Abstracts

Rationale: Perampanel is a once-daily oral antiepileptic drug (AED) for POS and PGTCS. Study 311 (NCT02849626) assessed the safety, tolerability, pharmacokinetics, and efficacy of adjunctive perampanel for the treatment of POS (with/without secondarily generalized seizures [SGS]) or PGTCS in pediatric patients aged 4 to ?12 years. Here, we report interim data (data cut-off: January 31, 2018) from the Core Study. Methods: Study 311 is a global, multicenter, open-label, single-arm study of perampanel oral suspension in pediatric patients with inadequately controlled POS or PGTCS. The Core Study consists of a 4-week Pre-treatment Period (Screening/Baseline), 23-week Treatment Period (11 weeks Titration; 12 weeks Maintenance), and a 4-week Follow-up Period. Study endpoints include safety and tolerability of perampanel (primary endpoint), median percent change in seizure frequency per 28 days from Baseline during the Treatment Period (secondary endpoint), and 50% responder rates and seizure-free status during the Maintenance Period (of the Core Study) and during longer-term treatment (=52 weeks; secondary endpoint). Perampanel oral suspension (0.5 mg/mL) was administered once daily at bedtime. Perampanel dose and titration schedule were based on clinical response and tolerability, and whether patients were taking a concomitant enzyme-inducing AED. Results: At data cut-off, 161 patients (POS, n=135; PGTCS, n=26) received at least one dose of perampanel (mean [standard deviation] patient age, 8.2 [2.1] years; female, 47.1%). A total of 56 patients were ongoing, 77 had completed the Core Study (of whom 73 had entered the Extension Study), and 28 had discontinued. Primary reasons for discontinuation were adverse events (n=11 [6.8%] patients), patient choice (n=7 [4.3%]), inadequate therapeutic effect (n=5 [3.1%]), withdrawal of consent (n=2 [1.2%]), and ‘other’ (n=3 [1.9%]). The median (minimum [min], maximum [max]) daily dose of perampanel across all patients included in the Safety Analysis Set (N=157) was 6.0 (2, 16) mg/day, and the median (min, max) duration of exposure was 20.1 (0, 24) weeks. An overview of treatment-emergent adverse events (TEAEs), including central nervous system-related TEAEs, is presented in Table 1. The most common TEAEs (occurring in =10% of patients) were somnolence, nasopharyngitis, dizziness, and irritability. In patients with POS, with/without SGS, or PGTCS, there was an improvement from Baseline in seizure frequency per 28 days (Figure 1A). Figure 1B shows 50% responder rates at assessment and the proportion of patients who achieved seizure-free status. Conclusions: This interim analysis suggests that daily oral doses of adjunctive perampanel are generally safe, well tolerated, and efficacious in children aged 4 to ?12 years with POS, SGS, or PGTCS. Funding: Eisai Inc.