Efficacy, Safety, and Tolerability of Adjunctive Eslicarbazepine Acetate in Focal Seizure Patients with Focal to Bilateral Tonic-clonic Seizures at Baseline
Abstract number :
2.243
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2022
Submission ID :
2204889
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
Steve Chung, MD – Banner – University Medical Center Phoenix, University of Arizona College of Medicine – Phoenix; Samy Guirguis, MD – Sunovion Pharmaceuticals Inc.; David Cantu, PhD – Sunovion Pharmaceuticals Inc.; Joana Moreira, PharmD – Bial Portela e C. SA; Luís Magalhães, MD, PhD, 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 (ESL) is approved for the treatment of partial onset (focal) seizures in patients 4 years of age and older. Focal to bilateral tonic-clonic seizures (FBTCS) are the most severe form of focal seizures and may place patients at increased risk of injuries and sudden unexpected death. Here we report the efficacy, safety, and tolerability of ESL in a subset of focal seizure patients who experienced FBTCS at baseline (BL).
Methods: Data from 3 multinational, randomized, double-blind, placebo-controlled trials of ESL in patients (N=1447) with focal seizures were pooled for this post-hoc analysis. The studies were similar in design; after an 8-week BL period, patients were randomized to placebo (PBO), ESL 400 mg, or ESL 800 mg daily. ESL doses were titrated over 2 weeks to doses of 800 mg or 1200 mg daily, which remained constant through the 12-week maintenance period. This analysis included patients with focal seizures who had ≥ 1 FBTCS during BL and who received ≥ 800 mg/day during the maintenance period. Efficacy was assessed by analysis of covariance of standardized seizure frequency (SSF, FBTCS/28 day) during the maintenance period compared with PBO, responder analysis [percentage of patients with ≥ 50%, ≥ 75%, and 100% reduction in SSF compared to BL (Cochran–Mantel–Haenszel test)], and time to first seizure (Kaplan-Meier). Adverse events (AEs) were collected at all study visits.
Results: Of the 1447 patients, a total of 438 patients, ages 16-69, met the criteria for this analysis and received > 1 dose of study medication (safety population) and 429 patients had ≥ 1 post-baseline seizure diary entry (efficacy population). BL characteristics were balanced among the 3 treatment groups. During the BL period, median FBTCS SSF was 2.5, 2.5, and 2.4 in PBO, ESL 800 mg, and ESL 1200 mg groups, respectively. During maintenance, the FBTCS SSF was less compared to PBO in both ESL groups, but only significant in the ESL 1200 mg group (PBO, 1.1; ESL 800, 0.9; ESL 1200, 0.8; P=0.0395). A greater percentage of patients treated with ESL 1200 mg achieved ≥ 50% reduction in SSF (61.9%, p=0.005) or ≥ 75% reduction in SSF (46.0%, p=0.0315) compared with PBO (≥ 50%, 45.6%; ≥ 75%, 33.3%). Time to first seizure was significantly longer in both ESL groups compared with placebo (Figure). The most frequently reported AEs were dizziness, headache, nausea, somnolence, and vomiting and the incidence of each increased with ESL dose (Table 1). AEs leading to discontinuation increased with ESL dose, with dizziness being the most common AE cited (PBO 1.3%; ESL 800 3.7%; ESL 1200 7.2%).
Conclusions: Adjunctive ESL 800 mg and 1200 mg was well-tolerated and increased the time to first seizure for patients with FBTCS. Rates of seizure reduction were consistent with those previously reported for the entire focal seizure population and ESL 1200 mg significantly improved the 50% and 75% responder rates compared to PBO. ESL may be a useful treatment option for FBTCSs.
Funding: Funded by Sunovion Pharmaceuticals, Inc., and Bial - Portela e Ca, SA.
Anti-seizure Medications