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.

Abstract

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.

• Authors: Eugen Trinka, Elinor Ben-Menachem, Pedro A Kowacs, Christian Elger, Birgit Keller, Kurt Löffler, José Francisco Rocha, Patrício Soares-da-Silva
• Journal: Epilepsia (Epilepsia) Vol. 59 Issue 2 Pg. 479-491 (02 2018) ISSN: 1528-1167 [Electronic] United States
• PMID: 29369348 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Chemical References

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

Topics

• Adult
• Alanine Transaminase (blood)
• Anticonvulsants (administration & dosage, therapeutic use)
• Carbamazepine (administration & dosage, therapeutic use)
• Delayed-Action Preparations
• Dibenzazepines (administration & dosage, 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, therapeutic use)
• Young Adult
• gamma-Glutamyltransferase (blood)