To explore perampanel exposure–response relationships for cognition and safety in pediatric patients (aged 4 to <12 years) with partial-onset seizures (POS) or primary generalized tonic-clonic seizures (PGTCS) using pharmacokinetic/pharmacodynamic (PK/PD) analyses.

Perampanel is a once-daily oral anti-seizure medication for POS and PGTCS.

Data from POS and PGTCS subjects were pooled from an open-label, Phase III study of adjunctive perampanel oral suspension (NCT02849626). Graphical PK/PD analyses assessed potential relationships between: (1) model-predicted average perampanel concentration at steady state (C_av,ss) and cognitive endpoints (change from baseline in A-B Neuropsychological Assessment [ABNAS], Child Behavior Checklist [CBCL], and Lafayette Grooved Pegboard Test [LGPT]); (2) perampanel C_av,ss  and the most frequent (occurring in ≥10 subjects) treatment-emergent adverse events (TEAEs); (3) model-predicted maximum perampanel concentration at steady state (C_max,ss) and the most frequent TEAEs. If a relationship was apparent, PK/PD modeling using binary logistic regression was performed.

These assessments suggest there is no exposure–response relationship between perampanel and cognitive or safety outcomes in pediatric patients with POS or PGTCS, supporting the conclusion that cognitive function is not clinically impaired by perampanel administration.

Funding: Eisai Inc.