Safety and Tolerability of Adjunctive Eslicarbazepine Acetate in Pediatric Patients (Aged 4-17 Years) With Focal Seizures

Abstract

Objective: To evaluate the safety and tolerability of adjunctive eslicarbazepine acetate (ESL) in pediatric patients (aged 4-17 years) with refractory focal seizures.

Methods: Pooled safety data from patients aged 4-17 years in Study 208 (NCT01527513) and Study 305 (NCT00988156) were analyzed. Both were randomized, double-blind, placebo-controlled studies of ESL as adjunctive treatment in pediatric patients with refractory focal seizures receiving 1 or 2 antiepileptic drugs. Incidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs of special interest were evaluated.

Results: The safety population comprised 362 patients (placebo, n = 160; ESL, n = 202). The overall incidence of TEAEs was similar between the ESL (67.8%) and placebo groups (65.6%), with no clear dose-response relationship. The most frequently reported TEAEs with ESL were headache, somnolence, vomiting, and diplopia. Overall incidences of SAEs and TEAEs leading to discontinuation were higher with ESL versus placebo (9.9% vs 5.0% and 5.9% vs 2.5%, respectively). The majority of SAEs with ESL occurred in Study 305. Two deaths were reported, 1 with ESL (0.5%) due to cluster seizures (resulting in herniation of the cerebellar tonsils) and 1 with placebo (0.6%) due to asphyxia. TEAEs related to allergic reaction, hyponatremia, hypothyroidism, cytopenia, seizure exacerbation, cognitive dysfunction, psychiatric disorders, or suicide occurred infrequently (<9%).

Conclusion: Adjunctive ESL was generally well tolerated in children aged 4-17 years with focal seizures. The safety profile of ESL in children was comparable to that observed in adults.

Keywords: adolescents; antiepileptic drugs; antiseizure drugs; children; epilepsy; pediatric; refractory; seizures.

Conflict of interest statement

Declaration of Conflicting Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MM serves on the editorial boards of the Journal of Child Neurology and Vision Development and Rehabilitation; has functioned as Principal Investigator for clinical trials research contracted through the Clinical Research Center of New Jersey (CRCNJ) sponsored by the following companies: Aquestive Therapeutics, Curemark, Eisai Inc., Impax Laboratories, Neurim Pharmaceuticals, Nuvelution Pharma Inc, PhenoSolve, Sunovion Pharmaceuticals Inc, and Teva; is consultant to Philips-Electrical Geodesics contracted through The Center for Neurological and Neurodevelopmental Health (CNNH NeuroHealth); is on the scientific advisory board of NeuroNeeds; is Chief Medical Officer, owner and founder of CNNH and CRCNJ; is a board member of CNNH Management, Inc; is President and Founder of NeurAbilities, a 501(3)c public charity; and has functioned as an expert witness in various litigation and mitigation cases, contracted through CNNH NeuroHealth. JEPG reports being on an advisory council or committee for, and receiving honoraria and consulting fees from Sunovion Pharmaceuticals Inc, Eisai, Aquestive, Greenwich, UCB, and Supernus. SMW reports receiving consulting fees from Lundbeck, Sunovion Pharmaceuticals Inc, Eisai, BioMarin, and NeuroPace. PEM reports receiving honoraria from Sunovion Pharmaceuticals Inc, Greenwich, Eisai, and LivaNova. SJ has no conflicts of interest to report. TG, DC, YL, and DB report employment with Sunovion Pharmaceuticals Inc. RC and JM report employment with BIAL–Portela & Cª, SA.

Figures

Figure 1.

Study designs. (A) Study 208. aFor patients that down-titrated from 30 mg/kg/d because of intolerable AEs during the maintenance period. bFor patients who down-titrated from 20 mg/kg/d because of intolerable AEs during the titration period. (B) Study 305. aFor patients in which tolerability was considered acceptable but therapeutic response was insufficient. bFor patients who down-titrated from 20 mg/kg/d because of intolerable AEs. AE, adverse event; FU, follow-up; PSV, post-study visit; TP, tapering off; V, visit.

Figure 2.

Overall TEAE incidence during the double-blind treatment period (A) by weight subgroup, and (B) by age subgroup. ESL, eslicarbazepine acetate; TEAE, treatment-emergent adverse event.

Figure 3.

Overall incidence of (A) SAEs and (B) TEAEs leading to discontinuation during the double-blind treatment period, by age subgroup. ESL, eslicarbazepine acetate; SAE, serious adverse event; TEAE, treatment-emergent adverse event.