Yamamoto Takamichi, Lim Sung Chul, Ninomiya Hirotomo, Kubota Yuichi, Shin Won Chul, Kim Dong Wook, Shin Dong Jin, Iida Koji, Ochiai Taku, Matsunaga Risa, Hiramatsu Hidetaka, Kim Ji Hyun
Seirei Mikatahara General Hospital, Hamamatsu, Japan.
The Catholic University of Korea, St. Vincent's Hospital, Suwon, Republic of Korea.
Epilepsy Res. 2025 Feb;210:107494. doi: 10.1016/j.eplepsyres.2024.107494. Epub 2024 Dec 20.
FREEDOM (Study 342; NCT03201900) assessed the long-term treatment effect of perampanel monotherapy in adolescent and adult patients (12-74 years of age) with untreated focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS).
In the Core Study, after a 4-week Pretreatment Phase, perampanel was up-titrated to 4 mg/day during a 6-week Titration Period followed by a 26-week Maintenance Period. Patients experiencing seizure(s) during the 4-mg/day Maintenance Period could have perampanel up-titrated to 8 mg/day over 4 weeks then could enter the 26-week 8-mg/day Maintenance Period. Patients could enter Extension to continue treatment upon the completion of the Core Study. Seizure-freedom rates, time to seizure recurrence or withdrawal since the initiation of maintenance treatment, and safety outcomes were assessed.
In FREEDOM, 89 patients who received ≥ 1 perampanel dose were included for safety assessments (Safety Analysis Set), and 73 of them entered the 4-mg/day Maintenance Period (the modified Intent-to-Treat Analysis set) with 21 patients having perampanel up-titrated to 8 mg/day; 46 patients entered Extension with 38 patients completing. Overall, 42/89 (47.2 %) patients had cumulative exposure to perampanel for > 52 weeks. Among patients who entered Extension, 52.2 % (n = 24/46; 95 % confidence interval [CI] 36.9, 67.1) remained seizure free for 52 weeks at perampanel 4 mg/day and 67.4 % (n = 31/46; 95 % CI 52.0, 80.5) at 4-8 mg/day. The cumulative probabilities of seizure recurrence and withdrawal at 4-8 mg/day over 52 weeks were 28.9 % (95 % CI 19.0, 42.4) and 43.8 % (95 % CI 33.4, 55.9), respectively. Treatment-emergent adverse events (TEAEs) occurred in 74/89 (83.1 %) patients, with 9/89 (10.1 %) discontinuing because of TEAEs. Dizziness occurred in 34/89 (38.2 %) patients and was the most common event.
Patients with untreated FOS (with or without FBTCS) are able to maintain seizure freedom for up to 52 weeks with perampanel monotherapy at a dose of 4-8 mg/day. The tolerability profile was manageable, and the safety profile was consistent with previous findings.
FREEDOM（研究342；NCT03201900）评估了吡仑帕奈单药治疗对未治疗的局灶性发作（FOS）的青少年和成年患者（12 - 74岁）的长期治疗效果，这些患者伴有或不伴有从局灶性发作发展为双侧强直阵挛发作（FBTCS）。
在核心研究中，经过4周的预处理阶段后，吡仑帕奈在6周的滴定期内逐渐滴定至4毫克/天，随后是26周的维持期。在4毫克/天维持期内出现发作的患者，吡仑帕奈可在4周内逐渐滴定至8毫克/天，然后可进入26周的8毫克/天维持期。患者在核心研究完成后可进入延长期继续治疗。评估无癫痫发作率、自维持治疗开始至癫痫复发或停药的时间以及安全性结果。
在FREEDOM研究中，89例接受过≥1剂吡仑帕奈的患者被纳入安全性评估（安全性分析集），其中73例进入4毫克/天维持期（改良意向性治疗分析集），21例患者的吡仑帕奈剂量滴定至8毫克/天；46例患者进入延长期，38例完成延长期治疗。总体而言，42/89（47.2%）例患者累计接受吡仑帕奈治疗>52周。在进入延长期的患者中，52.2%（n = 24/46；95%置信区间[CI]36.9，67.1）在吡仑帕奈4毫克/天剂量下52周无癫痫发作，在4 - 8毫克/天剂量下为67.4%（n = 31/46；95%CI 52.0，80.5）。在4 - 8毫克/天剂量下52周内癫痫复发和停药的累积概率分别为28.9%（95%CI 19.0，42.4）和43.8%（95%CI 33.4，55.9）。74/89（83.1%）例患者发生治疗中出现的不良事件（TEAE），9/89（10.1%）例因TEAE停药。34/89（38.2%）例患者出现头晕，是最常见的事件。
未治疗的FOS（伴有或不伴有FBTCS）患者使用4 - 8毫克/天剂量的吡仑帕奈单药治疗能够维持长达52周的无癫痫发作状态。耐受性情况可控，安全性情况与既往研究结果一致。
