(346) Long-Term (52 weeks) Safety of Adjunctive Perampanel Based on Weight and Dose in Japanese Pediatric Patients (Aged 4 to <12 Years) with Partial-Onset Seizures in Study 311
Associate Professor, Department of Pediatrics, Vice Director of Epilepsy Center Hokkaido University Hospital
Rationale: In the U.S. 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 (PGTCS) in patients aged ≥ 12 years. Study 311 (NCT02849626) was a multicenter, open-label, single-arm study of perampanel oral suspension in pediatric patients (aged 4 to < 12 years) with POS (with or without secondarily generalized seizures [SGS]) or PGTCS. This post hoc analysis was performed to evaluate if there is any correlation between body weight and perampanel’s safety profile with respect to treatment-emergent adverse events (TEAEs) or perampanel modal dose in Study 311 (Core and Extension A) in Japanese patients with POS, with or without SGS. Methods: Patients completing the 27-week Core Study (4-week Pretreatment; 23-week Treatment [11-week Titration; 12-week Maintenance]) could enter Extension A (29-week Maintenance; 4-week Follow-up); maximum perampanel dose of 12 mg/day. Relationships between baseline body weight, perampanel modal dose, and TEAEs were assessed. Cumulative data from all enrolled patients are included until their exit point. Only patients with POS were enrolled in Japan. Results: Of 65 Japanese patients with POS enrolled in the Core Study, 53 entered Extension A; 50 patients completed Extension A and 3 discontinued due to patient choice, inadequate therapeutic effect, and withdrawal of consent (n=1 each). Mean (standard deviation [SD]) modal dose was 6.8 (3.0) mg/day across the Core and Extension A Phases. For all 65 enrolled patients, the overall median (range) body weight at baseline was 22.0 (16.1–49.7) kg. When stratified by modal dose, median (range) body weight was: 2 mg/day, 19.8 (16–41) kg; 4 mg/day, 24.2 (16–45) kg; 6 mg/day, 23.8 (17–48) kg; 8 mg/day, 23.7 (18–50) kg; 10 mg/day, 20.0 (17–34) kg; and 12 mg/day, 19.7 (17–38) kg. Across the Core Study and Extension A, treatment-related TEAEs occurred in 34 (52.3%) patients; the most common were somnolence (n=18 [27.7%]), dizziness (n=11 [16.9%]), and irritability (n=11 [16.9%]). No relationships were found between baseline weight, modal dose, and patients with somnolence, dizziness, and/or irritability (Figures 1A–C). Conclusions: Based on these data, there is no relationship between baseline body weight and safety outcomes or perampanel modal dose in Japanese pediatric patients (aged 4 to < 12 years) with POS, with or without SGS, following long-term (52 weeks') adjunctive perampanel treatment. Funding: Please list any funding that was received in support of this abstract.:
