Modeling and Simulation to Support Clinical Development of Eslicarbazepine Acetate in Partial-Onset Epilepsy

Authors: Sunkaraneni S, Blum D, Fiedler-Kelly J, Passarell JA, Ludwig EA
Conference: ACCP
Keywords: AED, epilepsy, eslicarbazepine, eslicarbazepine acetate, neurology, PK, PK/PD
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) approved by the US Food and Drug Administration for the treatment of partial-onset seizures (POS) as monotherapy or adjunctive therapy. ESL is approved by the European Medicines Agency as adjunctive therapy of POS in adults.

  • In Phase III studies in patients with POS not adequately controlled by previous AED therapy, ESL has demonstrated efficacy, both as adjunctive therapy1–3 and monotherapy.4,5
  • ESL is administered orally, and is rapidly metabolized to the primary active metabolite, eslicarbazepine.6
  • A model-based drug development paradigm was employed for the ESL adjunctive therapy and monotherapy development programs, to evaluate eslicarbazepine pharmacokinetics (PK) and relationships between eslicarbazepine and efficacy and safety outcomes, and to inform decisions on dose selection.

American College of Clinical Pharmacology (ACCP) Annual Meeting, September 27-29, 2015, San Francisco, CA

By Soujanya Sunkaraneni, David Blum, Jill Fiedler-Kelly. Julie A Passarell, Elizabeth A Ludwig