Bipolar I Disorder, Schizophrenia
Conditions
Keywords
Schizophrenia, Bipolar I Disorder
Brief summary
The purpose of this study is to demonstrate the efficacy and safety of quetiapine fumarate (SEROQUEL) in the treatment of adolescent patients with schizophrenia and bipolar I disorder.
Interventions
DRUGquetiapine fumarate
Oral dosing, flexible dosing
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patient is able to provide written assent and the parents or legal guardian of the patient are/is able to provide written informed consent before beginning any study related procedures * Patient previously enrolled in either double-blind Study D1441C00149 or D1441C00112 * Patient has documented clinical diagnosis of schizophrenia or bipolar I disorder * Patient's parent or legal guardian will be able to accompany the patient to each scheduled study visit
Exclusion criteria
* Patients (female) must not be pregnant or lactating * Patients with a known intolerance or lack of response to previous treatment with quetiapine * Patients who have previously participated in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Categorical Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Score | 26 weeks of treatment | Number of patients for who the total score is estimated as worse. The Barnes Akathisia Rating Scale (BARS) global score is used to measure Akathisia (a type of movement disorders). BARS is the item 4 score from the BARS assessment. The scale is from a range 0-5 (normal to worse). Change from baseline in BARS global score increase means worse. Improved defined as those with a \<= -1 change in BARS global score. Worsened defined as those with a \>= 1 change in BARS global score. |
| Changes in Laboratory Test Results (Prolactin) | Duration of study participation | Clinical important shift to high prolactin from open-label (OL) baseline to week 26. High Prolactin is defined as value \>26 ug/L for female and value \>20 ug/L for male. |
| Categorical Change From OL Baseline to Week 26 in Simpson-Angus Scale (SAS)Total Score | OL baseline to week 26 | Number of patients for who the total score is estimated as worse. The Simpson Angus Scale (SAS)is used to assess Parkinsonian symptoms (a type of movement disorders). The score was calculated as the sum of the 10 individual item scores. Total Score ranges from 0-40 (normal to worse). Individual item scale range from 0 to 4 (normal to worse). Improved define as those with a \<= -1 change in SAS total score. Worsened defined as those with a \>=1 change in SAS total score. |
| Change From Baseline in Weight | 26 weeks of treatment | Number with 7% or more increase (without adjustment for normal growth) |
| Change From Baseline in Supine Pulse | OL baseline to week 26 | Change from OL baseline to week 26 in supine pulse (bpm) |
| Change From OL Baseline in Supine Systolic BP. | OL baseline to Week 26 | Changes from OL baseline to the final visits in Supine systolic BP (mmHg) |
| Change From OL Baseline in Supine Diastolic BP. | OL baseline to Week 26 | Changes from OL baseline to the final visits in Supine diastolic BP (mmHg) |
| Incidence and Nature of Adverse Events (AEs) | from open label to week 26+ 30 days | Number of participants that had AE which occurred from first dose date to last dose date + 30 days. |
| Number of Patients Withdrawn Due to AEs. | during 26 weeks of treatment | Number of subjects who withdrew from the study due to AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Children's Global Assessment Scale (CGAS) Score | OL Baseline to Week 26 | Children's Global Assessment Scale (CGAS) is used to rate the general functioning of children under the age of 18. It is the 100-point single-item score that was collected in the Clinical Report Form (CRF), scored from 0-100 (worse to normal). |
| Changes in Tanner Stage | Change from OL baseline to week 26 in the Tanner stage | Category shift in Tanner stage. Number of subjects who experienced the change is presented. Tanner stages (I-V) was used to characterize physical development in children, adolescents, and adults. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger. |
Countries
India, Malaysia, Philippines, Poland, Russia, Serbia, South Africa, Ukraine, United States
Participant flow
Recruitment details
Enrollment was contingent on completing one of 2 short term efficacy studies, recruitment period August 2004 through July 2007 at 59 international clinical research sites
Pre-assignment details
Required to have completed one feeder study, either bipolar mania study D1441C00149 or schizophrenia study D1441C00112 and be willing to participate in a 26 week open label study and be between the ages of 10 and 18 years at the time of consent for this study, initial titration to maintain blind in feeder study
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine Quetiapine 400mg/day to 800mg/day | 380 |
| Total | 380 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 40 |
| Overall Study | Lack of Efficacy | 7 |
| Overall Study | LEAVING TOWN FOR 6 WEEKS | 1 |
| Overall Study | Lost to Follow-up | 33 |
| Overall Study | MOVED OUT OF AREA | 3 |
| Overall Study | NECESSITY OF USING ANTI DEPRESSANT | 1 |
| Overall Study | PERIOD SHORTENED FROM 6 wks to 4 wks | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Study specific discontinuation | 13 |
| Overall Study | Withdrawal by Subject | 42 |
Baseline characteristics
| Characteristic | Quetiapine |
|---|---|
| Age, Customized 10 - 12 years | 87 Participants |
| Age, Customized 13 - 18 years | 293 Participants |
| Diagnosis Bipolar | 205 participant from feeder studies |
| Diagnosis Schizophrenia | 175 participant from feeder studies |
| Sex: Female, Male Female | 154 Participants |
| Sex: Female, Male Male | 226 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 340 / 380 |
| serious Total, serious adverse events | 46 / 380 |
Outcome results
Primary
Categorical Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Score
Number of patients for who the total score is estimated as worse. The Barnes Akathisia Rating Scale (BARS) global score is used to measure Akathisia (a type of movement disorders). BARS is the item 4 score from the BARS assessment. The scale is from a range 0-5 (normal to worse). Change from baseline in BARS global score increase means worse. Improved defined as those with a \<= -1 change in BARS global score. Worsened defined as those with a \>= 1 change in BARS global score.
Time frame: 26 weeks of treatment
Population: Number of patients with BARS score at OL baseline and week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine | Categorical Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Score | 11 Participants |
Primary
Categorical Change From OL Baseline to Week 26 in Simpson-Angus Scale (SAS)Total Score
Number of patients for who the total score is estimated as worse. The Simpson Angus Scale (SAS)is used to assess Parkinsonian symptoms (a type of movement disorders). The score was calculated as the sum of the 10 individual item scores. Total Score ranges from 0-40 (normal to worse). Individual item scale range from 0 to 4 (normal to worse). Improved define as those with a \<= -1 change in SAS total score. Worsened defined as those with a \>=1 change in SAS total score.
Time frame: OL baseline to week 26
Population: Number of patients with SAS score at OL baseline and week 26.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine | Categorical Change From OL Baseline to Week 26 in Simpson-Angus Scale (SAS)Total Score | 34 Participants |
Primary
Change From Baseline in Supine Pulse
Change from OL baseline to week 26 in supine pulse (bpm)
Time frame: OL baseline to week 26
Population: Number of participants with OL baseline and post treatment visits
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine | Change From Baseline in Supine Pulse | 0.8 bpm | Standard Deviation 14.75 |
Primary
Change From Baseline in Weight
Number with 7% or more increase (without adjustment for normal growth)
Time frame: 26 weeks of treatment
Population: Number of participants is based on patients with both baseline values and post-baseline values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine | Change From Baseline in Weight | 134 Participants |
Primary
Change From OL Baseline in Supine Diastolic BP.
Changes from OL baseline to the final visits in Supine diastolic BP (mmHg)
Time frame: OL baseline to Week 26
Population: Number of participants with OL baseline and post treatment visits
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine | Change From OL Baseline in Supine Diastolic BP. | 1.3 mmHg | Standard Deviation 9.22 |
Primary
Change From OL Baseline in Supine Systolic BP.
Changes from OL baseline to the final visits in Supine systolic BP (mmHg)
Time frame: OL baseline to Week 26
Population: Number of participants with OL baseline and post treatment visits
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine | Change From OL Baseline in Supine Systolic BP. | 1.7 mmHg | Standard Deviation 11.52 |
Primary
Changes in Laboratory Test Results (Prolactin)
Clinical important shift to high prolactin from open-label (OL) baseline to week 26. High Prolactin is defined as value \>26 ug/L for female and value \>20 ug/L for male.
Time frame: Duration of study participation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine | Changes in Laboratory Test Results (Prolactin) | 19 Participants |
Primary
Incidence and Nature of Adverse Events (AEs)
Number of participants that had AE which occurred from first dose date to last dose date + 30 days.
Time frame: from open label to week 26+ 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine | Incidence and Nature of Adverse Events (AEs) | 321 Participants |
Primary
Number of Patients Withdrawn Due to AEs.
Number of subjects who withdrew from the study due to AEs.
Time frame: during 26 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine | Number of Patients Withdrawn Due to AEs. | 37 Participants |
Secondary
Change From Baseline in Children's Global Assessment Scale (CGAS) Score
Children's Global Assessment Scale (CGAS) is used to rate the general functioning of children under the age of 18. It is the 100-point single-item score that was collected in the Clinical Report Form (CRF), scored from 0-100 (worse to normal).
Time frame: OL Baseline to Week 26
Population: Number of patients with CGAS score at OL baseline and week 26.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine | Change From Baseline in Children's Global Assessment Scale (CGAS) Score | 7 units on a scale | Standard Deviation 13.9 |
Secondary
Changes in Tanner Stage
Category shift in Tanner stage. Number of subjects who experienced the change is presented. Tanner stages (I-V) was used to characterize physical development in children, adolescents, and adults. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.
Time frame: Change from OL baseline to week 26 in the Tanner stage
Population: Number of patients with Tanner stagging data at OL baseline and week 26 (final visit)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine | Changes in Tanner Stage | 70 Participants |