Physiologically Based and Population Pharmacokinetic (PBPK, PPK) Modeling and Simulation to Support Dose Selection and Study Design for Eslicarbazepine Acetate (ESL) Adjunctive Therapy in Infants with Partial-Onset Seizures (POS)

Authors: Sunkaraneni S, Bihorel S, Ludwig EA, Fiedler-Kelly J, Morris D, Hopkins SC, Galluppi G, Blum D
Conference: American Academy of Neurology (AAN)
Keywords: AED, dose selection, epilepsy, eslicarbazepine, neurology, PBPK, Pediatric, population pharmacokinetic, PPK
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

  • Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved as adjunctive treatment in adults ≥18 years for partial-onset seizures (POS) in the USA and Canada, and as monotherapy for POS in the USA. In Europe, ESL is approved as adjunctive therapy in adults, adolescents, and children aged above 6 years, with POS with or without secondary generalization.
  • The safety and efficacy of ESL as adjunctive treatment has been studied in pediatric populations and is supported for subjects ≥4 years by population pharmacokinetic (PPK) models of the plasma concentration of eslicarbazepine, the primary ESL metabolite.1
  • A modeling and simulation strategy with sequential PPK extrapolation (‘top down’ approach) and physiologically based pharmacokinetic (PBPK) prediction (‘bottom up’ approach) was employed, using data from pediatric patients and adults, in order to inform dose selection and design of a clinical trial (Study SEP093-363) in infant and pediatric patients aged 1 month–<4 years with POS.

69th American Academy of Neurology Annual Meeting, April 22–28 2017, Boston, MA, USA

Soujanya Sunkaraneni, Sebastien Bihorel, Elizabeth A Ludwig, Jill Fiedler-Kelly, Denise Morris, Seth Hopkins, Gerald Galluppi, David Blum