Efficacy and safety of eslicarbazepine acetate as add‐on treatment in patients with focal‐onset seizures: Integrated analysis of pooled data from double‐blind phase III clinical studies

Abstract

SUMMARYPurpose: To evaluate the efficacy and safety profile of eslicarbazepine acetate (ESL) added to stable antiepileptic therapy in adults with partial-onset seizures. Methods: Data from 1,049 patients enrolled from 125 centers, in 23 countries, in three phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2-week titration period, ESL was administered at 400 mg, 800 mg, and 1,200 mg once-daily doses for 12 weeks. Key Findings: Seizure frequency was significantly reduced with ESL 800 mg (p < 0.0001) and 1,200 mg (p < 0.0001) compared to placebo. Median relative reduction in seizure frequency was, respectively, 35% and 39% (placebo 15%) and responder rate was 36% and 44% (placebo 22%). ESL was more efficacious than placebo regardless of gender, geographic region, epilepsy duration, age at time of diagnosis, seizure type, and number and type of concomitant antiepileptic drugs (AEDs). Incidence of adverse events (AEs) and AEs leading to discontinuation were dose dependent. AEs occurred mainly during the first weeks of treatment, with no difference between groups after 6 weeks. Most common AEs (>10% patients) were dizziness, somnolence, and headache. The incidence of AEs in ESL groups compared to placebo was generally consistent among different subpopulations. Significance: Once-daily ESL 800 mg and 1,200 mg showed consistent results across all efficacy and safety end points. Results were independent of study population characteristics and type and number of concomitant AEDs.

Eslicarbazepine acetate as adjunctive therapy in clinical practice: ESLADOBA study

“…Compared to other studies that use ESL as adjunctive therapy, this rate is lower than the ones reported in EPOS study (26.0%),17 Correia et al. (42.1%),16 and that obtained in a pooled analysis of three phase III trials (62.7% and 67.5% in the ESL 800 mg and 1.200 mg groups, respectively) 9. Most of the frequent AEs reported in our study (Table 2) were also different from the ones published on phase III clinical trials 20…”

“…(13.4%),18 and in Correia et al. (21.1%) studies,16 and in the integrated analysis of pooled data from the phase III clinical trials (approximately 14.0%) 9. Compared to our study, there were differences in the follow up period, patients' characteristics and sample size, which might explain the different results.…”

“…In general, the patients enrolled in these studies had long‐standing epilepsy (mean duration in three phase III trials was equal to or over 22 years in all treatment groups,9 a high seizure frequency in the four prior weeks to screening,8, 9 and the majority was treated with two concomitant AEDs8, 9), indicating that the populations included severe refractory patients.…”

Assessing long-term effects of eslicarbazepine acetate on lipid metabolism profile, sodium values and liver function tests

“…Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) indicated for the treatment of focal onset seizures with or without tonic-clonic bilateral evolution (Gil-Nagel et al, 2013). After intake, ESL is extensively (<95%) hydrolyzed to eslicarbazepine .…”

Transition from oxcarbazepine to eslicarbazepine acetate: A single center study

“…Eslicarbazepine acetate is efficacious and well tolerated as adjunctive therapy in drug‐resistant focal epilepsies at doses of 800 and 1,200 mg once‐daily (Ben‐Menachem et al., 2010; Elger et al., 2009; Gil‐Nagel, Lopes‐Lima, Almeida, Maia, & Soares‐Da‐silva, 2009; Gil‐Nagel et al., 2013; Sperling et al., 2015). Dizziness, vertigo, abnormal coordination, ataxia, diplopia, fatigue, somnolence, and headache are most often reported and frequent AEs in controlled clinical trials (Sperling et al., 2015) and to a lesser degree when used as the only adjunctive AED (Holtkamp, McMurray, Bagul, Sousa, & Kockelmann, 2016).…”