Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial‐onset seizures: Results of a phase <scp>III</scp>, double‐blind, randomized, placebo‐controlled trial

Sperling, Michael R.; Abou‐Khalil, Bassel; Harvey, Jay; Rogin, Joanne; Biraben, Arnaud; Galimberti, Carlo; Kowacs, Pedro André; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares‐da‐Silva, Patrício

doi:10.1111/epi.12894

Cited by 101 publications

(181 citation statements)

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“…The efficacy and safety/tolerability of ESL as adjunctive therapy were previously established in several clinical trials 2, 6, 7, 8. This study was designed to evaluate the effectiveness of ESL in the real‐world setting, with a more heterogeneous population in terms of treatment experiences and comorbidities.…”

Section: Discussionmentioning

confidence: 99%

“…The efficacy and safety/tolerability of ESL as adjunctive AED have been established in several randomized controlled trials (RCTs) 2, 6, 7, 8. 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.…”

Section: Introductionmentioning

confidence: 99%

“…When compared to the phase III trials,2, 6, 7, 8 this study will potentially allow us to evaluate a less refractory population by focusing on patients exclusively treated with one baseline AED.…”

Section: Introductionmentioning

confidence: 99%

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Eslicarbazepine acetate as adjunctive therapy in clinical practice: ESLADOBA study

Chaves¹,

Breia

Pimentel

et al. 2017

Acta Neurol Scand

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ObjectiveTo assess seizure control and tolerability of eslicarbazepine acetate (ESL) as adjunctive therapy to one baseline antiepileptic drug (AED), in adults with partial‐onset seizures (POS) with or without secondary generalization.MethodsMulticenter, non‐interventional, prospective cohort study conducted between March 2012 and September 2014 at 12 neurology departments in Portugal. Adults with POS not controlled with one AED who had initiated ESL as adjunctive treatment were enrolled. Retention rate was defined at the final visit (Vfinal) 6‐9 months of follow‐up. Proportion of responders, seizure‐free, changes in seizure frequency were evaluated using patients' diaries. Clinical Global Impression of Change (CGI‐C) and Clinical Global Impression of Severity (CGI‐S) were assessed by the neurologist.ResultsFifty‐two patients (48.1% male) were included with mean age 41.5±13.3 years. Mean epilepsy duration was 18.5±14.8 years; mean seizure frequency in the four previous weeks to baseline was 7.5±12.7. At Vfinal, retention rate was 73.0%; responder rate and seizure‐free rates were 71.1% and 39.5%, respectively. The median relative reduction in seizure frequency between baseline and Vfinal was 82.2%. A reduction in epilepsy severity (CGI‐S) was observed in 42.1%. According to CGI‐C, 73.6% patients had their epilepsy “much improved” or “very much improved”. Twelve patients (23.1%) had at least one adverse event (AE), two (3.9%) had one serious AE, and five (9.6%) discontinued due to AE.ConclusionsEslicarbazepine acetate showed good retention rates, elicited a significant reduction in seizure frequency, and was well tolerated when used in the clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Eslicarbazepine acetate as adjunctive therapy in clinical practice: ESLADOBA study

Chaves¹,

Breia

Pimentel

et al. 2017

Acta Neurol Scand

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“…The three ESL Phase 3 studies (2093‐301 [NCT00957684], 2093‐302 [NCT00957047], and 2093‐304 [NCT00988429], hereafter defined as Studies 301, 302, and 304; registered at ClinicalTrials.gov) were randomized, double‐blind, placebo−controlled, multicenter studies assessing the efficacy and tolerability of oral QD adjunctive ESL 400 mg (Studies 301 and 302 only), 800 mg, and 1200 mg 14, 15, 16. One thousand four hundred and 47 adult patients with at least four FOS within the 4‐week period prior to screening despite treatment with 1‐3 concomitant AEDs were randomized to treatment.…”

Section: Methodsmentioning

confidence: 99%

Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate

et al. 2018

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ObjectivesEslicarbazepine acetate (ESL) is a once‐daily (QD) oral antiepileptic drug (AED) for focal‐onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL.MethodsEslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200 mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses.ResultsEslicarbazepine PK was described by a one‐compartment model with linear absorption and elimination. The probability of a treatment‐emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800 mg than with an initial dose of ESL 400 mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline.ConclusionsPharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision‐making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions.

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“…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). It was noted in one study that switching from OXC to ESL (dose ratio 1:1) was associated with better tolerability during ESL treatment (Villanueva et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

Transition from oxcarbazepine to eslicarbazepine acetate: A single center study

2017

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ObjectivesThere is limited clinical evidence for comparison between oxcarbazepine (OXC) and eslicarbazepine acetate (ESL) in terms of tolerability, or how to execute the change from OXC to ESL. We report the process of transitioning patients with focal epilepsy from previous OXC treatment to ESL due to tolerability problems. The rationale for change from OXC is reported, and the outcome with respective to this rationale is analyzed in terms of tolerability and efficacy.Materials and MethodsThe subjects were transitioned overnight from OXC to ESL in a hospital inpatient setting. An evaluation of the effects of the transition was made after 1 and 3 months. All adverse events (AEs) were recorded following the transition period. Subjects were classified by outcome in terms of AEs.ResultsTwenty‐three subjects were transitioned from OXC to ESL. Fifteen patients OXC‐related AEs reduced significantly after transition. Particularly, most of (93%) the AEs presented in the morning resolved after transition to ESL. No patient had an increase in seizure frequency following the transition. The incidence of ESL‐related AEs was 39% at 1 month and 13% at 3 month follow‐up; however, all patients continued ESL throughout the study period.ConclusionsThis study demonstrates that patients suffering from OXC‐related AEs improve in terms of tolerability after a switch to ESL with maintaining seizure control. This improvement is more pronounced if the OXC‐related AEs are most evident following morning dosing of OXC. Transition can be safely executed in an outpatient setting.

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Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial‐onset seizures: Results of a phase III, double‐blind, randomized, placebo‐controlled trial

Cited by 101 publications

References 20 publications

Eslicarbazepine acetate as adjunctive therapy in clinical practice: ESLADOBA study

Eslicarbazepine acetate as adjunctive therapy in clinical practice: ESLADOBA study

Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate

Transition from oxcarbazepine to eslicarbazepine acetate: A single center study

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