E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bipolar I disorder, manic and mixed episodes |
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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 demonstrate the efficacy of licarbazepine 750-2500 mg/d combined with risperidone in the treatment of manic episodes of bipolar I disorder by testing the following hypothesis: Licarbazepine combined with risperidone is superior to placebo combined with risperidone in the reduction of the mean total score of the Young Mania Rating Scale (Y-MRS) from baseline to endpoint (Week 6).
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E.2.2 | Secondary objectives of the trial |
To study the safety and tolerability of licarbazepine 750-2500 mg/d combined with risperidone in patients with manic episodes of bipolar I disorder by comparing licarbazepine combined with risperidone to placebo combined with risperidone with respect to the rates of adverse events and serious adverse events, as well as changes in laboratory values, ECGs and vital signs during the 6-week treatment. To determine the efficacy of licarbazepine 750-2500 mg/d combined with risperidone in the treatment of manic episodes of bipolar I disorder by testing the following hypothesis: Licarbazepine combined with risperidone is superior to placebo combined with risperidone in the proportion of patients with a 50% reduction of the baseline Y-MRS at endpoint.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• males and females 18 through 70 years of age; • diagnosis of bipolar disorder type I, manic or mixed episode according to DSM-IV criteria (i.e., 296.0, 296.4 or 296.6), including patients with/without psychotic features or with/without a history of rapid cycling; • total score of at least 20 on the Young Mania Rating Scale (Y-MRS); • need of psychiatric treatment; |
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E.4 | Principal exclusion criteria |
• current DSM-IV Axis-I diagnosis other than bipolar I disorder; • history of schizophrenia or schizoaffective disorder; • concomitant use of psychoactive medication other than risperidone and lorazepam, whereby the time between the last dose of prior medication and the baseline visit is dependent on the medication; • drug dependence during the one month prior to screening. Drug dependence is defined by DSM-IV criteria; • positive urine drug screen at screening visit for amphetamines, cocaine, hallucinogens or opiates; • history of suicide attempt within the month prior to the screening visit or immediate risk of harm to self or others at the time of screening, as judged by the Investigator; • mental retardation (according to DSM-IV criteria); • female patients of childbearing potential who are not using effective contraception during the study, are breast feeding, or have a positive pregnancy test ( hCG) at screening or baseline; • any non-psychiatric coexistent illness (e.g., diabetes mellitus, hypothyroidism) that has not been maintained in a stable condition for at least 3 months prior to baseline; • clinically significant abnormal conditions of the gastrointestinal system, liver, or kidneys, which could result in the possibility of altered absorption, excess accumulation, or impairment of metabolism or excretion of the study drug; • twice the upper normal limit at screening and upon repeated measurement for any one of the following laboratory parameters: SGOT, SGPT, LDH, alkaline phosphatase, or bilirubin BUN values 30 mg/dL or creatinine clearance < 30 ml/min; • any other clinically significant abnormal laboratory findings at screening which remain abnormal upon repeated measurement; • any of the following serological findings: - a positive hepatitis A antibody (IgM); - a positive hepatitis B surface antigen (HBsAg); - a positive hepatitis B core antibody (Anti-HBcAb), along with a negative hepatitis B surface antibody (Anti-HBsAb), in the setting of abnormal liver enzymes or recent clinical symptoms of hepatitis (within the last 2 months); • current diagnosis or recent past history of epilepsy, major head trauma, or progressive neurological disease (e.g., Parkinson’s disease, ALS); • electroconvulsive therapy (ECT) within the one months preceding baseline; • any form of psychotherapy within the one month preceding baseline; |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: The primary efficacy variable is the change from baseline to endpoint (Week 6) in the total score of the Y-MRS.
Safety: The assessment of safety will be based mainly on the frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g. electrocardiogram, vital signs, and special tests) will be analyzed when appropriate.
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
active comparator as add-on |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |