Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2020 Oct;61(10):2129-2141.
doi: 10.1111/epi.16666. Epub 2020 Sep 17.

Long-term efficacy and safety of eslicarbazepine acetate monotherapy for adults with newly diagnosed focal epilepsy: An open-label extension study

Eugen Trinka  1   2 , Rodrigo Rocamora  3   4   5 , João Chaves  6 , Joana Moreira  7 , Fábio Ikedo  7 , Patrício Soares-da-Silva  7   8   9 ; BIA-2093-311/EXT Investigators Study Group
Collaborators, Affiliations
Clinical Trial

Long-term efficacy and safety of eslicarbazepine acetate monotherapy for adults with newly diagnosed focal epilepsy: An open-label extension study

Eugen Trinka et al. Epilepsia. 2020 Oct.

Abstract

Objective: To assess the efficacy, safety, and tolerability of eslicarbazepine acetate (ESL) monotherapy during long-term treatment.

Methods: An open-label extension (OLE) study was conducted in adults completing a phase 3, randomized, double-blind, noninferiority trial, during which they had received monotherapy with either once-daily ESL or twice-daily controlled-release carbamazepine (CBZ-CR) for newly diagnosed focal epilepsy. In the OLE study, all patients received ESL (800-1600 mg/d) for 2 years. Primary efficacy outcome was retention time (from baseline of the OLE study). Secondary efficacy assessments included seizure freedom rate (no seizures during the OLE study) and responder rate (≥50% seizure frequency reduction from baseline of double-blind trial). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs).

Results: Of 206 randomized patients, 96 who received ESL in the double-blind trial (ESL/ESL) and 88 who received CBZ-CR in the double-blind trial (CBZ-CR/ESL) were treated with ESL monotherapy (89.3% overall). Treatment retention time was similar between groups, with low probability of ESL withdrawal overall (<0.07 at any time). After 24 months, the probability of ESL withdrawal was 0.0638 (95% confidence interval [CI] = 0.0292-0.1366) in the ESL/ESL group and 0.0472 (95% CI = 0.0180-0.1210) in the CBZ-CR/ESL group. Seizure freedom rates were 90.6% (ESL/ESL) and 80.7% (CBZ-CR/ESL; P = .0531). Responder rates remained >80% in both groups throughout the study. Incidence of serious TEAEs was similar between groups (7.3% vs 5.7%; 0% vs 1.1% possibly related), as were the incidences of TEAEs considered at least possibly related to treatment (17.7% vs 18.2%) and TEAEs leading to discontinuation (3.1% vs 4.5%). The types of TEAEs were generally consistent with the known safety profile of ESL.

Significance: ESL monotherapy was efficacious and generally well tolerated over the long term, including in patients who transitioned from CBZ-CR monotherapy. No new safety concerns emerged.

Keywords: antiseizure medication; carbamazepine; focal seizures; responder rate; retention; seizure freedom rate.

PubMed Disclaimer

Conflict of interest statement

E.T. reports personal fees from EVER Pharma, Marinus, Argenix, Medtronic, Bial‐Portela & Cª, S.A., NewBridge, GL Pharma, GlaxoSmithKline, Boehringer Ingelheim, LivaNova, Eisai, UCB, Biogen, Genzyme Sanofi, and Actavis; his institution received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union, FWF Osterreichischer Fond zur Wissenschaftsforderung, Bundesministerium für Wissenschaft und Forschung, and Jubilaumsfond der Österreichischen Nationalbank outside the submitted work. R.R. is a consultant for Eisai, Bial, UCB, GlaxoSmithKline and Shire, and receives grant and research support from Bial, Eisai, and UCB. J.C. has received speaker's honoraria and/or consultancy fees from Bial and Eisai and was granted with a Tecnifar Bursary. J.M., F.I., and P.S.d.S. are current employees of Bial‐Portela & Cª, S.A. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

FIGURE 1
FIGURE 1
Study design. *If seizures occurred during the evaluation period of the double‐blind (DB) study, patients were assigned to the next dose level using 1‐week titration period (controlled‐release carbamazepine [CBZ‐CR] required titration, eslicarbazepine acetate [ESL] did not) and 1‐week stabilization period, followed by 26‐week evaluation period as before. †Patients who remained seizure‐free for 26 weeks at any dose during the evaluation period entered the 26‐week maintenance period. After the 26‐week maintenance period, patients continued in an extension phase until the database lock (the database was locked after the last patient had completed the 26‐week maintenance period). For all patients participating in the open‐label extension (OLE) extension study, the last extension phase visit of the DB study was also OLE visit 1 for the OLE study. Patients who received CBZ‐CR during the DB phase 3 trial transitioned to ESL at the start of the open‐label extension study. BID, twice daily; QD, once daily. Adapted from Trinka et al 3
FIGURE 2
FIGURE 2
Patient disposition. AE, adverse event; ASM, antiseizure medication; CBZ‐CR, controlled‐release carbamazepine; ESL, eslicarbazepine acetate; FAS, Full Analysis Set
FIGURE 3
FIGURE 3
Kaplan‐Meier plots of (A) treatment retention time, (B) time to withdrawal, and (C) time to first seizure (Monotherapy Full Analysis Set). CBZ‐CR, controlled‐release carbamazepine; ESL, eslicarbazepine acetate
See this image and copyright information in PMC

References

    1. BIAL‐Portela & Cª . Zebinix®. Summary of product characteristics. 2019. Available at: https://www.ema.europa.eu/en/documents/product‐information/zebinix‐epar‐.... Accessed July 27, 2020.
    1. Sunovion Pharmaceuticals. Aptiom®. Highlights of prescribing information. 2019. Available at: http://www.aptiom.com/Aptiom‐Prescribing‐Information.pdf. Accessed July 27, 2020.
    1. Trinka E, Ben‐Menachem E, Kowacs PA, et al. Efficacy and safety of eslicarbazepine acetate versus controlled‐release carbamazepine monotherapy in newly diagnosed epilepsy: a phase III double‐blind, randomized, parallel‐group, multicenter study. Epilepsia. 2018;59(2):479–91. - PubMed
    1. Sperling MR, Harvey J, Grinnell T, Cheng H, Blum D. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial‐onset seizures: a randomized historical‐control phase III study based in North America. Epilepsia. 2015;56(4):546–55. - PMC - PubMed
    1. Jacobson MP, Pazdera L, Bhatia P, Grinnell T, Cheng H, Blum D. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial‐onset seizures: a historical‐control phase III study. BMC Neurol. 2015;15:46. - PMC - PubMed

Publication types