Efficacy and safety of perampanel monotherapy in patients with focal-onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: The open-label Study 342 (FREEDOM Study)

Takamichi Yamamoto; Sung Chul Lim; Hirotomo Ninomiya; Yuichi Kubota; Won Chul Shin; Dong Wook Kim; Dong Jin Shin; Tohru Hoshida; Koji Iida; Taku Ochiai; Risa Matsunaga; Hiroyuki Higashiyama; Hidetaka Hiramatsu; Ji Hyun Kim

doi:10.1002/epi4.12398

Efficacy and safety of perampanel monotherapy in patients with focal-onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: The open-label Study 342 (FREEDOM Study)

Epilepsia Open. 2020 Jun 7;5(2):274-284. doi: 10.1002/epi4.12398. eCollection 2020 Jun.

Authors

Takamichi Yamamoto¹, Sung Chul Lim², Hirotomo Ninomiya³, Yuichi Kubota^{4

5}, Won Chul Shin⁶, Dong Wook Kim⁷, Dong Jin Shin⁸, Tohru Hoshida^{9

10}, Koji Iida¹¹, Taku Ochiai¹², Risa Matsunaga¹³, Hiroyuki Higashiyama¹⁴, Hidetaka Hiramatsu¹³, Ji Hyun Kim¹⁵

Affiliations

¹ Seirei Hamamatsu General Hospital Hamamatsu Japan.
² The Catholic University of Korea St. Vincent Hospital Gyeonggi-do Republic of Korea.
³ Itami City Hospital Hyogo Japan.
⁴ TMG Asaka Medical Center Saitama Japan.
⁵ Present address: Tokyo Women's Medical University Medical Center East Tokyo Japan.
⁶ Kyung Hee University Hospital at Gangdong Seoul Republic of Korea.
⁷ Konkuk University School of Medicine Seoul Republic of Korea.
⁸ Gachon University Gil Medical Center Incheon Republic of Korea.
⁹ National Hospital Organization Nara Medical Center Nara Japan.
¹⁰ Present address: Takanohara Central Hospital Nara Japan.
¹¹ Hiroshima University Hiroshima Japan.
¹² Ochiai Neurological Clinic Saitama Japan.
¹³ Eisai Co., Ltd. Tokyo Japan.
¹⁴ Formerly: Eisai Co., Ltd. Tokyo Japan.
¹⁵ Korea University Guro Hospital Seoul Republic of Korea.

Abstract

Objective: Our study assessed perampanel monotherapy in patients (aged ≥12 years) with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures (FBTCS) in Japan and South Korea.

Methods: Study 342 (NCT03201900; FREEDOM) is a single-arm, open-label, Phase III study. Patients initially received perampanel in a 32-week 4-mg/d Treatment Phase (6-week Titration; 26-week Maintenance Periods). If they experienced a seizure during the 4-mg/d Maintenance Period, they could be up-titrated to 8 mg/d across an additional 30-week Treatment Phase (4-week Titration; 26-week Maintenance Periods). Primary endpoint was the seizure-freedom rate during the Maintenance Period (4 mg/d and last evaluated dose [4 or 8 mg/d]). Secondary endpoints included time to first seizure onset and to withdrawal during Maintenance. Treatment-emergent adverse events (TEAEs) were monitored.

Results: At data cutoff (February 28, 2019), 89 patients with FOS (84 [94.4%] with newly diagnosed epilepsy and 5 [5.6%] with recurrence of epilepsy after a period of remission) had received ≥1 perampanel dose; 16 patients discontinued during the 4-mg/d Titration Period, meaning 73 patients entered the 4-mg/d Maintenance Period and were included in the primary analysis set for efficacy. Seizure-freedom rate in the 26-week Maintenance Period was 46/73 (63.0%; 95% confidence interval [CI]: 50.9-74.0) at 4 mg/d and 54/73 (74.0%; 95% CI: 62.4-83.5) at 4 or 8 mg/d. Cumulative probability of seizure-onset and withdrawal rates during Maintenance was 30.8% (95% CI: 21.5-43.0) and 23.7% (95% CI: 15.4-35.3) at 4 mg/d, and 18.2% (95% CI: 11.0-29.3) and 23.3% (95% CI: 15.2-34.8) at 4 or 8 mg/d. Perampanel was generally well tolerated, and the most common TEAE was dizziness.

Significance: Perampanel monotherapy (4 to 8 mg/d) was efficacious and consistent with the known safety profile up to 26 weeks in patients (≥12 years) with primarily newly diagnosed FOS with or without FBTCS.

Keywords: antiepileptic drug; focal‐onset seizures; monotherapy; perampanel; seizure freedom.