Use of Pharmacokinetic-Pharmacodynamic Modeling and Simulations to Predict Efficacy Outcomes with Eslicarbazepine Acetate 800 mg Once Daily as Monotherapy

Authors: Sunkaraneni S, Passarell JA, Pitner J, Grinnell T, Blum D
Conference: American Academy of Neurology (AAN)
Keywords: AED, eslicarbazepine, monotherapy, neurology, Phase 3, seizures
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved as adjunctive treatment for partial-onset seizures (POS) in the USA, Europe, and Canada, and as monotherapy for POS in the USA.
  • Following oral dosing, ESL is rapidly and extensively metabolized to the active metabolite, eslicarbazepine,1 which is thought to act primarily by preferentially stabilizing the inactivated state of voltage-gated sodium channels.2
  • Conversion to ESL monotherapy (1200 mg and 1600 mg QD) has been studied in two Phase III studies (093-045 and 093-046) in patients with POS whose seizures were previously not adequately controlled while taking either one or two AEDs.3–5 Conversion to ESL monotherapy at both the doses examined (1200 mg and 1600 mg) was found to be effective (superior to a historical control) and well tolerated.3–5
  • The FDA-recommended dose range for ESL maintenance is 800–1600 mg QD.6 For patients on ESL monotherapy, a maintenance dose of 800 mg QD should generally be considered for patients who are unable to tolerate a dose of 1200 mg QD.6 Here, pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to estimate the efficacy of conversion of patients to ESL monotherapy (800 mg QD; this dose was not examined as a maintenance dose in the Phase III studies). The model was also used to predict efficacy outcomes in patients converting from either one or two AEDs (approximately 70% of patients were taking one AED during the baseline period5).

American Academy of Neurology (AAN) Annual Meeting, April 15–21 2016, Vancouver, BC, Canada

By Soujanya Sunkaraneni, Julie A Passarell, Janet Pitner, Todd Grinnell, David Blum