E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute manic episodes associated with bipolar I disorder in a double-blind, randomised, dose-titration, placebo-controlled, multicentre clinical trial
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the dose-dependent efficacy of two dose titration regimens of Eslicarbazepine Acetate compared with placebo as therapy in patients with acute mania.
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of two dose titration regimens of Eslicarbazepine Acetate in comparison to placebo.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patient must be / have: 18 years or more; DSM-IV criteria for Bipolar I Disorder (i.e., 296.0, 296.4 or 296.6) and for current acute manic (including mixed) episode, YMRS total score ≥ 20; symptoms of current manic episode starting within 2 weeks prior to Randomisation (V2, Day 1); able to undergo a standard evaluation including clinical interview, ratings and laboratory studies; signed informed consent form (ICF); post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; in case of woman of childbearing potential, patient presents a serum pregnancy test consistent with a non-gravid state and will use double-barrier contraception until at least the post-study visit. Concomitant medication: Patients currently treated with bipolar disorder preventive medication (for carbamazepine or oxcarbazepine see exclusion criteria) or antidepressants must be washed-out for at least two days prior to Randomization (V2, Day 1). Patients can only get randomized with lithium plasma levels < 0.5 mmol/L or valproic acid plasma level < 50 mg/L. Benzodiazepines should be permitted on the following lorazepam (or equivalent) doses: Dose 8 mg/day in Week 1, Dose 4 mg/day in Week 2 and Dose 2 mg/day in Week 3, but not within 4 hours before YMRS assessment.
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E.4 | Principal exclusion criteria |
Patients must not be/have: History of schizophrenia or schizoaffective disorder; psychotic features, history of rapid cycling; currently treated with carbamazepine or oxcarbazepine; history of unresponsiveness, intolerance or hypersensitivity to related compounds (carbamazepine, oxcarbazepine or licarbazepine); use of depot-neuroleptics in the current manic episode; abuse of stimulating drugs or use of systemic sympathicomimetic drugs within the previous 2 weeks; electroconvulsive therapy (ECT) within the previous 3 months; history of dependence or chronic abuse from alcohol, drugs or medications within the last year; clinically judged to be at risk of harm to self or others; second or third-degree atrioventricular blockade not corrected with a pacemaker; relevant ECG or laboratory abnormalities; calculated creatinine clearance < 30 mL/min; pregnancy or nursing; participation in other drug clinical trial within the last 2 months before randomization visit; not ensured capability to perform the trial or to comply with the study protocol (e.g. mental retardation or severe inability to communicate); any other uncontrolled clinically relevant disorder; previous treatment with Eslicarbazepine Acetate (BIA 2-093). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the YMRS score at the end of the 3-week treatment period, in relation to the baseline. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The maximum individual treatment duration is 3 weeks. Additional tapering-off period of up to 6 days in duration and a four-week follow-up period is planned in those patients who will not participate in the recurrence prevention study. Following Randomization (V2, Day 1), patients will have assessments on Day 4, Day 7, Day 10, Day 14 and Day 21. Those who will not participate in the extension study will have further assessments on V8 and PSV.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 16 |