Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy

Ben‐Menachem, Elinor; Gabbai, Alberto Alain; Hufnagel, A.; Maia, Joana; Almeida, Luís; Soares-da-Silva, Patrı́cio

doi:10.1016/j.eplepsyres.2010.01.014

Cited by 172 publications

(215 citation statements)

References 15 publications

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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%

“…A population PK model for eslicarbazepine was previously developed13 using data from Phase 3 Studies 301, 302, and 30314, 15, 17 and was later refined using data from 11 Phase 1 studies and three Phase 3 studies (Studies 301, 302, and 304). Data from 500/1039 of the subjects included in the current model were also included in the previously developed model.…”

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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Suicidality Risk of Newer Antiseizure Medications

et al. 2021

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IMPORTANCE Most antiseizure medications (ASMs) carry a US Food and Drug Administration-mandated class label warning of increased suicidality risk, based on a meta-analysis comparing suicidality between individuals treated with medications vs placebo in randomized clinical trials done before 2008. ASMs approved since then carry this warning although they were not similarly studied.OBJECTIVE To review all placebo-controlled phase 2 and 3 studies of 10 ASMs approved since 2008 to evaluate the risk of suicidality of these drugs compared with placebo.DATA SOURCES Primary publications and secondary safety analyses in PubMed of all phase 2 and 3 randomized placebo-controlled epilepsy trials of ASMs approved since 2008, using keywords epilepsy, antiepileptic drugs, seizures, suicidality, suicidal ideation, and the names of individual drugs.STUDY SELECTION All phase 2 and 3 randomized clinical trials of adjunctive treatment of drug-resistant epilepsy and their secondary safety analyses.DATA EXTRACTION AND SYNTHESIS Articles were reviewed for frequency of suicidality (ideation, attempts, and completed suicides). Mode of suicidality ascertainment included treatment-emergent adverse event reports, Standardized Medical Dictionary for Regulatory Activities queries for events in prespecified categories including suicidal ideation and behavior, prospective collection of suicidality data as a prespecified safety outcome using the Columbia-Suicide Severity Rating Scale, and retrospective evaluation by blinded review using the Columbia-Classification Algorithm of Suicide Assessment. A meta-analysis compared risk for drugs vs placebo of each outcome for all drugs overall and by individual drugs and trials.MAIN OUTCOMES AND MEASURES Suicidality (total and by ideation), attempts, and completed suicides.RESULTS Excluding studies that did not evaluate suicidality (everolimus and fenfluramine) or did not evaluate it prospectively (lacosamide, ezogabine, and clobazam), 5 drugs were analyzed: eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. Suicidality was evaluated in 17 randomized clinical trials of these drugs, involving 5996 patients, of whom 4000 patients were treated with ASMs and 1996 with placebo. There was no evidence of increased risk of suicidal ideation (drugs vs placebo overall risk ratio, 0.75; 95% CI, 0.35-1.60) or attempt (risk ratio, 0.75; 95% CI, 0.30-1.87) overall or for any individual drug. Suicidal ideation occurred in 12 of 4000 patients treated with ASMs (0.30%) vs 7 of 1996 patients treated with placebo (0.35%) (P = .74). Three patients treated with ASMs and no patients treated with placebo attempted suicide (P = .22). There were no completed suicides.CONCLUSIONS AND RELEVANCE There is no current evidence that the 5 ASMs evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning.

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Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy

Cited by 172 publications

References 15 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

Suicidality Risk of Newer Antiseizure Medications

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