Assessment of the long-term efficacy and safety of adjunctive perampanel in tonic-clonic seizures: Analysis of four open-label extension studies.
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.
['Rektor|Ivan|I|0000-0002-9635-7404', 'Krauss|Gregory L|GL|0000-0002-0338-6039', 'Inoue|Yushi|Y|', 'Kaneko|Sunao|S|', 'Williams|Betsy|B|', 'Patten|Anna|A|', 'Malhotra|Manoj|M|', 'Laurenza|Antonio|A|', 'Wechsler|Robert T|RT|0000-0002-3146-986X']
D000293:Adolescent D000328:Adult D000927:Anticonvulsants D004244:Dizziness D004311:Double-Blind Method D004359:Drug Therapy, Combination D005260:Female D005500:Follow-Up Studies D006801:Humans D008297:Male D008875:Middle Aged D009570:Nitriles D011728:Pyridones D012640:Seizures D000077260:Sleepiness D013997:Time Factors D016896:Treatment Outcome D055815:Young Adult
focal to bilateral tonic-clonic seizures generalized tonic-clonic seizures AMPA receptor antagonist antiseizure medication