The purpose of this study is to investigate the efficacy and safety of eslicarbazepine acetate (BIA 2-093) as monotherapy for patients with newly diagnosed partial-onset seizures.
Epilepsy affects more than 50 million adults and children worldwide. Prevalence estimates in the total population vary from 4 to 8 per 1000 subjects. Anti-epileptic drugs (AEDs) are the major intervention and approximately 60% of newly diagnosed patients are seizure free on a single AED, but about 40% are not satisfactorily controlled and 25% suffer from significant adverse events (AEs). This lack of seizure control and unsatisfactory tolerability means there is still a need for new, effective AEDs that can be used as monotherapy. Given the efficacy of ESL in controlling partial onset seizures, the good tolerability and the convenience of QD dosing instead of twice daily (BID) dosing, ESL could offer a beneficial alternative as a first-line therapy in patients newly diagnosed with epilepsy experiencing partial-onset seizures. This study aims to demonstrate the efficacy and safety of ESL as a monotherapy treatment for this patient population proving non-inferiority to a standard therapy, Carbamazepine controlled release (CBZ-CR).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
815
Week 1 and 2 either 400mg/day Eslicarbazepine acetate (ESL) or 200mg/day Carbamazepine controlled release(CBZ-CR); Week 3 onwards either 800mg/day Eslicarbazepine acetate or 400mg/day CBZ-CR; this dose then to be maintained unless a subject has a seizure. Subjects experiencing a seizure will have their assigned treatment dose increased to ESL 1200mg/day or CBZ 800mg/day. Should a subject have another seizure, their assigned treatment is to be increased to ESL 1600mg/day or CBZ 1200mg/day. Subjects who remain seizure free for 26 weeks at any dose in an Evaluation Period will continue to receive the allocated treatment under double-blind conditions.
BIAL - Portela & Cª, S.A.
S. Mamede Do Coronado, S. Mamede Do Coronado, Portugal
The primary efficacy variable will be the proportion of subjects in the PP set who are seizure free for the entire 26-week Evaluation Period at the last received dose level.
Time frame: 26 weeks
Proportion of subjects in the ITT set without a seizure during the 26-week Evaluation Period at the last evaluated dose.
Time frame: 26 weeks
Proportion of subjects without a seizure during the 26-week Evaluation Period at the last evaluated dose.
Time frame: 26 weeks
Proportion of seizure-free subjects during 1 year of treatment at the last evaluated dose, where the end of the 1-year period is defined as the same start date as for the 26-week evaluation +365 days.
Time frame: 52 weeks
Time to first seizure at the last evaluated dose set.
Time frame: up to 183 weeks
QOLIE-31 and Bond-Lader VAS
Changes in quality of life assessed using the QOLIE-31 (Overall score, subscores covering emotional well-being, social functioning, energy/fatigue, cognitive functioning, seizure worry, medication effects and assessment of overall health).
Time frame: 26 weeks; up to 183 weeks
Treatment retention time at the last evaluated dose
Treatment retention time at the last evaluated dose, where treatment retention time is defined as the time of the first occurrence of one of the following: * Withdrawal of IMP due to AEs. * Withdrawal of IMP due to lack of efficacy.
Time frame: 26 weeks
Time to treatment failure at the first evaluated dose
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Time to treatment failure at the first evaluated dose, where time to treatment failure is defined as the time of the first occurrence of 1 of the following: * Seizure * Withdrawal of IMP due to AEs. * Withdrawal of IMP due to lack of efficacy.
Time frame: 26 weeks
seizure freedom
Dose level at which subjects reached 26-week seizure freedom.
Time frame: 26 weeks
Adverse Event monitoring
Incidence of AEs, SAEs, withdrawals, out-of-range laboratory values, abnormal 12-lead ECG and physical examination findings.
Time frame: up to 183 weeks