title: 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.
abstract: OBJECTIVE
  To assess the efficacy and safety of eslicarbazepine acetate (ESL) as monotherapy in North American patients with partial-onset seizures (POS).
  
  
  METHODS
  This multicenter, randomized, double-blind "withdrawal to monotherapy" study used historical control data as the comparator. Adults with POS medically uncontrolled by one to two antiepileptic drugs gradually converted to ESL monotherapy. Following an 8-week baseline period, patients were randomized 2:1 to receive ESL 1,600 mg (n = 128) or 1,200 mg QD (n = 65) for 18 weeks. The primary end point was the proportion of patients meeting predefined exit criteria (signifying worsening seizure control). Treatment was considered effective if the 95% upper confidence limit (UCL) for the Kaplan-Meier estimated exit rate was lower than the exit rate threshold calculated from the historical control (65.3%).
  
  
  RESULTS
  Kaplan-Meier estimated exit rates were: ESL 1,600 mg, 28.7% (95% CI 21.2-38.1%) and 1,200 mg, 44.4% (32.5-58.3%). The difference between doses was not significant (p = 0.07). For both doses, the 95% UCLs for the exit rate were ˂ 65.3%; ESL monotherapy was considered superior to the historical control. There was no statistically significant increase in the risk of study exit related to carbamazepine use. Nine (7.6%) and five patients (8.3%) remained seizure-free during the 10-week monotherapy period, while taking ESL 1,600 and 1,200 mg, respectively. The reductions in median standardized seizure frequency (seizures per 28 days) between baseline and the 18-week treatment period were: ESL 1,600 mg, 42% and 1,200 mg, 31%. Treatment-emergent adverse events (TEAEs) occurring in ≥ 10% of patients were dizziness, headache, fatigue, somnolence, nausea, and nasopharyngitis. The TEAE most frequently leading to discontinuation was hyponatremia (2.1%).
  
  
  CONCLUSIONS
  ESL was efficacious and well tolerated as monotherapy in North American patients, and led to a reduction in seizure frequency. Exit rates for ESL 1,600 and 1,200 mg QD were superior to the historical control; the difference in exit rates between doses was not statistically significant.
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sperling
authors.forename: Jay
authors.initials: J
authors.lastname: Harvey
authors.forename: Todd
authors.initials: T
authors.lastname: Grinnell
authors.forename: Hailong
authors.initials: H
authors.lastname: Cheng
authors.forename: David
authors.initials: D
authors.lastname: Blum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage*; D003984:Dibenzazepines / Q000008:administration & dosage*; D004311:Double-Blind Method; D057915:Drug Substitution / Q000379:methods; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; C416835:eslicarbazepine acetate
keywords: Anticonvulsants; Antiepileptic drugs; Eslicarbazepine acetate; Monotherapy; Partial-onset seizures; Refractory epilepsy