| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| 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 superior efficacy of quetiapine compared with placebo in the acute treatment of patients with bipolar depression. | |
| E.2.2 | Secondary objectives of the trial | The secondary objectives relating to the acute treatment of patients with bipolar depression are:
1.to demonstrate the efficacy of quetiapine in reducing suicidal ideation in acute treatment of patients with bipolar depression.
2.to demonstrate the efficacy of quetiapine in reducing anxiety symptoms in acute treatment of patients with bipolar depression.
The secondary objectives relating to the continuation treatment of patients with bipolar depression are:
1.to demonstrate the efficacy of quetiapine versus placebo in increasing time to recurrence of a mood event during continuation treatment of patients with bipolar depression. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | 1.Provision of written informed consent before initiation of any study related procedures.
2.Male and female patients aged 18 to 65 years, inclusive.
3.Documented clinical diagnosis meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV, American Psychiatric Association, 1994) criteria for bipolar I disorder or bipolar II disorder, most recent episode depressed (296.50-296.54 and 296.89 respectively) confirmed by the amended version of the Structured Clinical Interview for DSM-IV (SCID).
4.HAM-D (17-item) total score of ≥20 and HAM-D item 1 (depressed mood) score ≥2 at Visit 1 (Enrolment) and 2 (Randomisation).
5.Be able to understand and comply with the requirements of the study, as judged by the investigator.
6.Outpatient status at Visit 1 (Enrolment) and at Visit 2 (Randomisation).
| |
| E.4 | Principal exclusion criteria | 1.Patients with a current DSM-IV Axis I disorder other than bipolar disorder that is symptomatic or requiring treatment within 6 months of enrolment.
2.YMRS total >12 at enrolment or randomisation.
3.Patients with more than 8 mood episodes during the past 12 months.
4.Patients whose current episode of depression exceeds 12 months or is less than 4 weeks from enrolment.
5.History of non-response to an adequate treatment (6 weeks) with more than 2 classes of antidepressants during their current episode.
6.Substance/alcohol dependence or abuse at enrolment (except dependence in full remission (>12 months) and except caffeine and nicotine dependence) as defined by DSM-IV criteria. Patients with a positive urine toxicology screen will be excluded only if they satisfy the DSM-IV criteria for abuse or dependence. However, a single urine toxicology screen for cocaine, heroin or PCP will lead to exclusion.
7.Use of drugs that induce or inhibit the hepatic metabolising cytochrome P450 3A4 enzymes within 2 weeks prior to randomisation or during the randomisation period (see Section 3.7.3, Table 7)
8. Use of the following medication:
-antipsychotic, mood stabilizer, antidepressant, anxiolytic, hypnotic or other psychoactive drugs (except hypnotics as described in Table 5, section 3.7.3) within 5 days before randomisation
-fluoxetine within 28 days before randomisation
-extended release risperidone within 14 days before randomisation
-a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
-lithium within 7 days before randomisation and/or tapering off started less than 14 days before randomisation
9.Patients who in the investigators opinion will require formalised psychotherapy during the study period, unless psychotherapy has been ongoing for a minimum of 3 months prior to randomisation.
10.Patients who, in the investigator’s judgment pose a current serious suicidal or homicidal risk, have a HAM-D item 3 score of 3 or greater, or have made a suicide attempt within the past 6 months.
11.Pregnancy or lactation. Female patients of childbearing potential must have a negative serum pregnancy test at enrolment and be willing to use a reliable method of birth control, ie, double-barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal ligation, during the study.
12.A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
-Unstable DM defined as enrolment HbA1c >8.5%.
-Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
-Not under care of physician responsible for patient’s DM care.
-Physician responsible for patient’s DM care has not indicated that patient’s DM is controlled.
-Physician responsible for patient’s DM care has not approved patient’s participation in the study.
-Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the four (4) weeks prior to randomisation. For thiazolidinediones (glitazones) this period should not be less than 8 weeks.
-Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks.
Note: If a diabetic patient meets one of these criteria the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
13.Clinically significant deviation from the reference range in clinical laboratory test results at enrolment as judged by the investigator.
14.Evidence of clinically relevant disease or a clinical finding that is unstable or that, in the opinion of the investigator, would be negatively affected by study medication or that would affect study medication.
15.Patients with renal impairment (serum creatinine ≥1.5 mg/dL) or hepatic impairment (ALT or AST 3 times the upper limit of normal).
16.A thyroid-stimulating hormone (TSH) concentration more than 10% above the upper limit of the normal range of the laboratory used for sample analysis whether or not the patient is being treated for hypothyroidism.
17.ECG result considered to be clinically significant as determined by the investigator based on assessment by a centrally located experienced cardiologist interpreting the ECG obtained using centralised trans-telephonic ECG methods.
In addition, the following is regarded as a criterion for exclusion from the continuation phase of the study.
26.A score of >12 on the MADRS or >12 on the YMRS at Week 8. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The change from randomisation to Week 8 assessment in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. | |
| 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 | No |
| 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) | Yes |
| 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 | |
| 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
