Abstract Details

Title Analysis of Hepatic and Hypothyroidism-related Events in Clinical Trials of Adjunctive Eslicarbazepine Acetate in Children (Aged 4–17 years) with Focal Seizures

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-025

Objective

To evaluate the occurrence of hepatic and hypothyroidism-related events in clinical trials of adjunctive eslicarbazepine acetate (ESL) for focal (partial-onset) seizures in children.

Background ESL is a once-daily, oral antiepileptic drug for focal seizures. Liver and thyroid abnormalities were uncommon in clinical trials of ESL in adults with focal seizures.

Design/Methods This post-hoc analysis evaluated safety and tolerability data pooled from two randomized, double-blind, placebo-controlled trials (BIA-2093-208 and -305) of adjunctive ESL in pediatric patients (4–17 years) with refractory focal seizures. In Study 208-Part 1, patients (6–16 years) received ESL (target dose 30 mg/kg/day) for 12 weeks. In Study 305-Part 1, patients (2–18 years) received ESL (target dose 20 mg/kg/day) for 18 weeks. Hepatic and hypothyroidism-related treatment-emergent adverse events (TEAEs) were evaluated, as well as laboratory assessments of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH).

Results The safety population included 362 subjects (ESL n = 202; placebo n = 160). Hepatic events: no subjects taking ESL met Hy’s law criteria or had persistent ALT/AST elevations. The only hepatic event that occurred in the ESL group was ALP >1.5x the age-adjusted upper limit of normal (ESL 3.0%; placebo 1.9%). Hypothyroidism: the TEAE ‘hypothyroidism’ was reported in two subjects taking ESL (1.0%) and one taking placebo (0.6%). There were no clinically significant changes between baseline and lowest/highest on-treatment values for free T3, free T4, or TSH; small changes were apparent, which were generally larger with ESL versus placebo.

Conclusions Hepatic events and hypothyroidism were rare during adjunctive treatment with ESL for focal seizures in children aged 4–17 years.

Authors/Disclosures
James W. Wheless, MD, FAAP, FACP, FAAN, FAES, FCNS, FAAN (UTHSC-Pediatric Neurology) PRESENTER	Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Azurity. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LivaNova. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for LivaNova. Dr. Wheless has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurelius.
Sanjeev V. Kothare, MD, FAAN (Cohen Children's Hospital, Northwell Health)	Dr. Kothare has nothing to disclose.
Todd Grinnell, PhD	Todd Grinnell, PhD has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc..
David Cantu, PhD (Sunovion Pharmaceuticals Inc.)	Dr. Cantu has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc..
	No disclosure on file
	No disclosure on file
Luis Magalhaes (Bial-Portela & C S.A.)	Luis Magalhaes has received personal compensation for serving as an employee of BIAL-Portela & Cª, S.A..
David E. Blum, MD	Dr. Blum has received personal compensation for serving as an employee of Neurona Therapeutics. Dr. Blum has stock in Neurona Therapeutics.

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