EFFICACY AND SAFETY OF ESLICARBAZEPINE ACETATE AS MONOTHERAPY FOR PATIENTS WITH NEWLY DIAGNOSED PARTIAL-ONSET SEIZURES
- Conditions
- Adult patients with newly diagnosed partial-onset seizuresMedDRA version: 18.0Level: LLTClassification code 10065336Term: Partial epilepsySystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2009-011135-13-BE
- Lead Sponsor
- BIAL - Portela & Ca, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 900
Visit 1 (Days –1 to –7; Screening)
1. Have signed an informed consent before undergoing any study-related activities. Subjects of Asian ancestry (subjects with a direct ancestor of Asian origin, irrespective of the generational difference) are required to give written informed consent for genotyping.
2. Male or female =18 years of age.
3. Newly diagnosed epilepsy with at least 2 well documented, unprovoked, clinically evaluated and classified partial seizures (with or without secondary generalization) with clear focal origin, documented clinically OR by electroencephalogram (EEG) OR imaging studies, within 12 months of Visit 1. In this context, seizures that occur within a period of 48 hours are counted as 1 seizure.
4. At least 1 seizure during the previous 3 months.
5. Demonstrated cooperation and willingness to complete all aspects of the study.
6. Female subjects without childbearing potential (2 years postmenopausal, bilateral oophorectomy or tubal ligation, or complete hysterectomy) are eligible. Female subjects with childbearing potential must not be pregnant as confirmed by a negative serum beta-human chorionic gonadotropin (hCG) test and sexually active females must be using a medically acceptable effective non-hormonal method of contraception for the duration of the study and until the Post-study visit (PSV).
Visit A1 (Day 1; Randomization and start of double-blind treatment period)
7. Have satisfactorily completed the electronic subject diary (eDiary).
8. Female subjects with childbearing potential must not be pregnant as confirmed by a negative urine pregnancy test and sexually active females must be using a medically acceptable effective non-hormonal method of contraception for the duration of the study and until the PSV.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 750
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150
Visit 1 (Days –1 to –7; Screening)
1.History of pseudo-seizures.
2.Seizures occurring only in clusters.
3.History of absence, myoclonic, clonic, tonic, or atonic seizures.
4.Documented EEG within 12 months of Visit 1 suggestive of primarily generalized epilepsy.
5.History of status epilepticus within the 3 months prior to Visit 1.
6.Known progressive neurologic disorder (progressive brain disease, epilepsy secondary to progressive cerebral lesion) as assessed by magnetic resonance imaging or computer tomography.
7.Former or current use of any AED, except for the use of a single AED for a maximum duration of 2 weeks before Visit 1.
8.Previous regular use of ESL or CBZ (previous use as acute treatment for seizures in an emergency situation is not an exclusion criterion).
9.Using mono-amine oxidase inhibitors (MAOIs), tricyclic antidepressants, nefazodone, isoniazid, or protease inhibitors or any other anti-retroviral agents (e.g. efavirez) that may raise the levels of CBZ-CR.
10.Known hypersensitivity to carboxamide derivatives or tricyclic antidepressants.
11.History of uncontrolled psychiatric illness or mood disorder requiring electro-convulsive or drug therapy within the previous 6 months, a history of suicide attempt, schizophrenia, chronic treatment with benzodiazepines (except short-acting benzodiazepines) or barbiturates.
12.Judged clinically to have a suicidal risk in the opinion of the investigator based upon a clinical interview and the Columbia Suicide-Severity Rating Scale (C-SSRS).
13.History of alcohol, drug, or medication abuse within the last 2 years.
14.Uncontrolled cardiac (including atrioventricular block and other clinically significant electrocardiographic abnormalities), renal, hepatic, endocrine, gastrointestinal, metabolic, hematological, or oncology disorder.
15.History of bone marrow depression.
16.History of hepatic porphyrias (e.g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda).
17.Relevant clinical laboratory abnormalities (e.g. sodium <130 mmol/L, alanine or aspartate transaminases >2 x the upper limit of normal, white blood cell count <3000 cells/mm3) (measured at Visit 1).
18.Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (measured at Visit 1).
19.Subjects of Asian ancestry who test positive for the presence of the HLA-B*1502 allele.
20.Pregnancy or lactating.
21.Participation in other drug clinical trial within the last 2 months or having received an IMP within 5 half-lives of that IMP, whichever is longer.
22.Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject’s ability to comply with the study protocol.
Visit A1 (Day 1; Randomization and start of double-blind treatment period)
23.Former or current use of any AED *, except for the use of a single AED for a maximum duration of 2 weeks before Visit 1 and with a drug-free period of at least 5 days before Visit A1. Benzodiazepines are allowed for an epileptic indication and as rescue medication during the =5-day drug-free period.
24.Using prohibited medication.
25.Pregnancy.
26.Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject’s ability to comply with the study protocol.
*For clarification, an acute treatment for a seizure during the study (e.g. in the emergency room) is allowed and is not considered a deviation.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate that monotherapy with Eslicarbazepine Acetate (ESL; 800 to 1600 mg once daily) is not inferior to monotherapy with controlled-release carbamazepine (CBZ-CR; 200 to 600 mg twice daily) in adults (=18 years) with newly diagnosed epilepsy experiencing partial-onset seizures.;Secondary Objective: To further demonstrate the efficacy, safety, and pharmacokinetics of ESL in this patient population at the doses used.;Primary end point(s): Proportion of subjects in the per protocol set who are seizure free for the entire 26-week Evaluation Period at the last received dose level.;Timepoint(s) of evaluation of this end point: time-frame 26 weeks
- Secondary Outcome Measures
Name Time Method