Evaluate population PK and exposure-response relationships of adjunctive perampanel in pediatric patients (aged 2–<12 years or 4–<12 years, respectively) with partial-onset seizures (POS) or primary generalized tonic-clonic seizures (PGTCS) compared with healthy subjects and adolescent/adult patients (aged ≥12 years) with POS or PGTCS.

Assessment of the PK, safety, and efficacy of antiepileptic drugs (AEDs) in pediatric patients is necessary to identify appropriate doses for these patients. Perampanel is a once-daily oral AED for POS and PGTCS.

PK and exposure-response analyses were performed using NONMEM^® v7.3. Simulations were conducted across five age groups for perampanel 8 mg/day, with/without enzyme-inducing AEDs (EIAEDs), using pooled data from previous clinical trials in pediatric and adolescent/adult patients with POS or PGTCS, and healthy subjects. Covariates, including age and body weight, assessed between-subject variability. Exposure-response analyses were performed for POS and PGTCS separately.

PK analysis included 2265 subjects (pediatrics, n=127). Perampanel apparent clearance (CL/F) was not significantly affected by age and body weight, with/without coadministered EIAEDs; CL/F and derived actual exposure parameters were similar across age groups. Model-derived maximum concentration and area under the curve at steady state were comparable across age groups with/without EIAEDs, indicating bioequivalent exposures in pediatrics and adults when administered at the same dose. Exposure-response analysis included 1825 patients with POS (pediatrics, n=75) and 155 with PGTCS (pediatrics, n=6). For POS, the relationship between observed percent change in 28-day average seizure frequency and model-predicted perampanel average concentration at steady-state was comparable across age groups; this was also suggested for PGTCS, but pediatric patient numbers were too low (n=6) to draw conclusions.

Perampanel PK and exposure-response outcomes in pediatric patients with POS or PGTCS were similar to those in adults/adolescents, suggesting that pediatric patients could be up-titrated to the same perampanel dose as adolescents/adults to achieve efficacious exposures.

Funding: Eisai Inc.