Sustained Seizure Freedom with Perampanel 4 mg/day Monotherapy in Patients with Newly Diagnosed/Currently Untreated Recurrent Partial-Onset Seizures: Post Hoc Analysis of Study 342 (FREEDOM)
Abstract number :
556
Submission category :
7. Antiepileptic Drugs / 7B. Clinical Trials
Year :
2020
Submission ID :
2422897
Source :
www.aesnet.org
Presentation date :
12/6/2020 5:16:48 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Yuichi Kubota, TMG Asaka Medical Center; Ji Hyun Kim - Korea University Guro Hospital, Guro-gu, Seoul, Republic of Korea; Sung Chul Lim - St. Vincent's Hospital, The Catholic University of Korea; Hirotomo Ninomiya - Itami City Hospital; Takamichi Yamamoto
Rationale:
In the US and Japan, perampanel is approved for partial-onset seizures (POS; adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 years. FREEDOM (NCT03201900; Japan/South Korea) is a multicenter, open-label Phase III study of perampanel monotherapy in patients (aged 12–74 years) with newly diagnosed/currently untreated recurrent POS, with/without secondarily generalized seizures (SGS). We assessed if seizure freedom with perampanel 4 mg/day achieved during the Core Study is maintained during 52 weeks’ treatment.
Method:
The Core Study comprised 4 and 8 mg/day Treatment Phases. 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 (4-week Titration; 26-week Maintenance) in case of seizure. Patients completing the Core Study could enter an Extension Phase. Seizure-freedom rates for 52 weeks (Core and Extension Phases) at 4 mg/day for POS and based on seizure history were assessed in patients who were seizure free during the 4 mg/day Core Study Maintenance Period (calculated from the start of their seizure-free period). Treatment-emergent adverse events (TEAEs) were monitored.
Results:
Overall, 89 patients received ≥ 1 perampanel dose (Safety Analysis Set [SAS]). Of these, 73 patients entered the 4 mg/day Maintenance Period (modified Intent-to-Treat [mITT] population). Seizure-freedom for 26 weeks was achieved by 46/73 (63.0%) patients with POS during the 4 mg/day Maintenance Period. Of 46 patients, 20 (27.4% of the mITT population [n=20/73]) achieved sustained seizure freedom at 4 mg/day for 52 weeks; 5 patients were not considered seizure free due to not reaching the 26-week visit of the Extension at data cut-off. Seizure freedom was sustained for 52 weeks at 4 mg/day in 12/41 (29.3%) patients in the mITT who reported history of complex partial seizures (CPS), 19/70 (27.1%) patients with history of CPS and/or SGS, and 12/48 (25.0%) patients with history of SGS. Seventeen patients with history of SGS did not achieve 26 weeks’ seizure freedom, mainly due to discontinuations or experiencing other seizure types rather than lack of SGS control: 4 (23.5%) patients had no seizures but discontinued due to other reasons and 13 (76.5%) experienced ≥ 1 of the following seizure types so entered the 8 mg/day Treatment Phase: SGS, n=6 (35.3%); CPS, n=5 (29.4%); simple POS with/without motor signs, n=1 (5.9%) each. TEAEs occurred in 72 (80.9%) patients in the SAS across the Core and Extension Phase; most common were dizziness (36.0%), nasopharyngitis (19.1%), and somnolence (13.5%).
Conclusion:
These data suggest seizure freedom is sustained during long-term (52 weeks') treatment with perampanel monotherapy 4 mg/day in patients with newly diagnosed/currently untreated recurrent POS with/without SGS. Perampanel 4 mg/day was well tolerated during long-term treatment; no new TEAEs were reported.
Funding:
:
Funding:
: Eisai Co., Ltd.
Antiepileptic Drugs