Lipid profile with eslicarbazepine acetate and carbamazepine monotherapy in adult patients with newly diagnosed focal seizures: analysis of a phase III trial and open-label extension study

Background: Antiseizure medications can have negative effects on plasma lipid levels. Objectives: To evaluate plasma lipid changes in patients with newly diagnosed focal epilepsy treated with eslicarbazepine acetate (ESL) or controlled-release carbamazepine (CBZ-CR) monotherapy during a phase III, randomized, double-blind (DB) trial and 2 years of ESL treatment in an open-label extension (OLE). Design: Post hoc analysis of a phase III trial and OLE study. Methods: Proportions of patients with elevated levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were assessed at DB baseline, OLE baseline (last visit of DB trial), and end of OLE. Results: A total of 184 patients received ESL monotherapy during the OLE: 96 received ESL monotherapy in the DB trial and 88 patients received CBZ-CR monotherapy. The proportions of patients with elevated total cholesterol and LDL cholesterol increased significantly during the DB trial in those treated with CBZ-CR monotherapy [total cholesterol, +14.9% ( p  < 0.001); LDL cholesterol, +11.5% ( p  = 0.012)] but decreased significantly after switching to ESL monotherapy in the OLE [total cholesterol, −15.3% ( p  = 0.008); LDL cholesterol, −11.1% ( p  = 0.021)]. No significant changes were observed in those treated with ESL monotherapy during the DB trial and OLE. At the end of the DB trial, between-group differences (ESL–CBZ-CR) in the proportions of patients with elevated total and LDL cholesterol were −13.6% ( p  = 0.037) and −12.3% ( p  = 0.061), respectively; at the end of the OLE, these between-group differences were −6.0% ( p  = 0.360) and −0.6% ( p  = 1.000), respectively. Conclusion: A lower proportion of patients with newly diagnosed focal epilepsy had increased levels of total and LDL cholesterol, compared to baseline, following monotherapy with ESL versus CBZ-CR; after switching from CBZ-CR to ESL, the proportions of patients with increased levels decreased significantly. Registration: ClinicalTrials.gov NCT01162460/NCT02484001; EudraCT 2009-011135-13/2015-001243-36

Long-term efficacy and safety of eslicarbazepine acetate monotherapy for adults with newly diagnosed focal epilepsy: An open-label extension study

Objective: To assess the efficacy, safety, and tolerability of eslicarbazepine acetate (ESL) monotherapy during long-term treatment. Methods: An open-label extension (OLE) study was conducted in adults completing a phase 3, randomized, double-blind, noninferiority trial, during which they had received monotherapy with either once-daily ESL or twice-daily controlled-release carbamazepine (CBZ-CR) for newly diagnosed focal epilepsy. In the OLE study, all patients received ESL (800-1600 mg/d) for 2 years. Primary efficacy outcome was retention time (from baseline of the OLE study). Secondary efficacy assessments included seizure freedom rate (no seizures during the OLE study) and responder rate (≥50% seizure frequency reduction from baseline of double-blind trial). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs). Results: Of 206 randomized patients, 96 who received ESL in the double-blind trial (ESL/ESL) and 88 who received CBZ-CR in the double-blind trial (CBZ-CR/ESL) were treated with ESL monotherapy (89.3% overall). Treatment retention time was similar between groups, with low probability of ESL withdrawal overall (80% in both groups throughout the study. Incidence of serious TEAEs was similar between groups (7.3% vs 5.7%; 0% vs 1.1% possibly related), as were the incidences of TEAEs considered at least possibly related to treatment (17.7% vs 18.2%) and TEAEs leading to discontinuation (3.1% vs 4.5%). The types of TEAEs were generally consistent with the known safety profile of ESL. Significance: ESL monotherapy was efficacious and generally well tolerated over the long term, including in patients who transitioned from CBZ-CR monotherapy. No new safety concerns emerged