Sustained Seizure Freedom with Perampanel 4 mg/day Monotherapy in Patients with Newly Diagnosed/Currently Untreated Focal-Onset Seizures: Study 342

초록

Purpose: FREEDOM (NCT03201900; Japan/South Korea) is a multicentre, open-label Phase III study of perampanel monotherapy in patients (aged 12–74 years) with newly diagnosed/currently untreated recurrent focal-onset seizures (FOS), with/without focal to bilateral tonic-clonic seizures (FBTCS). We assessed if seizure freedom with perampanel 4 mg/day achieved during the Core Study is maintained during 52 weeks’ treatment. Method: During the Core Study, patients received perampanel 4 mg/day (4-week Pretreatment; 32-week Treatment [6-week Titration; 26-week Maintenance]), with titration up to 8 mg/day in case of seizure. Patients completing the Core Study could enter an Extension Phase. Seizure-freedom rates for 52 weeks (Core/Extension Phases) at 4 mg/day for FOS and based on seizure history were assessed in patients who were seizure free during the 4-mg/day Core Study Maintenance Period. Treatment-emergent adverse events (TEAEs) were monitored. Results: Eighty-nine patients received ≥1 perampanel dose (Safety Analysis Set [SAS]) and 73 entered the Maintenance Period (modified Intent-to-Treat [mITT] population). Seizure freedom for 26 weeks was achieved by 46/73 (63.0%) patients with FOS during Maintenance. Of 32 patients who chose to enter the Extension Phase, 20 (62.5% [27.4% of the mITT population (n = 20/73)]) achieved sustained seizure freedom at 4 mg/day for 52 weeks; 4 patients had not completed 52 weeks of treatment at data cutoff. Based on patients in the mITT who entered the Extension Phase, >55% of patients with a history of focal impaired awareness seizures (FIAS), FIAS and/or FBTCS or FBTCS had sustained seizure freedom for 52 weeks on perampanel 4 mg/day. TEAEs occurred in 72 (80.9%) patients in the SAS (Core and Extension Phases); most common was dizziness (36.0%). Conclusion: Seizure freedom was sustained during long-term (52 weeks) treatment with perampanel monotherapy 4 mg/day in patients with newly diagnosed/currently untreated recurrent FOS with/without FBTCS. Perampanel 4 mg/day was well tolerated. Funding: Eisai Co., Ltd.