Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug 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 oral suspension (0.5 mg/mL) in pediatric patients (aged 4 to <12 years) with POS (with/without secondarily generalized seizures [SGS]) or PGTCS. Patients who completed the 311 Core Study could enter Extension Phase A. Here, we report the effect of adjunctive perampanel on cognition by responder status and modal dose at Week 23 and Week 52 compared with Baseline in Study 311 (Core and Extension). Methods: The Core Study comprised 4-week Pretreatment, 23-week Treatment (11-week Titration; 12-week Maintenance), and 4-week Follow-up (patients not entering Extension A) Periods. Extension A comprised 29-week Maintenance and 4-week Follow up Periods. This analysis included cumulative data from all enrolled patients (≤23 weeks [for those participating in the Core Study]; ≤52 weeks [for those participating in the Core and Extension Study]). Change from Baseline was assessed at Week 23 and 52 for cognitive function using the Aldenkamp-Baker neuropsychological assessment schedule (ABNAS) based on total seizure response category (<50%, ≥50%, ≥75%, 100% responder) and modal dose (<4, 4, >4–6, >6–8, >8–12, >12–16 mg/day). A high ABNAS score, on a 0–72 scale, reflects a high level of cognitive problems. Results: Of the 180 patients (mean [standard deviation, SD)] age, 8.1 [2.1] years; 48.9% female) enrolled in the Core Study, 136 entered Extension A. Fourteen (10.3%) patients discontinued from Extension A; the most common primary reason for discontinuation was adverse events (n=5 [3.7%]). For all 180 enrolled patients, mean (SD) duration of exposure of perampanel was 41.5 (17.3) weeks. Change from Baseline to Week 23 and Week 52 for ABNAS by responder status is presented in Table 1. Based on responder status, total mean (SD) change in ABNAS score from Baseline was as follows for Week 23 and Week 52: <50% responders, 3.7 (11.5) and -3.2 (16.8); ≥50% responders, -4.7 (13.8) and -3.7 (18.4); ≥75% responders, -2.1 (11.4) and -4.2 (14.8); 100% responders, -1.6 (18.3) and -0.6 (20.6), respectively. Table 2 presents change from Baseline to Week 23 and Week 52 for ABNAS by modal dose. Total mean (SD) change from Baseline in ABNAS at Week 23 and Week 52 by modal dose was as follows: <4 mg, -5.8 (7.3) and -2.0 (7.2); 4 mg, -4.8 (22.4) and -10.4 (25.6); >4–6 mg, 1.3 (8.3) and -1.3 (10.2); >6–8 mg, -0.5 (10.7) and 1.9 (9.4); >8–12 mg, -0.1 (12.8) and -7.4 (20.2); >12–16 mg, 2.2 (12.4) and 1.1 (14.8), respectively. Conclusions: These data suggest that adjunctive perampanel has few overall long-term effects on cognition in pediatric patients (aged 4 to <12 years) with POS (with/without SGS) or PGTCS, regardless of responder status and modal dose. Funding: Eisai Inc.