Relationship between exposure and efficacy of eslicarbazepine acetate monotherapy

Authors: Rogin JB, Cole AJ, Strom L, Passarell JA, Fiedler-Kelly J, Ludwig EA, Blum D, Sunkaraneni S
Conference: American Epilepsy Society (AES)
Keywords: AED, epilepsy, eslicarbazepine, eslicarbazepine acetate, neurology, PK, PK/PD
Division: Cognigen

Introduction

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

  • After oral administration, ESL is rapidly hydrolyzed to eslicarbazepine (the primary active metabolite) by hydrolytic first-pass metabolism.1
  • Two multicenter, Phase III studies (093-045 and -046) demonstrated ESL monotherapy to be effective and well tolerated in patients with POS uncontrolled by 1–2 AEDs, compared with a historical control.2,3
  • In a pooled analysis of the data from studies -045 and -046, there was a difference in exit rates between the ESL 1600 mg (20.6%, 95% confidence interval [CI]: 15.6−26.8%) and ESL 1200 mg doses (30.8%, CI: 23.0−40.5%; p=0.062).4
  • In addition, higher ESL doses lead to greater eslicarbazepine exposure.5
  • This analysis examines the relationship between eslicarbazepine exposure and the efficacy of ESL monotherapy, using data from studies -045 and -046, to assess whether monitoring plasma eslicarbazepine concentrations could be useful to physicians when making decisions regarding ESL dosing.
  • ESL is not approved for monotherapy use.

Poster originally presented at: American Epilepsy Society (AES) Annual Meeting: December 5-9, 2014, Seattle, WA. Encore presented at: American College of Clinical Pharmacology (ACCP) Annual Meeting, September 27-29, 2015, San Francisco, CA

By Joanne B Rogin, Andrew J Cole, Laura Strom, Julie A Passarell, Jill Fiedler-Kelly, Elizabeth A Ludwig, David Blum, Soujanya Sunkaraneni