Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Epilepsy
23 juin 2014 mis à jour par: Bial - Portela C S.A.
Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Clinical Trial
The primary objective was to evaluate the efficacy of eslicarbazepine acetate (ESL) administered once daily at 1200 mg or 800 mg, compared with placebo as adjunctive therapy in patients with refractory partial epilepsy over a 12-week maintenance period.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This was a phase III, 2-part multicenter study. Part I was an 26-week parallel-group, randomized, placebo-controlled design consisting of an 8 week baseline period, a 2 week double-blinded titration period, 12 week maintenance period, and a 4 week tapering-off period. After completing the baseline period, patients were randomized in a 1:1:1 ratio to 1 of the 2 ESL daily dose levels (1200 or 800 mg) or placebo.
Part II was a 1-year open-label extension for patients who had completed Part I. Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day. Patients who completed Part II could participate in a study extension and continue treatment with ESL until marketing authorization is obtained or clinical development is discontinued, with visits scheduled at the discretion of the investigator but at least every 6 months.
Results from Part I & II were presented in two separate reports.
Type d'étude
Interventionnel
Inscription (Réel)
253
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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S. Mamede do Coronado, Le Portugal, 4745-457
- Bial - Portela & Cª, S.A.
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- written informed consent signed by patient
- aged 18 years or more
- documented diagnosis of simple or complex partial seizures with or without secondary generalisation since at least 12 months prior to screening
- at least 4 partial seizures in each 4 week period during the last 8 weeks prior to screening, currently treated with 1 or 2 AEDs (any except oxcarbazepine and felbamate), in a stable dose regimen during at least 2 months prior to screening (patients using vigabatrin should have been on this medication for at least 1 year with no deficit in visual field identified)
- excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination and laboratory tests
- post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; in case of woman of childbearing potential, patient must present a serum beta-hCG test consistent with a non-gravid state and agree to remain abstinent or use reliable contraception (oral contraception should be combined with a barrier method)
Exclusion Criteria:
- only simple partial seizures with no motor symptomatology (classified as A2-4 according to the International Classification of Epileptic Seizures) that are not video-EEG documented
- primarily generalised epilepsy
- known rapid progressive neurological disorder; history of status epilepticus or cluster seizures (i.e., 3 or more seizures within 30 minutes) within the 3 months prior to screening
- seizures of psychogenic origin within the last 2 years
- history of schizophrenia or suicide attempt
- currently on or with exposure to felbamate or oxcarbazepine more within one month of screening
- using benzodiazepines on more than on an occasional basis (except when used chronically as AED)
- previous use of ESL or participation in a clinical study with ESL
- known hypersensitivity to carbamazepine, oxcarbazepine or chemically related substances
- history of abuse of alcohol, drugs or medications within the last 2 years
- uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder
- second or third-degree atrioventricular blockade not corrected with a pacemaker
- relevant clinical laboratory abnormalities
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: ESL 800 mg daily (Part I)
ESL 800mg daily
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oral tablet, 800 mg or 1200 mg once daily
Autres noms:
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Expérimental: ESL 1200 mg daily (Part I)
ESL 1200mg daily
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oral tablet, 800 mg or 1200 mg once daily
Autres noms:
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Comparateur placebo: placebo (Part I)
placebo
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once daily placebo comparator
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Expérimental: ESL - Open-label Extension (Part II)
All patients were treated with only ESL during Part II.
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Part II was a 1-year open-label extension for patients who had completed Part I. Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Seizure Frequency
Délai: 12 weeks
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The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks.
The primary efficacy analysis was based on results for the ITT population during the 12-week maintenance period.
Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA model with treatment as a factor and seizure frequency as a covariate
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12 weeks
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PART II: Nº of Treatment-Emergent Adverse Events (TEAE)
Délai: 1-year
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The primary objective for Part II of the study was to evaluate the safety and tolerability of eslicarbazepine acetate (ESL, BIA 2-093) at doses titrated to an efficacy or safety endpoint over a 1-year open-label period.
Safety assessments were based primarily on AEs (Number of participants with at least one treatment-emergent adverse events are reported); assessment of AEs was based on treatment relatedness, action taken on study drug, outcome, and causality.
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1-year
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Antonio Gil-Nagel, MD, Hospital Ruber Internacional La Masó 38, Mirasierra 28034 Madrid, Spain
- Chercheur principal: Jose Lopes-Lima, MD, Hospital Santo António Largo Prof. Abel Salazar, 4099-001 Porto, Portugal
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 décembre 2004
Achèvement primaire (Réel)
1 juin 2008
Achèvement de l'étude (Réel)
1 juin 2008
Dates d'inscription aux études
Première soumission
10 août 2009
Première soumission répondant aux critères de contrôle qualité
11 août 2009
Première publication (Estimation)
12 août 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
2 juillet 2014
Dernière mise à jour soumise répondant aux critères de contrôle qualité
23 juin 2014
Dernière vérification
1 juin 2014
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies du cerveau
- Maladies du système nerveux central
- Maladies du système nerveux
- Épilepsie
- Epilepsies partielles
- Mécanismes moléculaires de l'action pharmacologique
- Modulateurs de transport membranaire
- Anticonvulsivants
- Bloqueurs de canaux sodiques voltage-dépendants
- Bloqueurs des canaux sodiques
- Acétate d'eslicarbazépine
Autres numéros d'identification d'étude
- BIA-2093-303
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