Anti-epileptogenic Effects of Eslicarbazepine Acetate

NCT ID: NCT06597084

Last Updated: 2025-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 129 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-29
• Study Completion Date: 2023-09-11

Brief Summary

This study aims to assess if eslicarbazepine acetate (ESL) treatment (started within 96 hours after stroke occurrence and continued for 30 days) changes the incidence of unprovoked seizures (USs) within the first 6 months after randomisation as compared to placebo

Detailed Description

This is a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial in patients with acute intracerebral haemorrhage with a Cortical involvement, Age <65 years, Volume of intracerebral haemorrhage > 10 ml and Early seizure within 7 days after intracerebral haemorrhage (CAVE) score ≥ 3 or an acute ischaemic stroke with a SeLECT score ≥ 6.

At the first visit (screening/baseline, V1a), patients will undergo several examinations to check eligibility. The next visit (V1b) has to be performed within 96 hours after primary stroke occurrence. After eligibility has been confirmed, patients will be randomised (randomisation ratio 1:1) to treatment with ESL 800 mg (Group A) or placebo (Group B).

Patients will start treatment with the investigational medicinal product (IMP), i.e. ESL or placebo, within 96 hours after primary stroke occurrence at V1b. They will continue treatment until Day 30 after randomisation and then be tapered off. Thereafter, patients will be followed up until 18 months after randomisation. Patients can concomitantly receive antiepileptic therapies, except commercially available ESL or oxcarbazepine, until Day 30.

Concomitant antiepileptic therapies have to be discontinued and down-titration has to be started according to the respective Summary of Product Characteristics (SmPC). If the antiepileptic drugs (AEDs)/benzodiazepine are not already discontinued before, downtitration must be started on Day 31 at the latest.

If one or more AS(s) occur(s) within 7 days after primary stroke, this will not result in change of IMP dose. Patients having a first US will discontinue IMP treatment and will be treated at the discretion of the investigator until 18 months after randomisation, except with commercially available ESL.

Further visits will be performed 7 days (V2, on-site), 37 days (V3, on-site), 12 weeks (V4, telephone), 26 weeks (V5, on-site), 38 weeks (V6, telephone), 52 weeks (V7, on-site), 64 weeks (V8, telephone) and 78 weeks (End of Trial (EoT) visit, on-site) after V1b.

Conditions

Post Stroke Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group A

ESL 800 mg

Group Type: EXPERIMENTAL

ESL 800 mg

Intervention Type: DRUG

800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.

Group B

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.

Interventions

ESL 800 mg

800 mg ESL tablets for oral administration. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.

Intervention Type: DRUG

Placebo

Placebo tablets for oral administration, matching the test product. In case a patient is unable to swallow the whole tablet, the tablet can be crushed or divided into equal doses at the score line.

Intervention Type: DRUG

Other Intervention Names

Eslicarbazepine acetate, BIA 2-093

Eligibility Criteria

Inclusion Criteria

Patients must meet ALL of the following criteria:

1. Male or female patient aged 18 years or above;

2. Acute intracerebral haemorrhage with a CAVE score ≥ 3 or acute ischaemic stroke with a SeLECT score ≥ 6, in each case confirmed by magnetic resonance imaging (MRI)/computed tomography (CT).

3. Time of stroke occurrence is known and V1b is planned within 96 hours.

4. Brain scan analysis has reliably excluded structural brain lesions that can mimic stroke, e.g. cerebral tumour or brain abscess, etc.

5. a. Patient is able to give informed consent and to write and has signed written informed consent OR b. Patient is able to give informed consent, but unable to write and has provided verbal witnessed consent OR c. Patient is unable to give informed consent, but likely to regain this ability until V2, and the informed consent is deferred OR d. Patient is unable to give informed consent, but likely to regain this ability until V2, and patient's legal representative (according to the respective national/local requirements) has provided written informed consent.

6. Female patients without childbearing potential (2 years postmenopausal, bilateral oophorectomy or tubal ligation, or complete hysterectomy) are eligible. Female patients with childbearing potential must not be pregnant as confirmed by a negative pregnancy test and sexually active females must use a medically acceptable effective nonhormonal method of contraception up to the end of the current menstrual cycle after stopping treatment. Acceptable methods for women are surgical intervention (e.g. bilateral tubal occlusion), intrauterine device, double-barrier methods, true sexual abstinence (i.e. when this is in line with the preferred and usual lifestyle of the patient) and vasectomised male partner, provided that he is the sole partner of that patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

8. a. Patient is able to give informed consent and to write and has signed a written informed consent OR b. Patient is able to give informed consent, but unable to write and has provided verbal witnessed consent.

4. Sinus venous thrombosis.

5. Spontaneous sub-arachnoid haemorrhage due to e.g. aneurysmatic or arteriovenous malformation.

6. History of USs prior to primary stroke.

7. Impaired pre-stroke level of function, i.e. modified Rankin Scale (mRS) score > 3 prior to first stroke occurrence.

8. History of AED use before primary stroke within the last 5 years as defined in the list of not allowed AEDs.

9. Use of ESL, unless provided as IMP of this trial, and oxcarbazepine.

10. Severe hepatic impairment.

11. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (measured at V1a).

12. Known or suspected acute or chronic alcoholism, delirium tremens, or toxic psychosis.

13. History of suicidal ideation or suicide attempt within the past 3 years.

14. Presence of any other significant or progressive/unstable medical condition that, in the opinion of the investigator, would compromise evaluation of the trial treatment or may jeopardise the patient's safety, compliance or adherence to protocol requirements, such as significant psychiatric, cardiovascular, respiratory, metabolic, endocrine, haematologic, infectious or neurological disease.

15. For women: Pregnancy or breast-feeding.

16. Previous enrolment in this trial or participation in any other investigational drug trial within the past 30 days (or 5 half-lives of IMP whichever is longer) prior to V1a.

17. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.

18. Employees of the investigator or trial centre, with direct involvement in the proposed trial or other studies under the direction of that investigator or trial centre, as well as family members of the employees or the investigator.

Exclusion Criteria

Patients are to be excluded from the trial for ANY ONE of the following reasons:

1. Contraindication to ESL, i.e. known hypersensitivity to ingredients of ESL formulation or other carboxamide derivatives (e.g., oxcarbazepine, carbamazepine), or second or third degree atrioventricular (AV) block not corrected with a permanent pacemaker.

2. Known Han Chinese or Thai ancestry.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bial - Portela C S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eugen Trinka, MD MSc FRCP

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinik für Neurologie

Matthias Koepp, MD PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

UCL Institute of Neurology

Locations

Klinikum am Wörthersee, Abteilung fur Neurologie

Klagenfurt, FeschnigstraBe 11, Austria

Medizinische Universität Innsbruck, Universitätsklinik für Neurologie

Innsbruck, Innrain 52, Austria

Kepler University Hospital, Med Campus III, Department of Neurology 2

Linz, Krankenhausstraße 9, Austria

Clinical Research Center Salzburg GmbH

Salzburg, Strubergasse 21, Austria

Kepler University Hospital GmbH, Neuromed Campus, Department of Neurology 1

Linz, Wagner-Jauregg-Weg 15, Austria

Hospices Civils de Lyon, Neurological Hospitals

Bron, Boulevard Pinel, 59, France

UKGM Universitatsklinikum Marburg, Klinik und Poliklinik fur Neurologie

Marburg, Baldingerstrabe, Germany

Neurologische Universitatsklinik

Tübingen, Hoppe-Seyler-Strabe 3, Germany

Universitatsklinikum Essen, Klinik fur Neurologie

Essen, Hufelandstr. 55, Germany

LMU Ludwig-Maximilians-Universitat, Munchen, Klinikum Grobhadern, Neurologische Klinik und Poliklinik, Experimentelle Neurologie

München, Marchioninistrabe 15, Germany

Uniklinik RWTH Aachen, Klinik für Neurologie

Aachen, Pauwelsstr. 30, Germany

Universitatsklinikum Erlangen, Neurologische Klinik

Erlangen, Schwabachanlage 6, Germany

Sheba Medical Center, Neurology Department, Stroke Unit

Ramat Gan, Emek Ha'ella 1, Israel

Tel Aviv Sourasky Medical Center, Neurology Division

Tel Aviv, Weizmann 6, Israel

Clinica Neurologica e di Neuroriabllltazione - Azienda / Ospedallero-Universitarla S. Maria della Miserrcordia

Udine, P. Le S. Maria Della Misericordia, 15, Italy

Azienda Sanitaria Universitaria Integrata di Trieste - Ospedale Cattinara - Clinica Neurologica

Trieste, Strada Di Fiume 447, Italy

Azienda Sanitaria dell'Alto Adige - Ospedale di Merano

Merano, Via Rossini 5, Italy

Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital Santa Maria - Serviço de Neurologia

Lisbon, Avenida Prof. Egas Moniz, Portugal

Hospital Universitario Fundación Jiménez Diaz

Madrid, Avda. de Los Reyes Catolicos, 2, Spain

Sahlgrenska universitetssjukhuset, Neurosjukvarden

Gothenburg, Bia Straket 7, Sweden

King's College Hospital

London, Denmark Hill, United Kingdom

Institute of Neurology

London, Queen Square, United Kingdom

Countries

Austria; France; Germany; Israel; Italy; Portugal; Spain; Sweden; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: 0229_SAP_final_1.0_20231122

View Document

Other Identifiers

2018-002747-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BIA-2093-213

Identifier Type: -

Identifier Source: org_study_id