Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial

Michael R. Sperling, Bassel Abou-Khalil, Jay Harvey, Joanne B. Rogin, Arnaud Biraben, Carlo A. Galimberti, Pedro A. Kowacs, Seung Bong Hong, Hailong Cheng, David Blum, Teresa Nunes, Patrício Soares-Da-Silva

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62 Scopus citations

Abstract

Objective To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. Methods This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1-2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Results Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. Significance Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used.

Original languageEnglish (US)
Pages (from-to)244-253
Number of pages10
JournalEpilepsia
Volume56
Issue number2
DOIs
StatePublished - Feb 1 2015

Keywords

  • Adjunctive therapy
  • Antiepileptic drugs
  • Eslicarbazepine acetate
  • North America
  • Partial-onset seizures
  • Refractory epilepsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Sperling, M. R., Abou-Khalil, B., Harvey, J., Rogin, J. B., Biraben, A., Galimberti, C. A., Kowacs, P. A., Hong, S. B., Cheng, H., Blum, D., Nunes, T., & Soares-Da-Silva, P. (2015). Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial. Epilepsia, 56(2), 244-253. https://doi.org/10.1111/epi.12894