Efficacy and safety of eslicarbazepine acetate versus controlled-release carbamazepine monotherapy in newly diagnosed epilepsy: A phase III double-blind, randomized, parallel-group, multicenter study

Epilepsia. 2018 Feb;59(2):479-491. doi: 10.1111/epi.13993. Epub 2018 Jan 25.


Objective: We assessed the efficacy and safety of once-daily eslicarbazepine acetate in comparison with twice-daily (BID) controlled-release carbamazepine (carbamazepine-CR) monotherapy in newly diagnosed focal epilepsy patients.

Methods: This randomized, double-blind, noninferiority trial (NCT01162460) utilized a stepwise design with 3 dose levels. Patients who remained seizure-free for the 26-week evaluation period (level A: eslicarbazepine acetate 800 mg/carbamazepine-CR 200 mg BID) entered a 6-month maintenance period. If a seizure occurred during the evaluation period, patients were titrated to the next target level (level B: eslicarbazepine acetate 1200 mg/carbamazepine-CR 400 mg BID, level C: eslicarbazepine acetate 1600 mg/carbamazepine-CR 600 mg BID) and the evaluation period began again. The primary endpoint was the proportion of seizure-free patients for 6 months after stabilization in the per protocol set. The predefined noninferiority criteria were -12% absolute and -20% relative difference between treatment groups.

Results: Eight hundred fifteen patients were randomly assigned; 785 (388 in the eslicarbazepine acetate group and 397 in the carbamazepine-CR group) were included in the per protocol set, and 813 (401 in the eslicarbazepine acetate group and 412 in the carbamazepine-CR group) were included in the full analysis set for the primary analysis. Overall, 71.1% of eslicarbazepine acetate-treated patients and 75.6% of carbamazepine-CR-treated patients were seizure-free for ≥6 months at the last evaluated dose (average risk difference = -4.28%, 95% confidence interval [CI] = -10.30 to 1.74; relative risk difference = -5.87%, 95% CI = -13.50 to 2.44) in the per protocol set. Rates of treatment-emergent adverse events were similar between groups for patients in the safety set. Noninferiority was also demonstrated in the full analysis set, as 70.8% of patients with eslicarbazepine acetate and 74.0% with carbamazepine-CR were seizure-free at the last evaluated dose (average risk difference = -3.07, 95% CI = -9.04 to 2.89).

Significance: Treatment with eslicarbazepine acetate was noninferior to BID carbamazepine-CR. With its once-daily formulation, eslicarbazepine acetate provides a useful option for first-line monotherapy for adults with newly diagnosed epilepsy and focal onset seizures.

Keywords: carbamazepine; eslicarbazepine acetate; focal onset seizures; monotherapy; newly diagnosed.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / therapeutic use
  • Carbamazepine / administration & dosage*
  • Carbamazepine / therapeutic use
  • Delayed-Action Preparations
  • Dibenzazepines / administration & dosage*
  • Dibenzazepines / therapeutic use
  • Dizziness / chemically induced
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Epilepsies, Partial / drug therapy*
  • Equivalence Trials as Topic
  • Fatigue / chemically induced
  • Female
  • Headache / chemically induced
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Treatment Outcome
  • Voltage-Gated Sodium Channel Blockers / administration & dosage*
  • Voltage-Gated Sodium Channel Blockers / therapeutic use
  • Young Adult
  • gamma-Glutamyltransferase / blood


  • Anticonvulsants
  • Delayed-Action Preparations
  • Dibenzazepines
  • Voltage-Gated Sodium Channel Blockers
  • Carbamazepine
  • eslicarbazepine acetate
  • gamma-Glutamyltransferase
  • Alanine Transaminase