Analysis of Sodium Levels and Hyponatremia Events in Trials of Eslicarbazepine Acetate (ESL) in Pediatric Patients (Aged 4–17 years) (P5.268)

Objective: To evaluate the effect of ESL on plasma sodium levels and hyponatremia treatment-emergent adverse events (TEAEs) in children aged 4–17 years with partial-onset (focal) seizures (POS). Background: ESL is a once-daily oral antiepileptic drug (AED) for POS. Reductions in sodium levels and clinically significant hyponatremia have previously been reported in adults taking ESL. Design/Methods: This post-hoc analysis evaluated safety and tolerability data pooled from two randomized, double-blind, placebo-controlled trials (2093–208 and -305) of adjunctive ESL in pediatric patients (4–17 years) with POS refractory to treatment with 1–2 AEDs. 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 (2–17 years) received ESL (target dose 20 mg/kg/day) for 18 weeks. All patients could continue into uncontrolled, open-label extension (OLE) studies of ESL. Plasma sodium levels and TEAEs were assessed. Results: The safety populations (4–17 years of age; ≥1 dose of study drug) of the pooled controlled studies, 1-year OLEs, and post–1-year OLEs comprised 362 (ESL, n=202; placebo, n=160), 337, and 177 patients, respectively. Potentially clinically significant (PCS) decreases (>10 mEq/L) in plasma sodium level from baseline occurred in 1.5%, 1.5%, and 0.8% of ESL patients during the controlled, 1-year OLE, and post–1-year OLE periods, respectively, and PCS (≤125 mEq/L) minimum post-dose sodium levels occurred in 0.5%, 0, and 0.8% of ESL patients, respectively. Minimum post-dose sodium levels were >135 mEq/L in >90% of patients in all periods. No hyponatremia-related TEAEs were reported during the controlled or post–1-year OLE periods. Hyponatremia was reported in one patient (0.3%) during the 1-year OLE period. Conclusions: Clinically meaningful minimum post-dose sodium levels/reductions in sodium level from baseline, and hyponatremia-related TEAEs, were infrequent in children (aged 4–17 years) taking ESL. Study Supported by: BIAL and Sunovion Pharmaceuticals Inc. Disclosure: Dr. Vaisleib has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sunovion Pharmaceuticals Inc; Greenwich Biosciences. Dr. Duchowny holds stock and/or stock options in Angel Medical Systems. Dr. Grinnell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc. Dr. Cantu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc. Dr. Vieira has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: BIAL — Portela & Ca., S.A. Dr. Ikedo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: BIAL — Portela & Ca., S.A. Dr. Li has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sunovion Pharmaceuticals Inc. Dr. Blum has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc.