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(Abst. 3.276), 2017

Safety and Tolerability of Adjunctive Eslicarbazepine Acetate in Pediatric Patients (aged 4–17 years) with Partial-Onset (Focal) Seizures
Authors: Mark Mintz, The Center for Neurological and Neurodevelopmental Health (CNNH); The Clinical Research Center of New Jersey (CRCNJ); Jesus E. Pina-Garza, Centennial Children's Hospital; Tristar Children's Specialists; Steven M. Wolf, Mount Sinai School of Medicine; Patricia E. McGoldrick, Mount Sinai School of Medicine; Todd Grinnell, Sunovion Pharmaceuticals Inc.; David Cantu, Sunovion Pharmaceuticals Inc.; Raquel Costa, BIAL - Portela & Cª., S.A.; Joana Moreira, BIAL - Portela & Cª., S.A.; Yan Li, Sunovion Pharmaceuticals Inc.; Sergiusz Jozwiak, Medical University of Warsaw; and David E. Blum, Sunovion Pharmaceuticals Inc.
Content: Rationale: Eslicarbazepine acetate (ESL) is a once-daily (QD) oral anti-epileptic drug (AED) for partial-onset (focal) seizures (POS). The onset and subsequent diagnosis of epilepsy is common during childhood; however, ESL is not currently FDA-approved for use in pediatric patients. Here we report an analysis of safety and tolerability data pooled from two trials of adjunctive ESL in pediatric patients with POS. Methods: Pooled safety data from patients (4-17 years) in studies 2093-208 and -305 were analyzed to address specific FDA requests for pediatric registration in the US. Both trials were randomized, double-blind, placebo-controlled studies of adjunctive ESL in pediatric patients with POS refractory to treatment with 1–2 AEDs. Study 208-Part 1 was a 12-week, Phase II study in patients aged 6–16 years, with a target ESL dose of 30 mg/kg/day. Study 305-Part 1 was an 18-week, Phase III study in patients aged 2–17 years, with a target ESL dose of 20 mg/kg/day. Incidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and TEAEs leading to discontinuation were evaluated. Results: The safety population (patients 4–17 years who received =1 dose of study drug) comprised 362 patients (placebo, n = 160; ESL, n = 202). The overall incidence of TEAEs was similar between the ESL (67.8%) and placebo group (65.6%) (Table 1); the greatest difference between treatment groups occurred in the 11–21 kg patient subgroup (ESL, 82.6%; placebo, 69.2%). The most frequently reported TEAEs with ESL (more frequent than placebo and presumed related to ESL treatment) included headache, somnolence, and vomiting (Table 1). The most frequently reported SAEs are shown in Table 2; overall SAE incidence was higher with ESL (9.9%) than placebo (5.0%). The overall incidence of TEAEs leading to discontinuation was higher with ESL (5.9%) versus placebo (2.5%); however, the incidence of each individual TEAE was =1.0%. The most frequently reported TEAEs leading to discontinuation were allergic dermatitis and edema (Table 2). Two deaths were reported, one in the ESL group (0.5%) due to cluster seizures (resulting in herniation of the cerebellar tonsils), and one in the placebo group (0.6%) due to asphyxia. Allergic reaction TEAEs were higher in the ESL (5.0%) versus placebo (1.3%) group, with no cases of Stevens–Johnson syndrome or toxic epidermal necrolysis. The SAE of 'drug reaction with eosinophilia and systemic symptoms' occurred in one patient in the ESL group (0.5%), and in no patients in the placebo group. Hypothyroidism was infrequent in both groups (ESL, 1.0%; placebo, 0.6%). No TEAEs of hyponatremia were reported; one patient taking ESL had a post-dose sodium measurement =125 mEq/L. Conclusions: Overall, treatment with ESL was generally well tolerated in pediatric patients (4–17 years) with POS. The safety profile of ESL in pediatric patients is comparable to that previously reported for adult patients with POS. Funding: Studies sponsored by BIAL; analyses sponsored by Sunovion Pharmaceuticals Inc.
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