Abstracts

Rationale: The third-generation antiepileptic drug (AED) eslicarbazepine acetate (ESL) is indicated to treat focal seizures (FS) in patients aged 4 years and older. The safety and efficacy of adjunctive ESL were studied in a double-blind, randomized, Phase 3 clinical trial (ClinicalTrials.gov NCT00988156) in pediatric (age 2-18 years) patients with FS. This post hoc analysis examined change in seizure severity between ESL and placebo. Methods: 256 pediatric patients with FS were randomized to placebo or ESL 10, 20, or 30 mg/kg/day and stratified by age group (2-6 years, 7-11 years, 12-18 years). Study periods included 8-week baseline, 6-week titration, 12-week maintenance, tapering-off, 4-week observational follow-up, and open-label extension. Seizure severity was measured with the Hague Seizure Severity Scale (HASS) at all study visits with a recall period dating to the previous visit. A longitudinal repeated measures model assessed change in HASS from baseline through 12-week maintenance. A negative change in HASS score indicates reduction in seizure severity. Fixed effects in the model included baseline HASS score, age group, treatment arm, and visit. Sensitivity analyses were conducted adjusting for ESL dose per visit. Results: 256 patients were included in the analysis (mean age 9.7): 127 in the placebo arm (mean age 9.6) and 129 in the ESL arm (mean age 9.9). Baseline AED use was comparable between the ESL and placebo groups: 16.3% (ESL) and 18.9% (placebo) used 1 AED; 73.6% and 74.0%, respectively, used 2 AEDs, and 10.1% and 7.1%, respectively used >=3. Mean time since onset of epilepsy was also similar (ESL: 6.7 years, placebo: 6.5 years). During the 18-week double-blind treatment period, statistically significant changes in the HASS total score from baseline were seen in both the ESL (-2.16, 95% confidence interval [CI]: -2.80, -1.51; P<0.0001) and placebo (-1.01, 95% CI: -1.64, -0.37; P=0.0002) arms; however, HASS total score change from baseline was significantly larger in the ESL arm compared to placebo (difference [ESL minus placebo]: -1.15 [95% CI: -2.04, -0.26]; P=0.0118) (see Figure). Similar statistically significant results were observed in the HASS total score change from baseline for each arm after adjusting for ESL dose level: placebo (-1.29, 95% CI: -2.03, -0.55; P=0.0007), ESL (-2.33, 95% CI: -3.10, -1.56; P<0.0001). The change observed in ESL arm was larger than that of placebo; however, the difference was not statistically significant (-1.04, 95% CI: -2.09, -0.01; P=0.0530). Conclusions: This post hoc analysis of a Phase 3 clinical trial indicates that adjunctive ESL in pediatric patients aged 2-18 years with FS was significantly associated with reduced seizure severity as measured by the HASS during the double-blind treatment period compared to placebo. Funding: Study funding provided by Sunovion Pharmaceuticals Inc.