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

Research output: Contribution to journalArticle

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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
Pages (from-to)244-253
Number of pages10
JournalEpilepsia
Volume56
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

Fingerprint

Seizures
Randomized Controlled Trials
Placebos
Therapeutics
eslicarbazepine acetate
Maintenance
Diplopia
Dizziness
Anticonvulsants
Nausea
Canada
Headache
Safety
Incidence

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures : Results of a phase III, double-blind, randomized, placebo-controlled trial. / Sperling, Michael R.; Abou-Khalil, Bassel; Harvey, Jay; Rogin, Joanne B.; Biraben, Arnaud; Galimberti, Carlo A.; Kowacs, Pedro A.; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares-Da-Silva, Patrício.

In: Epilepsia, Vol. 56, No. 2, 01.02.2015, p. 244-253.

Research output: Contribution to journalArticle

Sperling, MR, Abou-Khalil, B, Harvey, J, Rogin, JB, Biraben, A, Galimberti, CA, Kowacs, PA, Hong, SB, 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, vol. 56, no. 2, pp. 244-253. https://doi.org/10.1111/epi.12894
Sperling, Michael R. ; Abou-Khalil, Bassel ; Harvey, Jay ; Rogin, Joanne B. ; Biraben, Arnaud ; Galimberti, Carlo A. ; Kowacs, Pedro A. ; Hong, Seung Bong ; Cheng, Hailong ; Blum, David ; Nunes, Teresa ; Soares-Da-Silva, Patrício. / Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures : Results of a phase III, double-blind, randomized, placebo-controlled trial. In: Epilepsia. 2015 ; Vol. 56, No. 2. pp. 244-253.
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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.",
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AU - Abou-Khalil, Bassel

AU - Harvey, Jay

AU - Rogin, Joanne B.

AU - Biraben, Arnaud

AU - Galimberti, Carlo A.

AU - Kowacs, Pedro A.

AU - Hong, Seung Bong

AU - Cheng, Hailong

AU - Blum, David

AU - Nunes, Teresa

AU - Soares-Da-Silva, Patrício

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N2 - 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.

AB - 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.

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