Anti-epileptogenic Effects of Eslicarbazepine Acetate

BIAL

Status and phase: Completed; Phase 2

Conditions: Post Stroke Epilepsy

Treatments: Drug: Placebo; Drug: ESL 800 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT06597084

2018-002747-29 (EudraCT Number)

BIA-2093-213

Details and patient eligibility

About

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

Full 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.

Enrollment: 129 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

   Inclusion criteria at V1b

7. V1b is within 96 hours after stroke occurrence. Inclusion criteria at V2 (only applicable for patients who were unable to give informed consent at V1a.)

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.

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.
3. History of previous stroke (other than the one described in inclusion criteria no. 2 - 3).
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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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129 participants in 2 patient groups, including a placebo group

Group A

Experimental group

Description:

ESL 800 mg

Treatment:

Drug: ESL 800 mg

Group B

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo