Abstracts

Rationale: Perampanel (PER), a selective, noncompetitive AMPA receptor antagonist, is approved in >40 countries for adjunctive treatment of partial seizures, with or without secondarily generalized seizures, in patients with epilepsy aged ≥12yrs. Study 232 is an open-label pilot study evaluating pharmacokinetics and preliminary safety, tolerability, and efficacy data of PER oral suspension in pediatric subjects (2–˂12yrs) with epilepsy. This analysis reports the preliminary safety and efficacy results of PER as an antiepileptic drug (AED) in this study.Methods: Subjects enrolled in this Phase II study were receiving 1–3 concomitant AEDs. After up to 6 wks (up to 2-wk prospective, 4-wk retroactive) baseline, subjects received PER oral suspension once daily (7-wk titration, 4-wk maintenance) at a set daily dose of 0.015mg/kg uptitrated weekly to 0.18mg/kg or until the maximum tolerated dose was reached, with a 4-wk follow-up for subjects not entering the open-label extension. Safety endpoints included treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and TEAEs leading to discontinuation. Efficacy endpoints included median percent change in 28-day seizure frequency in the treatment phase (titration+maintenance) vs baseline (based on seizure diaries), responder rate (subjects who experienced ≥50% reduction in seizure frequency relative to baseline in the maintenance-LOCF), and seizure-free status during maintenance.Results: The treated population consisted of 50 subjects (≥2–<7yrs, N=22; ≥7–<12yrs, N=28), with mean age of 7.1yrs; 16 (32.0%) were female. Incidence of TEAEs was similar between age groups (Table 1). These TEAEs are consistent with commonly observed illnesses in this age population and TEAEs observed on PER treatment in adults and adolescents. The majority of TEAEs in both age groups were considered mild or moderate. SAEs were similar between age groups: ≥2–<7yrs=3 subjects (13.6%); ≥7–<12yrs=5 subjects (17.9%). TEAEs resulting in discontinuation occurred in 1 (4.5%) subject ≥2–<7yrs and 2 (7.1%) subjects ≥7–<12yrs. Preliminary efficacy results from this pilot study showed seizure frequency/28 days decreased for all seizure types (overall: –43.6% in ≥2–<7yrs and –33.9% in ≥7–<12yrs; overall partial: –82.5% in ≥2–<7yrs and –46.8% in ≥7–<12yrs; unclassified: –73.7% in ≥2–<7yrs and –67.3% in ≥7–<12yrs), with the exception of overall generalized seizures (–53.1% in ≥2–<7yrs and 305.4% in ≥7–<12yrs) (Fig.1). Responder rates were as follows: overall seizures: 72.7% in ≥2–<7yrs and 53.8% in ≥7–<12yrs; overall partial seizures: 82.4% in ≥2–<7yrs and 60.9% in ≥7–<12yrs; overall generalized seizures: 76.9% in ≥2–<7yrs and 33.3% in ≥7–<12yrs; unclassified seizures: 66.7% in ≥2–<7yrs and 100% ≥7–<12yrs. Seizure-free status was achieved by 9 (21.4%) subjects.Conclusions: Conclusions: Preliminary findings from the pilot Study 232 suggest that adjunctive therapy with PER oral suspension at daily doses up to 0.18mg/kg was well tolerated and might be efficacious in controlling seizures in pediatric subjects ages 2–˂12yrs with epilepsy. Support: Eisai Inc