Safety and Efficacy of Adjunctive Eslicarbazepine Acetate for Focal Seizures When Initiated at 400mg Without Concomitant Carbamazepine
Abstract number :
2.238
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2022
Submission ID :
2204792
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Mohamad Koubeissi, MD – George Washington University; Jihad Rizkallah, MD – Sunovion Pharmaceuticals Inc.; David Cantu, PhD – Sunovion Pharmaceuticals Inc.; Helena Gama, MD – Bial Portela e C. SA; Joana Moreira, PharmD – Bial Portela e C. SA; Diane Hall, BS, Statistics – Sunovion Pharmaceuticals Inc.; Yi Zhang, DrPH, Biostatistics – Sunovion Pharmaceuticals Inc.; Todd Grinnell, AB, Biochemistry – Sunovion Pharmaceuticals Inc.
Rationale: Eslicarbazepine acetate (ESL) is an antiseizure medication (ASM) approved in the U.S. and Europe for the treatment of partial-onset (focal) seizures in pediatric and adult patients. ESL and carbamazepine (CBZ) are members of the dibenzazepine carboxamide class of ASMs, which are hypothesized to exert anti-seizure effects by inhibiting voltage-gated sodium channels, and therefore ESL tolerability and efficacy may be affected by concomitant CBZ. While the use of CBZ in treating focal seizures has declined in recent years, approximately 50% of patients included in a previous analysis describing safety and efficacy of ESL for treatment of focal seizures in 3 randomized, double-blind, placebo controlled clinical trials received concomitant CBZ at baseline (Biton et al., 2017). Approximately 50% of patients also initiated ESL treatment at 800 mg/day. The objective of the present post-hoc analysis was to assess safety and tolerability of ESL under more typical current clinical circumstances, in a subset of those patients with the recommended initial dose of 400 mg/day and in the absence of concomitant CBZ (400/CBZ-).
Methods: Patients 16 to 75 years old with uncontrolled focal seizures taking stable doses of 1 to 3 ASMs not including CBZ and initiating ESL at 400 mg/day were included in this analysis from the 3 pivotal trials. Following an 8-week baseline period, adjunctive ESL was titrated over 2 weeks to the final maintenance dose (800 or 1200 mg/day for 12 weeks). Treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to discontinuation were recorded at each study visit. Efficacy was assessed by evaluating standardized seizure frequency (SSF), percentage reduction in SSF, and percentage of patients reaching 50% and 75% response rates at maintenance compared to baseline.
Results: A total of 437 (placebo, n=225; 800 mg/day, n=169; 1200 mg/day, n=43) of the original 1447 patients across the 3 trials met criteria for this analysis. Incidence of TEAEs is presented in Table 1. Overall incidence of any TEAE increased with dose but was lower in 400/CBZ- patients than observed in the overall study population. Incidence of TEAEs typically associated with sodium channel blockers (somnolence, headache, diplopia, dizziness, and nausea) were lower in 400/CBZ- patients than in the overall study population. Fewer 400/CBZ- patients discontinued due to TEAEs than the overall study population. SAE rates were higher in 400/CBZ- patients than the overall study population. SSF, percentage reduction in SSF, and percentage of patients reaching 50% and 75% seizure reduction in focal seizures were similar between 400/CBZ- patients and the overall study population.
Conclusions: Approximately 50% of patients in the initial tolerability and efficacy analysis initiated adjunctive ESL at 800 mg/day and with concomitant CBZ at baseline. This post-hoc analysis suggests increased tolerability with similar efficacy in 400/CBZ- patients, a population that better represents the current clinical usage of ESL in the U.S.
Funding: Sunovion Pharmaceuticals, Inc.
Anti-seizure Medications