Anticonvulsants (administration & dosage, adverse effects)
• Dizziness (chemically induced)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Nitriles
• Pyridones (administration & dosage, adverse effects)
• Seizures (diagnosis, drug therapy, epidemiology)
• Sleepiness
• Time Factors
• Treatment Outcome
• Young Adult