Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory partial Seizures in a Double-Blind, Randomised, Placebo-Controlled, Parallel-Group, Multicentre Clinical Trial
A Double-Blind placebo controlled study of Eslicarbazepine acetate in patients with refractory partial Epilepsy.
Part I for a duration of 12 weeks.
The study treatment arms are as follows:
- Group 1: Placebo plus the subject and amp;apos;s existing anti-epilepsy medications
- Group 2: Eslicarbazepine acetate 800 mg once-daily (2 weeks at 400mg/day then 12 weeks at 800mg/day) plus the subject and amp;apos;s existing anti-epilepsy medications
- Group 3: Eslicarbazepine acetate 1200 mg once-daily (2 weeks at 800mg/day then 12 weeks at 1200mg/day) plus the subject and amp;apos;s existing anti-epilepsy medications.
Part I of the study will be composed of an 8-week baseline period (Period A), a 2-week
titration period (Period B), and a 12-week maintenance period (Period C). The 8-week baseline period will allow the characterisation of the patient compliance profile and to account for the number of seizures. The double-blind periods (Period B and C) will provide data regarding Eslicarbazepine acetate efficacy and safety in comparison with placebo. The 2-week titration period will allow a 1-step increase of Eslicarbazepine acetate doses up to the predefined dose, decreasing the chance of occurrence of adverse effects.
Part II: A 12-week maintenance period is the minimum time to establish whether efficacy is not short
lasting and historically it has been considered ethically acceptable to expose patients with
refractory epilepsy to placebo up to 12 weeks.
One to 2 concomitant AEDs are allowed in this study, which should be kept stable during
the course of the study. If present, the device for vagus nerve stimulation (VNS) should be
implanted at least 6 months before screening, stimulation parameters need to be stable for
at least 1 month prior to screening (VNS will not be counted as concomitant AED). The
blood drug assays of eslicarbazepine and those concomitant AEDs will allow the study of
potential drug-drug interactions.
Part III: In order to allow for the assessment of the maintenance of safety and absence of tolerance
during the long-term, a 1-year open-label extension was defined and at the end of the
1-year open-label extension, further extensions will be defined based on safety and
efficacy data until the drug is made available on the market or until clinical development is
discontinued. At the end of the 2-year open-label extension, further extensions will be
planned as needed if the drug is not available on the market yet or decisions about
discontinuing clinical development have not been reached. The Sponsor is responsible for
making this decision and if applicable a protocol amendment will be performed to allow
for the continuation of treatment with Eslicarbazepine acetate after V16. Per Amendment 5, if indicated the study drug will be titrated down in 400 mg. decrements in order to avoid an abrupt stop in a potentially therapeutic dose.
Criteria for Inclusion: At visit 1 (screening), patient must be/have: written informed consent signed by patient; aged 16 years (18 years of age at this site) or more,(no upper age limit); a documented diagnosis of epilepsy for at least 12 months prior to screening; at least 4 partial-onset seizures (including subtypes of simple partial, complex partial and/or partial seizures evolving to secondarily generalised) on the 4-weeks prior to screening; currently treated with 1 or 2 AEDs (any except OXC), in a stable dose regimen during at least 1 month prior to screening (patients using vigabatrin should have been on this medication for at least 1 year with no deficit in visual field identified, and a confirmatory test should be available within 1 month before study entry; if present, the device for vagus nerve stimulation (VNS) should be implanted at least 6 months before screening, parameters need to be stable for at least 1 month prior to screening (VNS will not be counted as concomitant AED); excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination (PE), and clinical laboratory test results; post-menopausal women or female patients otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; in case of women of childbearing potential (WOCBP), patient must present a serum beta-human chorionic gonadotropin (-hCG) test consistent with a non-gravid state and agree to remain abstinent or use reliable contraception (hormonal contraception should be combined with a barrier method) beginning at screening and continuing or at least untl 30 days after the last dose of study drug (the post-study visit.)
At visit 2 (randomisation), patient must have: at least 8 partial-onset seizures during the baseline with at least 3 partial-onset seizures in each 4-week section of the 8-week baseline period (documented in a diary) and no seizure-free interval exceeding 28 consecutive days; in case of WOCBP, patient must present a urine -hCG test consistent with a non-gravid state; diaries satisfactorily completed by the patient or his/her caregiver; satisfactorily complied with the study requirements during the baseline period (including no changes in concomitant AED therapy should have occurred in the baseline period).