An Analysis of the Efficacy and Tolerability of Eslicarbazepine Acetate (ESL) by Study Period in Two Phase III Conversion-to-ESL Monotherapy Trials (P5.276)

Objective: To examine whether seizure frequency and tolerability differ between study periods in conversion-to-ESL monotherapy trials. Background: Treatment-emergent adverse events (TEAEs) may occur more frequently with adjunctive antiepileptic drug (AED) therapy versus monotherapy, and optimal seizure control is expected at recommended maintenance doses. ESL is a once-daily oral AED for partial-onset (focal) seizures (POS). Design/Methods: Studies 093–045 and −046 were Phase III randomized, dose-blind, conversion-to-ESL monotherapy trials in adults (16–70 years) with POS uncontrolled by 1–2 AEDs. Patients were randomized 2:1 to ESL 1600 mg or 1200 mg once daily (2 weeks titration, 6 weeks baseline AED-taper, 10 weeks monotherapy). Change in standardized seizure frequency (seizures per 28 days) from baseline (ΔSSFb), responder rates (proportion of patients with ≥50% reduction in SSF), and TEAE incidences were calculated. Subjects were required to exit the study if SSF doubled from baseline. Results: Efficacy population: ESL 1600 mg, n=218; 1200 mg, n=114. Intent-to-treat (safety) population: ESL 1600 mg, n=242; 1200 mg, n=123. Efficacy outcomes were similar across treatment periods with ESL 1600 mg (ΔSSFb: −41.8 to −46.3%; responder rates: 42.5–46.7%), but with ESL 1200 mg, were greater during the monotherapy period (−47.1%; 46.2%) versus the titration (−27.5%; 38.6%) and baseline AED-taper (−37.2%; 36.0%) periods. Overall TEAE incidence (ESL 1600 mg, 57.3–60.7%; 1200 mg, 50.0–55.9%) and incidence of headache (ESL 1600 mg, 11.6–13.2%; 1200 mg, 6.5–10.8%) were comparable across treatment periods. Dizziness was less frequent in the monotherapy (ESL 1600 mg, 5.5%; ESL 1200 mg, 2.2%) versus the titration (14.5%; 14.6%) and baseline AED-taper (11.0%; 7.0%) periods. With ESL 1600 mg (but not 1200 mg), incidence of TEAEs leading to discontinuation was lowest in the monotherapy period (1600 mg: titration, 7.9%; baseline AED-taper, 4.1%; monotherapy, 2.9%; 1200 mg: 1.6–3.3%). Conclusions: ESL was effective and well tolerated during the monotherapy period of Phase III conversion-to-ESL monotherapy trials, with some differences in seizure reduction and TEAE incidences between treatment periods. Study Supported by: Sunovion Pharmaceuticals Inc. Disclosure: Dr. Chung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Chung has served as a consultant and speaker for Eisai Co., Ltd., Lundbeck LLC, Supernus Pharmaceuticals, UCB, and Upsher-Smith Laboratories. Dr. Chung has received research support from Dr. Chung has received research support from Eisai Co., Ltd., UCB Pharma, Lundbeck LLC, Upsher-Smith Laboratories, and SK Life Science, Inc. Dr. Arain has nothing to disclose. Dr. Grinnell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc. Dr. Cantu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc. Dr. Cheng has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc. Dr. Blum has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment: Sunovion Pharmaceuticals Inc.