Bipolar Disorder
Conditions
Keywords
Aripiprazole, Bipolar I Disorder, Manic or Mixed Episode with or without Psychotic Features
Brief summary
The purpose of this trial is to test the safety and efficacy of two doses of aripiprazole in child and adolescent patients with bipolar I disorder, manic or mixed episode with or without psychotic features.
Interventions
DRUGAripiprazole
Treatment Arm 1 (10 mg treatment arm): Aripiprazole 2 mg QD for 2 days, aripiprazole 5 mg QD for 2 days, and aripiprazole 10 mg QD as the target dose starting on Day 5. Subjects remained on the 10 mg dose for the remainder of the treatment period Subjects reached their target dose through a forced titration schedule and proceeded with treatment at their target dose until Week 4. If the subject reached Week 4, he or she continued into the Extension Phase, a 6-month double-blind treatment period, beginning at the same dose taken at the end of the Acute Phase.
DRUGplacebo
Placebo tablet
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Child and adolescent patients with bipolar I disorder, manic or mixed episode with or without psychotic features
Exclusion criteria
* Patients with certain other psychological disorders * Patients with a co-morbid serious, uncontrolled systemic illness * Patients with significant risk of committing suicide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 4 | Baseline and Week 4 | Change from Baseline to Week 4 in Y-MRS total score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through the continuation phase.) The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 grades of severity. Minimum score on the scale is 0 (absent or normal). Maximum score on the scale is 60 (worse outcome or more severe symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Children's Global Assessment Scale (CGAS) Total Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in CGAS total score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGAS is a 100-point scale measuring psychological, social, and school functioning for children aged 6 to 17 years. Minimum scores ranged from 1-10, representing the need for constant supervision (worse outcome) to maximum scores of 91-100, representing superior functioning (better outcome). |
| Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in CGI-BP mania score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe). |
| Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in CDRS-R score, using last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CDRS-R is used to diagnose depression and monitor treatment response. The interviewer rates 17 symptom areas (including those that sever as DSM-IV criteria for diagnosis of depression), among them suicidal ideation. Minimum score on the scale is 17 (better outcome). Maximum score on the scale is 113 (worse outcome or more severe symptoms). |
| Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in GBI Total Parent/Guardian Version Mania score, using LOCF. Assessments performed baseline and weekly through acute phase (Week 4). (Also at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) GBI is self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale was completed by parent/guardian. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome. |
| Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in ADHD-RS-IV Total score, using last observation carried forward. Assessments performed at baseline and weekly through acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) ADHD-RS-IV is an instrument for diagnosing ADHD in children/adolescents and for assessing treatment response. The scale contains 18 items linked directly to DSM-IV diagnostic criteria for ADHD. Parent questionnaire on home behaviors (Eng.) used in this study. Minimum score of 0 is a better outcome, maximum score of 54 is a worse outcome. |
| Change in Children's Global Assessment (CGAS) Total Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in CGAS total score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGAS is a 100-point scale measuring psychological, social, and school functioning for children aged 6 to 17 years. Minimum scores ranged from 1-10, representing the need for constant supervision (worse outcome) to maximum scores of 91-100, representing superior functioning (better outcome). |
| Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in CGI-BP mania score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe). |
| Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in CGI-BP severity depression score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4. (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe). |
| Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in CGI-BP severity depression score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe). |
| Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in CGI-BP severity overall illness score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe). |
| Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in CGI-BP severity overall illness score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe). |
| Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in CDRS-R score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CDRS-R is used to diagnose depression and monitor treatment response. The interviewer rates 17 symptom areas (including those that sever as DSM-IV criteria for diagnosis of depression), among them suicidal ideation. Minimum score on the scale is 17 (better outcome). Maximum score on the scale is 113 (worse outcome or more severe symptoms). |
| Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in GBI Total Parent/Guardian Version Mania score, using LOCF. Assessments performed at baseline and weekly through acute phase(Week 4) and Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale was completed by parent/guardian. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome. |
| Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in GBI Total Subject Version Mania score, using the LOCF. Assessments performed at baseline and weekly through acute phase (Week 4). (Also performed Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by the subject. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome. |
| Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in Y-MRS total score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 grades of severity. Minimum score on the scale is 0 (absent or normal). Maximum score on the scale is 60 (worse outcome or more severe symptoms). |
| Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 4 | Baseline and Week 4 | Change from baseline to Week 4 in GBI Total Parent/Guardian Version Depression score, using LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4); also Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale was completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome. |
| Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 30 | Baseline and Week 30 | Change from Baseline to Week 30 in GBI Total Parent/Guardian Version Depression score, using LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4); also Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome. |
| Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 4 | Baseline and Week 4 | Change from Baseline to Week 4 in GBI Total Subject Version Depression score, using LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4); also at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale was completed by subject. Symptoms wrated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome. |
| Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in GBI Total Subject Version Depression score, using LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4); also at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by the subject. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome. |
| Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in ADHD-RS-IV Total score, using the LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The ADHD-RS-IV is an instrument both for diagnosing ADHD in children and adolescents and for assessing treatment response. The scale contains 18 items and is linked directly to DSM-IV diagnostic criteria for ADHD. The parent questionnaire on home behaviors (English) was used in this study. Minimum score of 0 = better outcome, maximum score of 54 = worse outcome. |
| Subject Response to Treatment at Week 4 | Baseline and Week 4 | Percentage of Subjects with a 50% or higher reduction from baseline in Young Mania Rating Scale (Y-MRS) total score at Week 4. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 grades of severity. Minimum score on the scale is 0 (absent or normal). Maximum score on the scale is 60 (worse outcome or more severe symptoms). |
| Subject Response to Treatment at Week 30 | Baseline and Week 30 | Percentage of Subjects with a 50% or higher reduction from baseline in Y-MRS total score at Week 30. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 grades of severity. Minimum score on the scale is 0 (absent or normal). Maximum score on the scale is 60 (worse outcome or more severe symptoms). |
| Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4 | Baseline and Week 4 | Change from previous phase to Week 4 in CGI-BP mania score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse). |
| Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30 | Baseline and Week 30 | Change from previous phase to Week 30 in CGI-BP mania score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse). |
| Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4 | Baseline and Week 4 | Change from previous phase to Week 4 in CGI-BP severity depression score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse). |
| Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30 | Baseline and Week 30 | Change from previous phase to Week 30 in CGI-BP severity depression score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse). |
| Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4 | Baseline and Week 4 | Change from previous phase to Week 4 in CGI-BP severity overall illness score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse). |
| Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30 | Baseline and Week 30 | Change from previous phase to Week 30 in CGI-BP severity overall illness score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse). |
| Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 30 | Baseline and Week 30 | Change from baseline to Week 30 in GBI Total Subject Version Mania score, using LOCF. Assessments performed at baseline and weekly through acute phase (Week 4) and Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by the subject. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score of 0=better outcome, maximum score of 60=worse outcome. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 59 centers in the United States between March 2005 and February 2007. A total of 413 subjects were screened for enrollment, with 296 subjects assigned to double-blind treatment.
Pre-assignment details
Participants were screened over a 28-day period.
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole 10 mg/Day Dose was titrated to a target dose of 10 mg/day as follows: Starting dose 2 mg/day, increased to 5 mg/day on Day 3, 10 mg/day on Day 5. One dose reduction to 5 mg/day was allowed in the extension phase. Following a dose reduction, the dose could be up titrated to 10 mg/day if needed. | 98 |
| Aripiprazole 30 mg/Day Dose was titrated to a target dose of 30 mg/day as follows: Starting dose 2 mg/day, increased to 5 mg/day on Day 3, 10 mg/day on Day 5, 15 mg/day on Day 7, 20 mg/day on Day 9, 25 mg/day on Day 11, and 30 mg/day on Day 13. One dose reduction to 15 mg/day was allowed in the extension phase. Following a dose reduction, the dose could be up titrated to 20 mg/day if needed. | 99 |
| Placebo Participants were given a single pill administered once daily. | 99 |
| Total | 296 |
Baseline characteristics
| Characteristic | Total | Aripiprazole 10 mg/Day | Aripiprazole 30 mg/Day | Placebo |
|---|---|---|---|---|
| Age Continuous | 13.43 years STANDARD_DEVIATION 2.21 | 13.70 years STANDARD_DEVIATION 2.17 | 13.31 years STANDARD_DEVIATION 2.32 | 13.28 years STANDARD_DEVIATION 2.12 |
| Body Mass Index (BMI) | 23.83 kg/m^2 STANDARD_DEVIATION 5.72 | 24.15 kg/m^2 STANDARD_DEVIATION 5.37 | 23.66 kg/m^2 STANDARD_DEVIATION 6.7 | 23.68 kg/m^2 STANDARD_DEVIATION 4.98 |
| Children's Depression Rating Scale - Revised (CDRS-R) Suicidal Ideation Score | 1.2 points STANDARD_DEVIATION 0.5 | 1.1 points STANDARD_DEVIATION 0.4 | 1.1 points STANDARD_DEVIATION 0.5 | 1.2 points STANDARD_DEVIATION 0.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 6 Participants | 10 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 265 Participants | 92 Participants | 89 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 159.36 centimeters (cm) STANDARD_DEVIATION 12.12 | 161.05 centimeters (cm) STANDARD_DEVIATION 12.45 | 158.37 centimeters (cm) STANDARD_DEVIATION 12.21 | 158.69 centimeters (cm) STANDARD_DEVIATION 11.63 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 65 Participants | 24 Participants | 18 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 30 Participants | 5 Participants | 11 Participants | 14 Participants |
| Race (NIH/OMB) White | 193 Participants | 65 Participants | 68 Participants | 60 Participants |
| Sex: Female, Male Female | 137 Participants | 46 Participants | 48 Participants | 43 Participants |
| Sex: Female, Male Male | 159 Participants | 52 Participants | 51 Participants | 56 Participants |
| Treatment given for previous episodes No | 126 participants | 41 participants | 49 participants | 36 participants |
| Treatment given for previous episodes Yes | 170 participants | 57 participants | 50 participants | 63 participants |
| Weight | 61.57 kilograms (kg) STANDARD_DEVIATION 19.71 | 63.76 kilograms (kg) STANDARD_DEVIATION 20.11 | 60.49 kilograms (kg) STANDARD_DEVIATION 21.5 | 60.48 kilograms (kg) STANDARD_DEVIATION 17.31 |
| Young Mania Rating Scale Score (Y-MRS) | 30.0 points STANDARD_DEVIATION 6.5 | 29.8 points STANDARD_DEVIATION 6.5 | 29.5 points STANDARD_DEVIATION 6.3 | 30.7 points STANDARD_DEVIATION 6.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 78 / 98 | 84 / 99 | 64 / 97 |
| serious Total, serious adverse events | 5 / 98 | 7 / 99 | 6 / 97 |
Outcome results
Primary
Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 4
Change from Baseline to Week 4 in Y-MRS total score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through the continuation phase.) The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 grades of severity. Minimum score on the scale is 0 (absent or normal). Maximum score on the scale is 60 (worse outcome or more severe symptoms).
Time frame: Baseline and Week 4
Population: Since the primary efficacy endpoint is change from baseline in Y-MRS total score, only randomized subjects who had both baseline and at least one post-baseline were included in the primary efficacy analysis. Therefore, number of randomized subjects be different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 4 | -14.04 points | Standard Deviation 9.33 |
| Aripiprazole 30 mg/Day | Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 4 | -16.16 points | Standard Deviation 9.18 |
| Placebo | Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 4 | -8.67 points | Standard Deviation 9.17 |
Comparison: The change scores were analyzed by using ANCOVA model with treatment as a factor and baseline Y-MRS total score as a covariate. For comparing YMRS-Total score in treatment groups at baseline, only treatment was included in the ANOVA model with baseline values as the dependent variable. The LS means obtained from a type III analysis using SAS were used for the treatment comparisons. Two-tailed student's t-tests were used to test differences between the LS means within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-8.49, -3.5]t-test, 2 sided
Comparison: The change scores were analyzed by using ANCOVA model with treatment as a factor and baseline Y-MRS total score as a covariate. For comparing YMRS-Total score in treatment groups at baseline, only treatment was included in the ANOVA model with baseline values as the dependent variable. The LS means obtained from a type III analysis using SAS were used for the treatment comparisons. Two-tailed student's t-tests were used to test differences between the LS means within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-10.7, -5.77]t-test, 2 sided
Secondary
Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30
Change from previous phase to Week 30 in CGI-BP severity depression score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from previous week, only randomized subjects who had both previous week and at least next week were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30 | 3.3 points | Standard Deviation 1.33 |
| Aripiprazole 30 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30 | 3.06 points | Standard Deviation 1.14 |
| Placebo | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30 | 3.56 points | Standard Deviation 1.31 |
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: 0.172695% CI: [-0.64, 0.11]Cochran-Mantel-Haenszel
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: 0.011395% CI: [-0.89, -0.12]Cochran-Mantel-Haenszel
Secondary
Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4
Change from previous phase to Week 4 in CGI-BP severity depression score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline and Week 4
Population: Since the endpoint is change from previous phase, only randomized subjects who had both previous phase and at least one next phase were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4 | 2.96 points | Standard Deviation 1.27 |
| Aripiprazole 30 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4 | 3.06 points | Standard Deviation 1.26 |
| Placebo | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4 | 3.57 points | Standard Deviation 1.19 |
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: 0.00195% CI: [-0.96, -0.26]Cochran-Mantel-Haenszel
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: 0.005395% CI: [-0.85, -0.16]Cochran-Mantel-Haenszel
Secondary
Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30
Change from previous phase to Week 30 in CGI-BP mania score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from previous phase, only randomized subjects who had both previous phase and at least one next phase were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30 | 2.61 points | Standard Deviation 1.43 |
| Aripiprazole 30 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30 | 2.45 points | Standard Deviation 1.39 |
| Placebo | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30 | 3.26 points | Standard Deviation 1.35 |
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: 0.00295% CI: [-1.04, -0.24]Cochran-Mantel-Haenszel
p-value: 0.000195% CI: [-1.19, -0.41]Cochran-Mantel-Haenszel
Secondary
Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4
Change from previous phase to Week 4 in CGI-BP mania score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline and Week 4
Population: Since the endpoint is change from previous phase, only randomized subjects who had both previous phase and at least one next phase were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4 | 2.4 points | Standard Deviation 1.04 |
| Aripiprazole 30 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4 | 2.32 points | Standard Deviation 1.25 |
| Placebo | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4 | 3.37 points | Standard Deviation 1.16 |
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: <0.000195% CI: [-1.29, -0.66]Cochran-Mantel-Haenszel
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: <0.000195% CI: [-1.39, -0.7]Cochran-Mantel-Haenszel
Secondary
Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30
Change from previous phase to Week 30 in CGI-BP severity overall illness score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from previous phase, only randomized subjects who had both previous phase and at least one next phase were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30 | 2.75 points | Standard Deviation 1.49 |
| Aripiprazole 30 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30 | 2.6 points | Standard Deviation 1.38 |
| Placebo | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30 | 3.38 points | Standard Deviation 1.38 |
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: 0.000195% CI: [-1.18, -0.4]Cochran-Mantel-Haenszel
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: 0.00395% CI: [-1.04, -0.22]Cochran-Mantel-Haenszel
Secondary
Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4
Change from previous phase to Week 4 in CGI-BP severity overall illness score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the change from the preceding phase score for mania, depression, and overall bipolar illness from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline and Week 4
Population: Since the endpoint is change from previous phase, only randomized subjects who had both previous phase and at least one next phase were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4 | 2.48 points | Standard Deviation 1.09 |
| Aripiprazole 30 mg/Day | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4 | 2.41 points | Standard Deviation 1.2 |
| Placebo | Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4 | 3.47 points | Standard Deviation 1.17 |
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: <0.000195% CI: [-1.31, -0.67]Cochran-Mantel-Haenszel
Comparison: Analyzed using the Cochran-Mantel-Haenszel row mean score statistic by week.p-value: <0.000195% CI: [-1.39, -0.72]Cochran-Mantel-Haenszel
Secondary
Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 30
Change from baseline to Week 30 in ADHD-RS-IV Total score, using the LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The ADHD-RS-IV is an instrument both for diagnosing ADHD in children and adolescents and for assessing treatment response. The scale contains 18 items and is linked directly to DSM-IV diagnostic criteria for ADHD. The parent questionnaire on home behaviors (English) was used in this study. Minimum score of 0 = better outcome, maximum score of 54 = worse outcome.
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 30 | -11.04 points | Standard Deviation 19.32 |
| Aripiprazole 30 mg/Day | Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 30 | -9.76 points | Standard Deviation 13.44 |
| Placebo | Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 30 | -5.58 points | Standard Deviation 10.9 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-10.5, -3.64]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.001495% CI: [-8.94, -2.16]t-test, 2 sided
Secondary
Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 4
Change from baseline to Week 4 in ADHD-RS-IV Total score, using last observation carried forward. Assessments performed at baseline and weekly through acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) ADHD-RS-IV is an instrument for diagnosing ADHD in children/adolescents and for assessing treatment response. The scale contains 18 items linked directly to DSM-IV diagnostic criteria for ADHD. Parent questionnaire on home behaviors (Eng.) used in this study. Minimum score of 0 is a better outcome, maximum score of 54 is a worse outcome.
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 4 | -12.03 points | Standard Deviation 13.09 |
| Aripiprazole 30 mg/Day | Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 4 | -11.61 points | Standard Deviation 14.06 |
| Placebo | Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 4 | -4.57 points | Standard Deviation 9.88 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-12.3, -5.43]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-11.6, -4.83]t-test, 2 sided
Secondary
Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 30
Change from baseline to Week 30 in CDRS-R score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CDRS-R is used to diagnose depression and monitor treatment response. The interviewer rates 17 symptom areas (including those that sever as DSM-IV criteria for diagnosis of depression), among them suicidal ideation. Minimum score on the scale is 17 (better outcome). Maximum score on the scale is 113 (worse outcome or more severe symptoms).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 30 | -6.47 points | Standard Deviation 11.74 |
| Aripiprazole 30 mg/Day | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 30 | -4.39 points | Standard Deviation 10.61 |
| Placebo | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 30 | -3.81 points | Standard Deviation 10.91 |
p-value: 0.172995% CI: [-4.69, 0.85]t-test, 2 sided
p-value: 0.7558695% CI: [-3.17, 2.31]t-test, 2 sided
Secondary
Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 4
Change from baseline to Week 4 in CDRS-R score, using last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CDRS-R is used to diagnose depression and monitor treatment response. The interviewer rates 17 symptom areas (including those that sever as DSM-IV criteria for diagnosis of depression), among them suicidal ideation. Minimum score on the scale is 17 (better outcome). Maximum score on the scale is 113 (worse outcome or more severe symptoms).
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 4 | -7.65 points | Standard Deviation 11.05 |
| Aripiprazole 30 mg/Day | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 4 | -5.97 points | Standard Deviation 10.88 |
| Placebo | Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 4 | -4.66 points | Standard Deviation 9.1 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.076795% CI: [-4.81, 0.25]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.351595% CI: [-3.69, 1.32]t-test, 2 sided
Secondary
Change in Children's Global Assessment (CGAS) Total Score at Week 30
Change from baseline to Week 30 in CGAS total score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGAS is a 100-point scale measuring psychological, social, and school functioning for children aged 6 to 17 years. Minimum scores ranged from 1-10, representing the need for constant supervision (worse outcome) to maximum scores of 91-100, representing superior functioning (better outcome).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Children's Global Assessment (CGAS) Total Score at Week 30 | 15.81 points | Standard Deviation 18.81 |
| Aripiprazole 30 mg/Day | Change in Children's Global Assessment (CGAS) Total Score at Week 30 | 16.28 points | Standard Deviation 14.73 |
| Placebo | Change in Children's Global Assessment (CGAS) Total Score at Week 30 | 7.45 points | Standard Deviation 11.59 |
p-value: <0.000195% CI: [5.07, 13.93]t-test, 2 sided
p-value: <0.000195% CI: [5.87, 14.14]t-test, 2 sided
Secondary
Change in Children's Global Assessment Scale (CGAS) Total Score at Week 4
Change from baseline to Week 4 in CGAS total score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGAS is a 100-point scale measuring psychological, social, and school functioning for children aged 6 to 17 years. Minimum scores ranged from 1-10, representing the need for constant supervision (worse outcome) to maximum scores of 91-100, representing superior functioning (better outcome).
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Children's Global Assessment Scale (CGAS) Total Score at Week 4 | 14.97 points | Standard Deviation 14.94 |
| Aripiprazole 30 mg/Day | Change in Children's Global Assessment Scale (CGAS) Total Score at Week 4 | 16.96 points | Standard Deviation 13.4 |
| Placebo | Change in Children's Global Assessment Scale (CGAS) Total Score at Week 4 | 6.21 points | Standard Deviation 9.15 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [5.77, 12.84]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [7.99, 15.03]t-test, 2 sided
Secondary
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30
Change from baseline to Week 30 in CGI-BP severity depression score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30 | -0.71 points | Standard Deviation 1.44 |
| Aripiprazole 30 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30 | -0.94 points | Standard Deviation 1.38 |
| Placebo | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30 | -0.47 points | Standard Deviation 1.45 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.255395% CI: [-0.51, 0.13]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.016695% CI: [-0.71, -0.07]t-test, 2 sided
Secondary
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4
Change from baseline to Week 4 in CGI-BP severity depression score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4. (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe).
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4 | -0.86 points | Standard Deviation 1.37 |
| Aripiprazole 30 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4 | -0.9 points | Standard Deviation 1.32 |
| Placebo | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4 | -0.57 points | Standard Deviation 1.21 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.087895% CI: [-0.54, 0.04]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.075295% CI: [-0.55, 0.03]t-test, 2 sided
Secondary
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30
Change from baseline to Week 30 in CGI-BP mania score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30 | -1.63 points | Standard Deviation 1.43 |
| Aripiprazole 30 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30 | -1.93 points | Standard Deviation 1.4 |
| Placebo | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30 | -1.03 points | Standard Deviation 1.32 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.000395% CI: [-1.08, -0.33]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-1.41, -0.66]t-test, 2 sided
Secondary
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4
Change from baseline to Week 4 in CGI-BP mania score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe).
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4 | -1.6 points | Standard Deviation 1.3 |
| Aripiprazole 30 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4 | -2.02 points | Standard Deviation 1.29 |
| Placebo | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4 | -0.89 points | Standard Deviation 1.11 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-1.15, -0.48]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-1.59, -0.93]t-test, 2 sided
Secondary
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30
Change from baseline to Week 30 in CGI-BP severity overall illness score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30 | -1.59 points | Standard Deviation 1.45 |
| Aripiprazole 30 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30 | -1.75 points | Standard Deviation 1.34 |
| Placebo | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30 | -0.91 points | Standard Deviation 1.24 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-1.13, -0.4]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-1.33, -0.6]t-test, 2 sided
Secondary
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4
Change from baseline to Week 4 in CGI-BP severity overall illness score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The CGI-BP scale refers to the global impression of the subject with respect to bipolar disorder. The scale rates the subject's severity of illness for mania, depression, and overall bipolar illness from 1 (least severe) to 7 (most severe).
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4 | -1.6 points | Standard Deviation 1.33 |
| Aripiprazole 30 mg/Day | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4 | -1.91 points | Standard Deviation 1.21 |
| Placebo | Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4 | -0.84 points | Standard Deviation 1.02 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-1.16, -0.51]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-1.51, -0.86]t-test, 2 sided
Secondary
Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 30
Change from Baseline to Week 30 in GBI Total Parent/Guardian Version Depression score, using LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4); also Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 30 | -5.17 points | Standard Deviation 9.13 |
| Aripiprazole 30 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 30 | -3.71 points | Standard Deviation 9 |
| Placebo | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 30 | -3.03 points | Standard Deviation 9.27 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.941895% CI: [-1.73, 1.86]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.1995% CI: [-1.67, 1.98]t-test, 2 sided
Secondary
Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 4
Change from baseline to Week 4 in GBI Total Parent/Guardian Version Depression score, using LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4); also Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale was completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 4 | -6.12 points | Standard Deviation 8.78 |
| Aripiprazole 30 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 4 | -3.71 points | Standard Deviation 8.62 |
| Placebo | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 4 | -3.92 points | Standard Deviation 8.82 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.04395% CI: [-4.2, -0.07]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.769695% CI: [-2.37, 1.76]t-test, 2 sided
Secondary
Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 30
Change from baseline to Week 30 in GBI Total Parent/Guardian Version Mania score, using LOCF. Assessments performed at baseline and weekly through acute phase(Week 4) and Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale was completed by parent/guardian. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 30 | -8.76 points | Standard Deviation 9.12 |
| Aripiprazole 30 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 30 | -8.48 points | Standard Deviation 8.44 |
| Placebo | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 30 | -5 points | Standard Deviation 9.33 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-6.9, -2.61]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-6.78, -2.5]t-test, 2 sided
Secondary
Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 4
Change from baseline to Week 4 in GBI Total Parent/Guardian Version Mania score, using LOCF. Assessments performed baseline and weekly through acute phase (Week 4). (Also at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) GBI is self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale was completed by parent/guardian. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 4 | -9.66 points | Standard Deviation 9.14 |
| Aripiprazole 30 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 4 | -9.1 points | Standard Deviation 7.91 |
| Placebo | Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 4 | -4.63 points | Standard Deviation 8.97 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-8.02, -3.73]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-7.4, -3.32]t-test, 2 sided
Secondary
Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 30
Change from baseline to Week 30 in GBI Total Subject Version Depression score, using LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4); also at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by the subject. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 30 | -4.45 points | Standard Deviation 7.62 |
| Aripiprazole 30 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 30 | -4.38 points | Standard Deviation 8.09 |
| Placebo | Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 30 | -2.7 points | Standard Deviation 8.44 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.396995% CI: [-2.71, 1.08]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.210195% CI: [-3.09, 0.68]t-test, 2 sided
Secondary
Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 4
Change from Baseline to Week 4 in GBI Total Subject Version Depression score, using LOCF. Assessments performed at baseline and weekly through the acute phase (Week 4); also at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale was completed by subject. Symptoms wrated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 4 | 0 points | Standard Deviation 6.87 |
| Aripiprazole 30 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 4 | -3.24 points | Standard Deviation 6.96 |
| Placebo | Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 4 | -3.11 points | Standard Deviation 7.73 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.941895% CI: [-1.73, 1.86]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.837795% CI: [-1.61, 1.98]t-test, 2 sided
Secondary
Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 30
Change from baseline to Week 30 in GBI Total Subject Version Mania score, using LOCF. Assessments performed at baseline and weekly through acute phase (Week 4) and Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by the subject. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score of 0=better outcome, maximum score of 60=worse outcome.
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 30 | -6.82 points | Standard Deviation 7.86 |
| Aripiprazole 30 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 30 | -7.84 points | Standard Deviation 7.7 |
| Placebo | Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 30 | -5.23 points | Standard Deviation 7.68 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.130995% CI: [-3.31, 0.43]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.005895% CI: [-4.51, -0.77]t-test, 2 sided
Secondary
Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 4
Change from baseline to Week 4 in GBI Total Subject Version Mania score, using the LOCF. Assessments performed at baseline and weekly through acute phase (Week 4). (Also performed Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by the subject. Symptoms rated on a 4-point Likert scale from 0 (never or hardly ever) to 3 (often or almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time frame: Baseline and Week 4
Population: Since the endpoint is change from baseline, only randomized subjects who had both baseline and at least one post-baseline were included in the efficacy analysis. Therefore, number of randomized subjects could be a different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 4 | -6.51 points | Standard Deviation 7.49 |
| Aripiprazole 30 mg/Day | Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 4 | -6.52 points | Standard Deviation 7.49 |
| Placebo | Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 4 | -4.57 points | Standard Deviation 7.21 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.046895% CI: [-3.67, -0.03]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor, and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: 0.029695% CI: [-3.85, -0.2]t-test, 2 sided
Secondary
Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 30
Change from baseline to Week 30 in Y-MRS total score, using the last observation carried forward. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 grades of severity. Minimum score on the scale is 0 (absent or normal). Maximum score on the scale is 60 (worse outcome or more severe symptoms).
Time frame: Baseline and Week 30
Population: Since the endpoint is change from baseline in Y-MRS total score, only randomized subjects who had both baseline and at least one post-baseline were included in the primary efficacy analysis. Therefore, number of randomized subjects could be different number subjects included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day | Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 30 | -13.91 points | Standard Deviation 10.83 |
| Aripiprazole 30 mg/Day | Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 30 | -14.6 points | Standard Deviation 10.35 |
| Placebo | Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 30 | -8.69 points | Standard Deviation 9.88 |
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [-8.7, -3.08]t-test, 2 sided
Comparison: Analyses were performed by fitting an ANCOVA model with treatment as factor and baseline score as covariate. Two pair-wise comparisons, aripiprazole 10 mg target dose versus placebo and aripiprazole 30 mg target dose versus placebo, were performed within the ANCOVA or ANOVA model.p-value: <0.000195% CI: [7.99, 15.03]t-test, 2 sided
Secondary
Subject Response to Treatment at Week 30
Percentage of Subjects with a 50% or higher reduction from baseline in Y-MRS total score at Week 30. Assessments performed at baseline and weekly through the acute phase (Week 4) and at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase. The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 grades of severity. Minimum score on the scale is 0 (absent or normal). Maximum score on the scale is 60 (worse outcome or more severe symptoms).
Time frame: Baseline and Week 30
Population: Since the primary efficacy endpoint is change from baseline in Y-MRS total score, only randomized subjects who had both baseline and at least one post-baseline were included in the primary efficacy analysis. Therefore, number of randomized subjects could be different number subjects included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aripiprazole 10 mg/Day | Subject Response to Treatment at Week 30 | 50.00 percentage of participants |
| Aripiprazole 30 mg/Day | Subject Response to Treatment at Week 30 | 55.56 percentage of participants |
| Placebo | Subject Response to Treatment at Week 30 | 26.60 percentage of participants |
Comparison: Analyzed using a Chi-square test. Ninety five percent confidence intervals for difference in the responder rates are derived from the normal approximation to binomial.p-value: 0.000995% CI: [9.57, 37.24]Chi-squared
Comparison: Analyzed using a Chi-square test. Ninety five percent confidence intervals for difference in the responder rates are derived from the normal approximation to binomial.p-value: <0.000195% CI: [15.05, 42.87]Chi-squared
Secondary
Subject Response to Treatment at Week 4
Percentage of Subjects with a 50% or higher reduction from baseline in Young Mania Rating Scale (Y-MRS) total score at Week 4. Assessments performed at baseline and weekly through the acute phase (Week 4). (Also performed at Weeks 6, 8, 10, 12, 16, 20, 24, and 30 through continuation phase.) The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 grades of severity. Minimum score on the scale is 0 (absent or normal). Maximum score on the scale is 60 (worse outcome or more severe symptoms).
Time frame: Baseline and Week 4
Population: Since the primary efficacy endpoint is change from baseline in Y-MRS total score, only randomized subjects who had both baseline and at least one post-baseline were included in the primary efficacy analysis. Therefore, number of randomized subjects could be different number subjects included in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aripiprazole 10 mg/Day | Subject Response to Treatment at Week 4 | 44.79 percentage of participants |
| Aripiprazole 30 mg/Day | Subject Response to Treatment at Week 4 | 63.64 percentage of participants |
| Placebo | Subject Response to Treatment at Week 4 | 26.09 percentage of participants |
Comparison: Analyzed using a Chi-square test. Ninety five percent confidence intervals for difference in the responder rates are derived from the normal approximation to binomial.p-value: 0.007495% CI: [5.01, 32.4]Chi-squared
Comparison: Analyzed using a Chi-square test. Ninety five percent confidence intervals for difference in the responder rates are derived from the normal approximation to binomial.p-value: <0.000195% CI: [23.41, 51.68]Chi-squared