Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug (ASD) 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. Here, we report a post hoc analysis of safety and efficacy data by concomitant baseline ASD use during the 311 Core Study. Methods: The Core Study 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. For this post hoc analysis, safety and efficacy were assessed by number and most common concomitant ASDs received during Baseline. Safety assessments (all seizure types combined) included monitoring of treatment-emergent adverse events (TEAEs). Efficacy assessments (split by seizure type) included median percent change in seizure frequency per 28 days from Baseline during the Treatment Period and 50% responder rates during the Core Study Maintenance Phase. Results: Overall, 180 patients were enrolled and treated. Of these, 35 (19.4%), 100 (55.6%), and 45 (25.0%) patients received 1, 2, or 3 ASDs during Baseline, respectively. The most common concomitant ASDs during Baseline were levetiracetam (32.2%), valproic acid (30.0%), clobazam (26.7%), lamotrigine (25.0%), topiramate (16.1%), and carbamazepine (14.4%); patients could receive >1 of the most common ASDs. An overview of TEAEs by concomitant ASD use is presented in Table 1. Discontinuations due to adverse events (AEs) occurred in 4 (11.4%), 7 (7.0%), and 3 (6.7%) patients with 1, 2, or 3 concomitant ASDs, respectively. For the most common baseline ASDs, discontinuations due to AEs ranged from no patients (carbamazepine) to 6 (10.3%) patients (levetiracetam). Median percent reductions in seizure frequency per 28 days are shown in Figures 1A-B. Fifty-percent responder rates for POS and PGTCS by number of baseline ASDs were: 1 ASD: 55.6% (15/27) and 80.0% (4/5); 2 ASDs: 48.8% (40/82) and 50.0% (6/12); and 3 ASDs: 35.9% (14/39) and 80.0% (4/5), respectively. For the most common concomitant ASDs these were: levetiracetam: 48.9% (22/45) and 55.6% (5/9); valproic acid: 39.6% (19/48) and 75.0% (3/4); clobazam: 52.5% (21/40) and 66.7% (4/6); lamotrigine: 42.9% (15/35) and 77.8% (7/9); topiramate: 54.5% (12/22) and 40.0% (2/5); and carbamazepine: 42.3% (11/26) and 0.0% (0/0), respectively. Conclusions: These data suggest adjunctive perampanel is generally well tolerated and efficacious in pediatric patients (aged 4 to ˂12 years) with POS (with/without SGS) or PGTCS, irrespective of baseline ASD use. Funding: Eisai Inc.