Acute Bipolar Mania
Conditions
Keywords
Acute bipolar mania, Seroquel XR, Quetiapine fumarate, Add-on therapy
Brief summary
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
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
Interventions
DRUGQuetiapine fumarate (Seroquel XR)
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.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Patients With Improvement From Baseline to Week 4 in Clinical Global Impression-Clinical Benefit Score (LOCF) | Baseline, week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Change From Baseline to Week 4 in - YMRS (Young Mania Rating Scale) Total Score | Baseline, week 4 | 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. |
| The CGI-I (Clinical Global Impression-Improvement of Illness) Change From Baseline to Week 4 | Baseline, 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 |
| The Mean Change From Baseline to Week 4 in CGI-S (Clinical Global Impression-Severity of Illness) Score | Baseline, week 4 | 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. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine XR Extended Release (XR) 50mg, 200mg 300mg and/or 400mg tablet, oral once daily in the evening, from assignment to the end of the study | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screening Failed | 2 |
| Overall Study | Treatment Withdrawn | 6 |
Baseline characteristics
| Characteristic | Quetiapine XR |
|---|---|
| Age, Customized <=18 years | 0 participants |
| Age, Customized >=65 years | 0 participants |
| Age, Customized Between 18 and 65 years | 27 participants |
| Age, Customized Unknown | 5 participants |
| Region of Enrollment Korea, Republic of | 32 participants |
| Sex/Gender, Customized Female | 18 participants |
| Sex/Gender, Customized Male | 10 participants |
| Sex/Gender, Customized Unknown | 4 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
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.
Time frame: Baseline, week 4
Population: As the study was terminated prematurely none of the randomized patients have been analysed.
Secondary
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
Time frame: Baseline, week 4
Secondary
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.
Time frame: Baseline, week 4
Secondary
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.
Time frame: Baseline, week 4