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Apr 22, 2017
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Modeling and Simulation Strategy to Support Eslicarbazepine Acetate (ESL) Pediatric Dose Selection in the Treatment of Partial-Onset Seizures (POS) Based on Matching Adult Exposures

  • Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved as adjunctive treatment in adults > 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.
  • A recent Food and Drug Administration (FDA) analysis has provided evidence across anticonvulsant medications that exposure-response relationships are preserved between adult and pediatric subjects
    (>4 years) with POS.
  • The FDA specified three requirements for a submission to obtain an indication for the treatment of POS in pediatric subjects (>4 years) that rely upon extrapolation:
    • Approved indication for treatment of POS in adults
    • Pharmacokinetic (PK) analysis to determine a dosing regimen for pediatric subjects >4 years that results in exposures similar to those that are safe and effective in adults
    • A long-term open-label (OL) safety study in pediatric subjects >4 years.
  • The FDA Division of Neurology Products has determined that it is acceptable to extrapolate the efficacy and safety of drugs for both adult and pediatric populations, approved as adjunctive therapy for the treatment of POS, to their use as monotherapy, provided that efficacy and safety have been established in the respective age range.
    • FDA analysis of such drugs showed the dosages and corresponding exposures when used as monotherapy are within the ranges of dosages and corresponding exposures when used as adjunctive therapy.
  • Here we describe the application of adult exposure matching for pediatric dose selection in support of an application for a pediatric indication for ESL in US patients >4 years, for the treatment of POS as adjunctive therapy and monotherapy, without conducting a we/I-controlled efficacy study in pediatric subjects (>4 years).

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

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

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