Efficacy, Safety, and Tolerability of Adjunctive Eslicarbazepine Acetate in Focal Seizure Patients With Focal to Bilateral Tonic-Clonic Seizures at Baseline (P14-1.003)

Abstract

<h3>Objective:</h3> Here we report the efficacy, safety, and tolerability of eslicarbazepine acetate (ESL) in patients who experienced baseline focal to bilateral tonic-clonic seizures (FBTCS). <h3>Background:</h3> ESL is approved for focal seizure treatment. FBTCS are the most severe form of focal seizures and place patients at increased risk of injuries and sudden unexpected death. <h3>Design/Methods:</h3> Pooled data from 3 randomized clinical trials of ESL in patients with focal seizures (N=1447) were analyzed. After an 8-week baseline, patients were titrated over 2 weeks to their maintenance dose (400, 800, or 1200 mg/day; 12 weeks). Efficacy was assessed in a patient subset with ≥1 baseline FBTCS and ≥800 mg/day ESL maintenance dose by comparing standardized seizure frequency (SSF, FBTCS/28 day) during the maintenance period with placebo. Adverse events (AEs) were collected and tabulated. <h3>Results:</h3> A total 438 patients, aged 16–69, met the subset criteria and 429 patients had ≥1 post-baseline seizure diary entry. Baseline characteristics were balanced among treatment groups. Baseline median FBTCS SSF was 2.5 (placebo), 2.5 (ESL 800mg), and 2.4 (ESL 1200mg). During maintenance, the FBTCS SSF was lower in ESL groups (800mg, 0.9; 1200mg, 0.8) compared to placebo (1.1), and was significant for ESL 1200mg (P=0.0395, ANCOVA). ESL 1200mg patients achieved ≥50% reduction in SSF (61.9%, P=0.005, Cochran-Mantel-Haenszel test) or ≥75% reduction in SSF (46.0%, P=0.0315) at greater rates versus placebo (≥50%, 45.6%; ≥75%, 33.3%). Time to first seizure was significantly longer in ESL groups than placebo (Kaplan-Meier). Incidence of AEs and AEs leading to discontinuation increased with ESL dose. <h3>Conclusions:</h3> Adjunctive ESL was well-tolerated and increased time to first seizure for patients with FBTCS. ESL 1200mg significantly improved 50% and 75% responder rates compared to placebo. ESL may be a useful treatment option for FBTCS. <b>Disclosure:</b> The institution of Dr. Chung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ucb pharma. Dr. Chung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SK Life sciences. Dr. Chung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for eisai. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for eisai. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for ucb. Dr. Chung has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for SK Life sciences. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for sunovion. Samy Guirguis has nothing to disclose. Dr. Cantu has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc.. Joana Moreira has received personal compensation for serving as an employee of BIAL. Luis Magalhaes has received personal compensation for serving as an employee of BIAL-Portela &amp; Cª, S.A.. Ms. Hall has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc.. Ian Zhang has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc.. Todd Grinnell, PhD has received personal compensation for serving as an employee of Sunovion Pharmaceuticals Inc..