An International, Multi-centre, Double-blind, Randomised, Parallel-group, Placebo-controlled, Phase III study of the Efficacy and Safety of Quetiapine Fumarate (Seroquel™, single oral 300 mg or 600 mg dose) and Lithium as Monotherapy in Adult Patients with Bipolar Depression for 8 weeks and Quetiapine in Continuation Treatment for 26 up to 52 weeks. - EMBOLDEN I

Conditions: Bipolar Depression

Registration Number: EUCTR2004-004681-33-DE

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 672

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).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 labo