Evaluate the Efficacy and Safety of Quetiapine Fumarate (SEROQUEL) Extended Release as Monotherapy in the Treatment of Patients With Bipolar Depression

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the superior efficacy of quetiapine extended release(XR) mono-therapy, administered once daily compared to placebo, in the treatment of depressive symptoms in patients with Bipolar I and Bipolar II Disorder

Official Title
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A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Quetiapine Fumarate (SEROQUEL) Extended Release as Monotherapy in the Treatment of Patients With Bipolar Depression

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: Quetiapine Fumarate (SEROQUEL) Extended Release
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Male and female patients, aged 18 to 65 years, inclusive. Meets Diagnostic and Statistical Manual of Mental Disorders - 4th Edition (DSM-IV) criteria for bipolar disorder I or bipolar II, most recent episode depressed (296.5x and 296.89x). Hamilton Rating Scale for Depression (HAM-D) (17-item) total score of ≥ 20 and HAM-D item 1 (depressed mood) score ≥ 2 at enrolment and randomisation. Patients must be able to understand and comply with the requirements of the study,as judged by the Investigator Exclusion Criteria: Patients with a current Diagnostic and Statistical Manual of Mental Disorders - 4th Edition (DSM-IV) diagnosis other than bipolar disorder Patients whose Young Mania Rating Scale (YMRS) total score >12 at enrolment and randomisation. Patients with >8 mood episodes during the past 12 months at enrolment. Patients whose current episode of depression exceeds 12 months or is less than 4 weeks from enrolment. Patients with a history of non-response to an adequate treatment (6 weeks) with more than 2 classes of antidepressants during their current episode. Alcohol or other substance dependence or abuse as defined by Diagnostic and Statistical Manual of Mental Disorders - 4th Edition (DSM-IV) criteria at enrolment that is not in extended full or extended partial remission (12 months or longer), except caffeine and nicotine dependence. Patients who, in the Investigator's judgment, pose a current serious suicidal or homicidal risk, have a Hamilton Rating Scale for Depression (HAM-D) item 3 score ≥ 3, or have made a suicide attempt within the past 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Quetiapine Fumarate (SEROQUEL) Extended Release<br>* Quetiapine fumarate extended release(XR) will be administered orally, once daily in the evening. The initial dose will be 50 mg. This dose will be adjusted on Day 2 to 100 mg, on Day 3 to 200 mg, and on Day 4 to 300 mg and after.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo matching quetiapine extended release(XR) 50 mg, 200 mg, and 300 mg tablets will be orally administered once daily, in the evening. The initial dose will be 50 mg. This dose will be adjusted on Day 2 to 100 mg, on Day 3 to 200 mg, and on Day 4 to 300 mg and after.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Visit 2) to End of Study (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | MADRS total score range: 0 to 60, the higher the score, the more severe, Change : Total MADRS score at week 8 minus score at baseline | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Response (Subjects With ≥50% Reduction From Baseline to Week 8 in MADRS Total Score) | Montgomery-Asberg Depression Rating Scale (MADRS) total score range: 0 to 60, the higher the score, the more severe, Response was defined as ≥50% reduction in MADRS total score from baseline | 8 weeks from baseline | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Total Score Remission (the Proportion of Subjects With a MADRS Total Score ≤ 12 at Week 8 Assessment) | Montgomery-Asberg Depression Rating Scale (MADRS) total score range: 0 to 60, the higher the score, the more severe, Remission was defined as MADRS total score ≤12 | After 8 week of start of treatment | 
| Change From Baseline to Each Assessment in MADRS Total Score | MADRS total score range: 0 to 60, the higher the score, the more severe. | Baseline to Week 8 | 
| Change From Baseline to Week 8 in HAM-D Total Scores | HAM-D total score range: 0 to 53, the higher the score, the more severe. Change : Total HAM-D score at week 8 minus score at baseline | Baseline to Week 8 | 
| Change From Baseline to Week 8 Assessment in the Clinical Global Impression Bipolar - Severity (CGI-BP-S) | CGI-BP severity of illness-Overall bipolar range = 1-7, the higher is the total score,the more severe is the disease. CGI-BP severity of illness-Depression range: 1-7, the higher is the total score, the more severe is the disease | Baseline to Week 8 | 
| The Proportion of Patients at Week 8 With a Clinical Global Impression - Bipolar - Change (CGI-BP-C) of Much or Very Much Improved | Clinical Global Impression - Bipolar - Change (CGI-BP-C) of much or Very much improved is defined as a change in CGI-BP overall bipolar illness score ≤ 2 where 1 = very much improved, 2 = much improved. | After 8 weeks of start of treatment | 
| Change From Baseline to Week 8 in Item 10 of Montgomery-Asberg Depression Rating Scale (MADRS) for Suicidal Ideation | MADRS item 10 (suicidal ideation) score range: 0 to 6, the higher the score, the more severe, Change: MADRS item 10 score at week 8 minus score at baseline | Baseline to Week 8 | 
| Incidence of Treatment-emergent Mania (AE of Mania or Hypomania, Defined as Young Mania Rating Scale [YMRS] Score ≥16 on 2 Consecutive Assessments or Final Assessment) | The incidence of treatment-emergent mania is defined as ≥16 of YMRS total score on 2 consecutive assessments or at final assessment, YMRS total score range: 0-60, the higher is the total score the more severe is the disease. | After 8 weeks of start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar Depression, Mental disease,