Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug (ASD) for partial-onset seizures (POS) and primary generalized tonic-clonic seizures (PGTCS). Study 311 (NCT02849626) was a multicenter, open-label, single-arm study of perampanel (0.5 mg/mL) in pediatric patients (pts; aged 4 to <12 years) with POS (with/without secondarily generalized seizures [SGS]) or PGTCS. Pts completing the Core Study could enter Extension Phase A. We report safety and efficacy data by Baseline concomitant enzyme-inducing ASD (EIASD) status in Study 311 (Core and Extension). EIASDs were defined as carbamazepine, eslicarbazepine, oxcarbazepine, and phenytoin. Methods: The Core Study comprised 4-week Pretreatment, 23-week Treatment (11-week Titration; 12-week Maintenance), and 4-week Follow-up (pts not entering Extension) Periods. Extension A comprised 29-week Maintenance and 4-week Follow-up Periods. Pts could receive 1–3 concomitant ASDs; 1 EIASD was permitted. Perampanel was titrated to ≤12 mg/day (without EIASDs or pts in Japan) or ≤16 mg/day (with EIASDs). This analysis included cumulative data from all enrolled pts (≤23 weeks [for those participating in the Core Study]; ≤52 weeks [for those participating in the Core and Extension Study]). Assessments included monitoring treatment-emergent adverse events (TEAEs), median percent change in seizure frequency/28 days from Baseline, and 50% responder and seizure-freedom rates across the Treatment Period. Results: Of 180 pts enrolled in the Core Study (with EIASDs, n=48; without EIASDs, n=132), 136 pts entered Extension A (with EIASDs, n=34; without EIASDs, n=102). During Extension A, adverse events led to the discontinuation of 2.9% of pts with EIASDs and 3.9% of pts without EIASDs; inadequate therapeutic effect led to the discontinuation of 0% and 3.9% of pts, respectively. For all 180 enrolled pts, mean (standard deviation) duration of exposure was 40.8 (17.7) and 41.8 (17.2) weeks with/without EIASDs, respectively. Of pts taking an EIASD, carbamazepine was most common (n=25 [52.1%]). Two pts with PGTCS received concomitant EIASDs; however, they were not included in the efficacy analysis as neither had PGTCS at Baseline. An overview of TEAEs is presented in Table 1; most common were somnolence and nasopharyngitis. Median percent reductions in POS and SGS frequencies/28 days are shown in Figure 1. Fifty-percent responder rates during Weeks 1–13 were maintained during Weeks 40–52 with EIASDs (POS: 21/46 [45.7%] and 21/32 [65.6%]; SGS: 8/11 [72.7%] and 5/6 [83.3%], respectively) and without EIASDs (POS: 47/102 [46.1%] and 46/76 [60.5%]; SGS: 26/43 [60.5%] and 28/35 [80.0%], respectively). Seizure-freedom rates for POS and SGS at Weeks 40–52 were: 7/32 (21.9%) and 2/6 (33.3%) with EIASDs; and 7/76 (9.2%) and 8/35 (22.9%) without EIASDs, respectively. Conclusions: These data suggest long-term (≤52 weeks) adjunctive perampanel is generally well tolerated and efficacious in pts aged 4 to <12 years with POS with/without SGS, regardless of EIASD status. Funding: Eisai Inc.