Study of the Broad Clinical Benefit for Seroquel XR With Flexible Dose as an add-on Therapy in the Treatment of Acute Bipolar Mania Patients With Partial Response to Current Therapy

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the broad clinical benefit of dosing Seroquel XR with flexible in the treatment of acute bipolar mania patients with partial response to existing therapy. Clinical benefit will be assessed with the Clinical Global Impression-Clinical Benefit (CGI-CB) score, according to a classification based on the principles outlined in the CGI efficacy index. Improvement in clinical benefit will be defined as a decrease from baseline in CGI-CB.

Detailed Description
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A 4-week, Multi-Centre, Open-label, Non-comparative, Phase IV Study of the Broad Clinical Benefit for Seroquel XR (Quetiapine Fumarate Extended Release) With Flexible Dose as an add-on Therapy in the Treatment of Acute Bipolar Mania Patients With Partial Response to Current Therapy

Official Title
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A 4-week, Multi-Centre, Open-label, Non-comparative, Phase IV Study of the Broad Clinical Benefit for Seroquel XR (Quetiapine Fumarate Extended Release) With Flexible Dose as an add-on Therapy in the Treatment of Acute Bipolar Mania Patients With Partial Response to Current Therapy

Conditions
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Acute Bipolar Mania

Intervention / Treatment
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* Drug: Quetiapine fumarate (Seroquel XR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented clinical diagnosis meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria (1. Bipolar I Disorder, manic or mixed type with/without psychotic feature, 2. Diagnosis should be confirmed by the Mini Inte) Currently on Lithium/Valproate without antipsychotics more than 3 weeks consecutive treatment YMRS total score ≥16 at study entry Exclusion Criteria: Non-response to antipsychotic treatments for manic symptoms in previous episodes A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria (1. Unstable DM defined as enrolment glycosylated hemoglobin (HbA1c) >8.5%, 2. Admitted to hospital for treatment of DM or DM related illness in past 12 weeks, etc) An absolute neutrophil count (ANC) of 1.5 x 10^9 per liter

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine XR<br>Quetiapine fumarate (Seroquel XR) | Drug: Quetiapine fumarate (Seroquel XR)<br>* Extended Release(XR) 50 mg, 200 mg, 300 mg and/or 400 mg tablet, oral, once daily in the evening, from assignment to the end of the study.<br>* Other names: Seroquel XR tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Patients With Improvement From Baseline to Week 4 in Clinical Global Impression-Clinical Benefit Score (LOCF) | CGI-CB is used to evaluate the investigator's global weighted impression of efficacy and interference of adverse event from baseline to every visit. Improvement in clinical benefit is defined as a decrease from baseline in CGI-CB. Rank 1 denotes best possible benefit from new treatment and rank 10 indicates that there is no benefit from treatment. | Baseline, week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Change From Baseline to Week 4 in - YMRS (Young Mania Rating Scale) Total Score | The YMRS is an 11-item, multiple-choice diagnostic questionnaire which psychiatrists use to measure severity of manic episodes. There are 4 items graded on a 0 to 8 scale (irritability, speech, thought content, disruptive/aggressive behavior), and 7 items graded on 0 to 4 scale. These 4 items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. Typical YMRS baseline scores can vary a lot. They depend on patients' clinical features such as mania (YMRS = 12), depression (YMRS = 3), or euthymia (YMRS = 2. | Baseline, week 4 | 
| The CGI-I (Clinical Global Impression-Improvement of Illness) Change From Baseline to Week 4 | The Global Improvement scale (CGI-I) is scored to rate the patient's change from baseline CGI. A CGI-I score of 1 indicates that a patient is very much improved and a score of 7 indicates that a patient is very much worse. CGI-I scores greater than 4 indicate worsening, while scores less than 4 indicate improvement. At all following visits CGI-I will also be rated. The following calculations will be made: Proportion of patients with CGI Global Improvement rating ≤ 2 at Day 29 | Baseline, week 4 | 
| The Mean Change From Baseline to Week 4 in CGI-S (Clinical Global Impression-Severity of Illness) Score | The CGI-S is scored to rate patient's current clinical state. At enrolment patient's condition is rated using the CGI-S. At assignment CGI-S is again completed and a score of at least 4 (moderately ill). The score at assignment Day 1 will be regarded as the baseline value. At all following visits CGI-S will be rated. Each CGI item is scored on a scale from 1 to 7. A CGI-S score of 1 indicates that a patient is Normal, not at all ill and a score of 7 indicates that a patient is Among the most extremely ill patients. | Baseline, week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute bipolar mania, Seroquel XR, Quetiapine fumarate, Add-on therapy