title: Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sperling
authors.forename: Bassel
authors.initials: B
authors.lastname: Abou-Khalil
authors.forename: Jay
authors.initials: J
authors.lastname: Harvey
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Rogin
authors.forename: Arnaud
authors.initials: A
authors.lastname: Biraben
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Galimberti
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Kowacs
authors.forename: Seung Bong
authors.initials: SB
authors.lastname: Hong
authors.forename: Hailong
authors.initials: H
authors.lastname: Cheng
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.forename: Teresa
authors.initials: T
authors.lastname: Nunes
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D003984:Dibenzazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012640:Seizures / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; C416835:eslicarbazepine acetate
keywords: Adjunctive therapy; Antiepileptic drugs; Eslicarbazepine acetate; North America; Partial-onset seizures; Refractory epilepsy