Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: A randomized, double-blind, placebo-controlled, parallel-group phase III study

Christian Elger, P. Halász, Joana Maia, Luis Almeida, Patrício Soares-Da-Silva

Research output: Contribution to journalArticle

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Abstract

Purpose: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1-2 antiepileptic drugs (AEDs). Methods: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n = 102) or once-daily ESL 400 mg (n = 100), 800 mg (n = 98), or 1,200 mg (n = 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). Results: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p = 0.0003) and 800-mg (p = 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56-62% of patients), lamotrigine (25-27%), and valproic acid (22-28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. Discussion: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.

Original languageEnglish
Pages (from-to)454-463
Number of pages10
JournalEpilepsia
Volume50
Issue number3
DOIs
Publication statusPublished - Mar 2009

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Seizures
Placebos
Safety
Anticonvulsants
Carbamazepine
Therapeutics
Diplopia
Partial Epilepsy
Valproic Acid
Dizziness
eslicarbazepine acetate
Headache
Maintenance

Keywords

  • Adjunctive therapy
  • Adults
  • Antiepileptic drugs
  • Eslicarbazepine acetate
  • Partial seizures
  • Refractory epilepsy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures : A randomized, double-blind, placebo-controlled, parallel-group phase III study. / Elger, Christian; Halász, P.; Maia, Joana; Almeida, Luis; Soares-Da-Silva, Patrício.

In: Epilepsia, Vol. 50, No. 3, 03.2009, p. 454-463.

Research output: Contribution to journalArticle

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abstract = "Purpose: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1-2 antiepileptic drugs (AEDs). Methods: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n = 102) or once-daily ESL 400 mg (n = 100), 800 mg (n = 98), or 1,200 mg (n = 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). Results: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p = 0.0003) and 800-mg (p = 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20{\%} (placebo), 23{\%} (400 mg), 34{\%} (800 mg), and 43{\%} (1,200 mg). Median relative reduction in seizure frequency was 16{\%} (placebo), 26{\%} (400 mg), 36{\%} (800 mg), and 45{\%} (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56-62{\%} of patients), lamotrigine (25-27{\%}), and valproic acid (22-28{\%}). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9{\%} (placebo), 4{\%} (400 mg), 8.2{\%} (800 mg), and 19.6{\%} (1,200 mg). AEs in >10{\%} of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. Discussion: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.",
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AU - Halász, P.

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AU - Almeida, Luis

AU - Soares-Da-Silva, Patrício

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N2 - Purpose: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1-2 antiepileptic drugs (AEDs). Methods: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n = 102) or once-daily ESL 400 mg (n = 100), 800 mg (n = 98), or 1,200 mg (n = 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). Results: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p = 0.0003) and 800-mg (p = 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56-62% of patients), lamotrigine (25-27%), and valproic acid (22-28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. Discussion: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.

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KW - Refractory epilepsy

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