Exposure–Response Analysis of Eslicarbazepine Acetate as Adjunctive Treatment of Patients With Partial-onset Seizures

Authors: Kharidia J, Passarell JA, Maier G, Zummo J, Ludwig E, Grasela TH, Fiedler-Kelly J
Conference: ASCPT
Keywords: AED, antiepileptic, Cav-ss, central nervous system agents, dose, dosing, EC50, Emax, epilepsy, esli, logit, neurology, placebo, responder rate
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • Eslicarbazepine acetate (ESL) is a novel once-daily (QD) antiepileptic drug (AED) currently under clinical
    development in the US.
  • ESL is rapidly and extensively metabolized to its major active metabolite, eslicarbazepine, which blocks voltage-gated
    sodium channels.
  • In two phase 3 studies (Study -301 and -302) of patients with partial-onset seizures treated with 1 to 3 concomitant
    AEDs,2,3 ESL 800 mg and 1200 mg QD was well tolerated and more effective than placebo.2,3 Long-term safety was
    demonstrated in open-label extensions of these studies.
  • Examination of exposure-response relationships using efficacy endpoint data from these clinical trials, in conjunction
    with drug exposure measures generated from a previously developed population pharmacokinetic (PK) model,
    supported dose selection for ESL in the treatment of partial-onset seizures.
  • Drug exposure measures were generated from a population PK model developed previously using the
    eslicarbazepine analyte concentrations.

American Society for Clinical Pharmacology and Therapeutics (ASCPT), Dallas, Texas, March 2011

Also presented at, American College of Clinical Pharmacy (ACCP), Pittsburgh, Pennsylvania, October 2011

By Jahnavi Kharidia; Julie Passarell; Gary Maier, Jacqueline Zummo; Elizabeth Ludwig, Thaddeus H. Grasela, Jill Fiedler-Kelly