Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily, oral antiepileptic drug (AED) for partial-onset (focal) seizures (POS). ESL is not currently FDA-approved for use in children. It is important to understand the feasibility of combining AEDs in children, as certain combinations may have different tolerability profiles relative to others. The current exploratory analysis evaluates whether taking adjunctive ESL in combination with other AEDs affects the incidence of treatment-emergent adverse events (TEAEs) in children. Methods: A subset of data (ages 4–17 years) pooled from 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 once-daily adjunctive ESL in children with POS refractory to 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. TEAE incidences were calculated. Results: The safety population (patients aged 4–17 years who received =1 dose of study drug) comprised 362 patients (placebo, n = 160; ESL, n = 202). The average (mean [SD]) number of AEDs used at baseline was 1.8 (0.52) for placebo, and 1.8 (0.56) for ESL. The most frequently used baseline AEDs were valproic acid (VPA) (placebo, 52.5%; ESL, 49.0%), carbamazepine (CBZ) (placebo, 26.3%; ESL, 30.2%), lamotrigine (LTG) (placebo, 28.1%; ESL, 24.8%), topiramate (TPM) (placebo, 24.4%; ESL, 24.8%) and levetiracetam (LEV) (placebo, 18.1%; ESL, 19.3%). Overall incidences of TEAEs according to baseline AED use are reported in Table 1. The overall placebo-adjusted incidence of TEAEs was =10% higher +VPA versus -VPA, and =10% lower +TPM versus -TPM. All other overall placebo-adjusted incidences were < 10% different between the +AED and -AED groups. Placebo-adjusted incidences of the most frequently reported TEAEs according to baseline AED use are reported in Table 2. Placebo-adjusted incidences of headache, pyrexia and partial seizures were =10% lower +LEV versus -LEV, and placebo-adjusted incidences of headache, somnolence and nasopharyngitis were =10% lower +LTG versus -LTG. Differences in some overall and individual TEAE incidences between the +AED and -AED groups may relate to differences in placebo incidences between groups (most notably in the +/-LEV, TPM and VPA groups). Conclusions: In Phase III clinical trials of ESL in children, placebo-adjusted TEAE incidences were comparable, regardless of CBZ use. However, placebo-adjusted incidences of some TEAEs were lower in patients who were taking baseline LEV, LTG and TPM and higher in those who were taking VPA, compared with patients who were not taking these AEDs at baseline. Funding: Studies sponsored by BIAL; analyses sponsored by Sunovion Pharmaceuticals Inc.