Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug (ASD) for POS and primary generalized tonic-clonic seizures (PGTCS). Randomized doses of adjunctive perampanel 4–12 mg/day have shown efficacy and tolerability in a pooled analysis of three Phase III studies (304, NCT00699972; 305, NCT00699582; 306, NCT00700310) in patients aged ≥12 years with POS, with/without secondarily generalized seizures (SGS). Study 311 (NCT02849626) was a multicenter, open-label, single-arm study of perampanel oral suspension (0.5 mg/mL; up to 12 mg/day without enzyme-inducing ASDs [EIASDs] or up to 16 mg/day with EIASDs) in patients aged 4 to <12 years with POS (with/without SGS) or PGTCS. Here, we present efficacy and safety data from these studies across pediatric, adolescent, and adult patients with POS. Methods: The study design and pooled analysis of Studies 304, 305, and 306 has been previously published (Steinhoff BJ et al. Epilepsia 2013;54:1481–9). The Core Study of Study 311 comprised 4-week Pretreatment, 23-week Treatment (11-week Titration; 12-week Maintenance), and 4-week Follow-up Periods. Patients were permitted to receive 1–3 concomitant ASDs. Efficacy assessments, in the full intent-to-treat (ITT) analysis, included median percentage reduction in seizure frequency per 28 days from Baseline, 50% responder rate, and seizure-free status. Safety assessments included the incidence of treatment-emergent adverse events (TEAEs). Results: Overall, 1480 patients aged ≥12 years with POS were enrolled in Studies 304, 305, and 306 and included in the Safety Analysis Set (mean age [standard deviation, SD]: 34–36 [12.2–14.4] years), and 1478 patients were included in the full ITT Analysis Set. One hundred and forty-nine patients aged 4 to <12 years (mean age [SD]: 8.1 [2.1] years) with POS were included in the Safety and full ITT Analysis Sets of Study 311. In patients aged ≥12 years, median percentage changes in 28-day seizure frequency from Baseline were greater with perampanel 4 mg (-23.3%), 8 mg (-28.8%), and 12 mg (-27.2%) vs placebo (-12.8%; P<0.01, each dose); and in patients aged 4 to <12 years there was a 40.1% reduction (Figure 1). The 50% responder rate during the Maintenance Period was greater with perampanel 4 mg (28.5%), 8 mg (35.3%), and 12 mg (35.0%) vs placebo (19.3%; P<0.05, each dose) in patients aged ≥12 years, and was 46.6% in patients aged 4 to <12 years. Seizure-freedom rate was greater with perampanel 4 mg (4.4%), 8 mg (3.5%), and 12 mg (4.1%) vs placebo (1.0%; P<0.05, each dose) in patients aged ≥12 years, and was 11.5% in patients aged 4 to <12 years during the Maintenance Period. The most frequent TEAEs experienced by patients aged ≥12 years and patients aged 4 to <12 years are shown in Table 1. Conclusions: These studies suggest that perampanel is efficacious and generally safe in the treatment of POS (with/without SGS) in pediatric, adolescent, and adult patients. TEAEs observed in pediatric patients were similar to those reported in adolescents and adults. Funding: Eisai Inc.