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

SummaryObjective: 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 À12% absolute and À20% 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 = À4.28%, 95% confidence interval [CI] = À10.30 to 1.74; relative risk difference = À5.87%, 95% CI = À13.50 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 = À3.07, 95% CI = À9.04 to

Long‐term safety and efficacy of lacosamide and controlled‐release carbamazepine monotherapy in patients with newly diagnosed epilepsy

“…10,[12][13][14] These trials showed that levetiracetam, zonisamide, lacosamide, and eslicarbazepine were noninferior to carbamazepine-CR, and provided class I evidence of efficacy in adults with focal epilepsy that led to approval of these drugs as monotherapy options in Europe. 10,[12][13][14] These trials showed that levetiracetam, zonisamide, lacosamide, and eslicarbazepine were noninferior to carbamazepine-CR, and provided class I evidence of efficacy in adults with focal epilepsy that led to approval of these drugs as monotherapy options in Europe.…”

Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis

“…Four trials [17][18][19][20] were included in the review, all of which were included in the meta-analysis ( Figure 1). Four trials [17][18][19][20] were included in the review, all of which were included in the meta-analysis ( Figure 1).…”

“…26,27 Notably, this endpoint is more specific and less influenced by the nocebo effect than the occurrence of adverse events. 20 The selective enhancement of slow rather than fast inactivation of voltage-gated sodium channels operated by LCS might have also contributed, but no definitive conclusions could be drawn. The older age of the population enrolled in the trial and the higher rate of patients over 65 years might partially explain this finding.…”

Eslicarbazepine acetate as monotherapy in clinical practice: Outcomes from Euro-Esli

“…This may therefore reflect an improvement in overall tolerability as patients withdrew from AED polytherapy to monotherapy (since the majority of patients treated with ESL monotherapy at the last visit had previously received concomitant AED treatment[s] prior to withdrawing to ESL monotherapy). 2 Combining drugs that block voltage-dependent sodium channels is known to increase the likelihood of neurotoxic side effects (such as dizziness). These findings are consistent with those of a previous Euro-Esli subanalysis, which demonstrated that the incidence of AEs leading to discontinuation (as well as the overall incidence of AEs) was significantly lower in patients treated with less than two concomitant AEDs than in those treated with two or more concomitant AEDs.…”

“…2 These findings are supported by the results of two phase III withdrawal to monotherapy trials, 3,4 which resulted in approval for ESL in the monotherapy setting in the United States. 2 These findings are supported by the results of two phase III withdrawal to monotherapy trials, 3,4 which resulted in approval for ESL in the monotherapy setting in the United States.…”