Trial Outcomes & Findings for Aripiprazole in Children and Adolescents With Bipolar I Disorder (NCT NCT00110461)

NCT ID: NCT00110461

Last Updated: 2012-05-21

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

296 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2012-05-21

Participant Flow

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.

Participants were screened over a 28-day period.

Participant milestones

Participant milestones
Measure
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.
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.
Placebo
Participants were given a single pill administered once daily.
30-Week, Double-blind Treatment Phase
STARTED
98
99
99
30-Week, Double-blind Treatment Phase
COMPLETED
34
22
12
30-Week, Double-blind Treatment Phase
NOT COMPLETED
64
77
87
Acute Phase
STARTED
98
99
99
Acute Phase
COMPLETED
84
77
76
Acute Phase
NOT COMPLETED
14
22
23

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Aripiprazole in Children and Adolescents With Bipolar I Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Aripiprazole 10 mg/Day
n=98 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=99 Participants
Participants were given a single pill administered once daily.
Total
n=296 Participants
Total of all reporting groups
Age Continuous
13.70 years
STANDARD_DEVIATION 2.17 • n=5 Participants
13.31 years
STANDARD_DEVIATION 2.32 • n=7 Participants
13.28 years
STANDARD_DEVIATION 2.12 • n=5 Participants
13.43 years
STANDARD_DEVIATION 2.21 • n=4 Participants
Sex: Female, Male
Female
46 Participants
n=5 Participants
48 Participants
n=7 Participants
43 Participants
n=5 Participants
137 Participants
n=4 Participants
Sex: Female, Male
Male
52 Participants
n=5 Participants
51 Participants
n=7 Participants
56 Participants
n=5 Participants
159 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants
n=5 Participants
10 Participants
n=7 Participants
15 Participants
n=5 Participants
31 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
92 Participants
n=5 Participants
89 Participants
n=7 Participants
84 Participants
n=5 Participants
265 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
2 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
2 Participants
n=4 Participants
Race (NIH/OMB)
Black or African American
24 Participants
n=5 Participants
18 Participants
n=7 Participants
23 Participants
n=5 Participants
65 Participants
n=4 Participants
Race (NIH/OMB)
White
65 Participants
n=5 Participants
68 Participants
n=7 Participants
60 Participants
n=5 Participants
193 Participants
n=4 Participants
Race (NIH/OMB)
More than one race
2 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
6 Participants
n=4 Participants
Race (NIH/OMB)
Unknown or Not Reported
5 Participants
n=5 Participants
11 Participants
n=7 Participants
14 Participants
n=5 Participants
30 Participants
n=4 Participants
Height
161.05 centimeters (cm)
STANDARD_DEVIATION 12.45 • n=5 Participants
158.37 centimeters (cm)
STANDARD_DEVIATION 12.21 • n=7 Participants
158.69 centimeters (cm)
STANDARD_DEVIATION 11.63 • n=5 Participants
159.36 centimeters (cm)
STANDARD_DEVIATION 12.12 • n=4 Participants
Weight
63.76 kilograms (kg)
STANDARD_DEVIATION 20.11 • n=5 Participants
60.49 kilograms (kg)
STANDARD_DEVIATION 21.50 • n=7 Participants
60.48 kilograms (kg)
STANDARD_DEVIATION 17.31 • n=5 Participants
61.57 kilograms (kg)
STANDARD_DEVIATION 19.71 • n=4 Participants
Body Mass Index (BMI)
24.15 kg/m^2
STANDARD_DEVIATION 5.37 • n=5 Participants
23.66 kg/m^2
STANDARD_DEVIATION 6.70 • n=7 Participants
23.68 kg/m^2
STANDARD_DEVIATION 4.98 • n=5 Participants
23.83 kg/m^2
STANDARD_DEVIATION 5.72 • n=4 Participants
Young Mania Rating Scale Score (Y-MRS)
29.8 points
STANDARD_DEVIATION 6.5 • n=5 Participants
29.5 points
STANDARD_DEVIATION 6.3 • n=7 Participants
30.7 points
STANDARD_DEVIATION 6.8 • n=5 Participants
30.0 points
STANDARD_DEVIATION 6.5 • n=4 Participants
Children's Depression Rating Scale - Revised (CDRS-R) Suicidal Ideation Score
1.1 points
STANDARD_DEVIATION 0.4 • n=5 Participants
1.1 points
STANDARD_DEVIATION 0.5 • n=7 Participants
1.2 points
STANDARD_DEVIATION 0.5 • n=5 Participants
1.2 points
STANDARD_DEVIATION 0.5 • n=4 Participants
Treatment given for previous episodes
Yes
57 participants
n=5 Participants
50 participants
n=7 Participants
63 participants
n=5 Participants
170 participants
n=4 Participants
Treatment given for previous episodes
No
41 participants
n=5 Participants
49 participants
n=7 Participants
36 participants
n=5 Participants
126 participants
n=4 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 4
-14.04 points
Standard Deviation 9.33 • Interval -8.49 to -3.5
-16.16 points
Standard Deviation 9.18 • Interval -10.7 to -5.77
-8.67 points
Standard Deviation 9.17

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 30
-13.91 points
Standard Deviation 10.83
-14.6 points
Standard Deviation 10.35
-8.69 points
Standard Deviation 9.88

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
Change in Children's Global Assessment Scale (CGAS) Total Score at Week 4
14.97 points
Standard Deviation 14.94
16.96 points
Standard Deviation 13.4
6.21 points
Standard Deviation 9.15

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4
-1.6 points
Standard Deviation 1.3
-2.02 points
Standard Deviation 1.29
-0.89 points
Standard Deviation 1.11

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=91 Participants
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.
Aripiprazole 30 mg/Day
n=94 Participants
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.
Placebo
n=85 Participants
Participants were given a single pill administered once daily.
Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 4
-7.65 points
Standard Deviation 11.05
-5.97 points
Standard Deviation 10.88
-4.66 points
Standard Deviation 9.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=96 Participants
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.
Placebo
n=91 Participants
Participants were given a single pill administered once daily.
Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 4
-9.66 points
Standard Deviation 9.14
-9.1 points
Standard Deviation 7.91
-4.63 points
Standard Deviation 8.97

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=95 Participants
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.
Aripiprazole 30 mg/Day
n=97 Participants
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.
Placebo
n=90 Participants
Participants were given a single pill administered once daily.
Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 4
-12.03 points
Standard Deviation 13.09
-11.61 points
Standard Deviation 14.06
-4.57 points
Standard Deviation 9.88

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
Change in Children's Global Assessment (CGAS) Total Score at Week 30
15.81 points
Standard Deviation 18.81
16.28 points
Standard Deviation 14.73
7.45 points
Standard Deviation 11.59

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30
-1.63 points
Standard Deviation 1.43
-1.93 points
Standard Deviation 1.4
-1.03 points
Standard Deviation 1.32

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4
-0.86 points
Standard Deviation 1.37
-0.9 points
Standard Deviation 1.32
-0.57 points
Standard Deviation 1.21

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30
-0.71 points
Standard Deviation 1.44
-0.94 points
Standard Deviation 1.38
-0.47 points
Standard Deviation 1.45

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4
-1.6 points
Standard Deviation 1.33
-1.91 points
Standard Deviation 1.21
-0.84 points
Standard Deviation 1.02

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30
-1.59 points
Standard Deviation 1.45
-1.75 points
Standard Deviation 1.34
-0.91 points
Standard Deviation 1.24

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=91 Participants
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.
Aripiprazole 30 mg/Day
n=94 Participants
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.
Placebo
n=86 Participants
Participants were given a single pill administered once daily.
Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 30
-6.47 points
Standard Deviation 11.74
-4.39 points
Standard Deviation 10.61
-3.81 points
Standard Deviation 10.91

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=95 Participants
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.
Aripiprazole 30 mg/Day
n=96 Participants
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.
Placebo
n=93 Participants
Participants were given a single pill administered once daily.
Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 30
-8.76 points
Standard Deviation 9.12
-8.48 points
Standard Deviation 8.44
-5 points
Standard Deviation 9.33

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=96 Participants
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.
Placebo
n=91 Participants
Participants were given a single pill administered once daily.
Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 4
-6.51 points
Standard Deviation 7.49
-6.52 points
Standard Deviation 7.49
-4.57 points
Standard Deviation 7.21

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=96 Participants
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.
Placebo
n=93 Participants
Participants were given a single pill administered once daily.
Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 30
-6.82 points
Standard Deviation 7.86
-7.84 points
Standard Deviation 7.7
-5.23 points
Standard Deviation 7.68

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=95 Participants
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.
Aripiprazole 30 mg/Day
n=96 Participants
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.
Placebo
n=91 Participants
Participants were given a single pill administered once daily.
Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 4
-6.12 points
Standard Deviation 8.78
-3.71 points
Standard Deviation 8.62
-3.92 points
Standard Deviation 8.82

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=96 Participants
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.
Placebo
n=91 Participants
Participants were given a single pill administered once daily.
Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 30
-5.17 points
Standard Deviation 9.13
-3.71 points
Standard Deviation 9
-3.03 points
Standard Deviation 9.27

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=96 Participants
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.
Placebo
n=91 Participants
Participants were given a single pill administered once daily.
Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 4
0 points
Standard Deviation 6.87
-3.24 points
Standard Deviation 6.96
-3.11 points
Standard Deviation 7.73

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=96 Participants
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.
Placebo
n=93 Participants
Participants were given a single pill administered once daily.
Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 30
-4.45 points
Standard Deviation 7.62
-4.38 points
Standard Deviation 8.09
-2.7 points
Standard Deviation 8.44

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=95 Participants
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.
Aripiprazole 30 mg/Day
n=97 Participants
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.
Placebo
n=91 Participants
Participants were given a single pill administered once daily.
Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 30
-11.04 points
Standard Deviation 19.32
-9.76 points
Standard Deviation 13.44
-5.58 points
Standard Deviation 10.9

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
Subject Response to Treatment at Week 4
44.79 percentage of participants
63.64 percentage of participants
26.09 percentage of participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
Subject Response to Treatment at Week 30
50.00 percentage of participants
55.56 percentage of participants
26.60 percentage of participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
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
2.32 points
Standard Deviation 1.25
3.37 points
Standard Deviation 1.16

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
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
2.45 points
Standard Deviation 1.39
3.26 points
Standard Deviation 1.35

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
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
3.06 points
Standard Deviation 1.26
3.57 points
Standard Deviation 1.19

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
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
3.06 points
Standard Deviation 1.14
3.56 points
Standard Deviation 1.31

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=92 Participants
Participants were given a single pill administered once daily.
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
2.41 points
Standard Deviation 1.2
3.47 points
Standard Deviation 1.17

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure
Aripiprazole 10 mg/Day
n=96 Participants
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.
Aripiprazole 30 mg/Day
n=99 Participants
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.
Placebo
n=94 Participants
Participants were given a single pill administered once daily.
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
2.6 points
Standard Deviation 1.38
3.38 points
Standard Deviation 1.38

Adverse Events

Aripiprazole 10 mg/Day

Serious events: 5 serious events
Other events: 78 other events
Deaths: 0 deaths

Aripiprazole 30 mg/Day

Serious events: 7 serious events
Other events: 84 other events
Deaths: 0 deaths

Placebo

Serious events: 6 serious events
Other events: 64 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Aripiprazole 10 mg/Day
n=98 participants at risk
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.
Aripiprazole 30 mg/Day
n=99 participants at risk
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.
Placebo
n=97 participants at risk
Participants were given a single pill administered once daily.
General disorders
Fatigue
1.0%
1/98
0.00%
0/99
0.00%
0/97
Injury, poisoning and procedural complications
Accidental overdose
1.0%
1/98
0.00%
0/99
0.00%
0/97
Nervous system disorders
Grand mal convulsion
1.0%
1/98
0.00%
0/99
0.00%
0/97
Psychiatric disorders
Agression
2.0%
2/98
0.00%
0/99
0.00%
0/97
Psychiatric disorders
Bipolar disorder
0.00%
0/98
5.1%
5/99
4.1%
4/97
Psychiatric disorders
Bipolar I disorder
0.00%
0/98
2.0%
2/99
1.0%
1/97
Psychiatric disorders
Libido increased
0.00%
0/98
1.0%
1/99
0.00%
0/97
Psychiatric disorders
Mania
0.00%
0/98
0.00%
0/99
1.0%
1/97
Psychiatric disorders
Oppositional defiant disorder
1.0%
1/98
0.00%
0/99
0.00%
0/97
Psychiatric disorders
Suicidal ideation
1.0%
1/98
0.00%
0/99
0.00%
0/97
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
1.0%
1/98
0.00%
0/99
0.00%
0/97

Other adverse events

Other adverse events
Measure
Aripiprazole 10 mg/Day
n=98 participants at risk
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.
Aripiprazole 30 mg/Day
n=99 participants at risk
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.
Placebo
n=97 participants at risk
Participants were given a single pill administered once daily.
Eye disorders
Vision blurred
10.2%
10/98
8.1%
8/99
1.0%
1/97
Gastrointestinal disorders
Abdominal pain
9.2%
9/98
5.1%
5/99
3.1%
3/97
Gastrointestinal disorders
Diarrhea
4.1%
4/98
5.1%
5/99
0.00%
0/97
Gastrointestinal disorders
Nausea
13.3%
13/98
14.1%
14/99
5.2%
5/97
Gastrointestinal disorders
Salivary hypersecretion
3.1%
3/98
8.1%
8/99
0.00%
0/97
Gastrointestinal disorders
Stomach discomfort
2.0%
2/98
6.1%
6/99
2.1%
2/97
Gastrointestinal disorders
Vomiting
13.3%
13/98
8.1%
8/99
9.3%
9/97
General disorders
Fatigue
18.4%
18/98
12.1%
12/99
4.1%
4/97
Infections and infestations
Nasopharyngitis
7.1%
7/98
3.0%
3/99
3.1%
3/97
Infections and infestations
Upper respiratory tract infection
8.2%
8/98
6.1%
6/99
3.1%
3/97
Investigations
Weight increased
8.2%
8/98
5.1%
5/99
3.1%
3/97
Metabolism and nutrition disorders
Decreased appetite
7.1%
7/98
4.0%
4/99
3.1%
3/97
Metabolism and nutrition disorders
Increased appetite
8.2%
8/98
8.1%
8/99
3.1%
3/97
Musculoskeletal and connective tissue disorders
Back pain
5.1%
5/98
3.0%
3/99
2.1%
2/97
Nervous system disorders
Akathisia
9.2%
9/98
13.1%
13/99
2.1%
2/97
Nervous system disorders
Dizziness
7.1%
7/98
5.1%
5/99
1.0%
1/97
Nervous system disorders
Dystonia
2.0%
2/98
5.1%
5/99
0.00%
0/97
Nervous system disorders
Extrapyramidal disorder
12.2%
12/98
28.3%
28/99
3.1%
3/97
Nervous system disorders
Headache
20.4%
20/98
23.2%
23/99
18.6%
18/97
Nervous system disorders
Somnolence
24.5%
24/98
27.3%
27/99
3.1%
3/97
Psychiatric disorders
Anxiety, upper
5.1%
5/98
1.0%
1/99
3.1%
3/97
Psychiatric disorders
Bipolar disorder
0.00%
0/98
6.1%
6/99
5.2%
5/97
Psychiatric disorders
Insomnia
6.1%
6/98
1.0%
1/99
2.1%
2/97
Reproductive system and breast disorders
Dysmenorrhea
5.1%
5/98
0.00%
0/99
2.1%
2/97
Respiratory, thoracic and mediastinal disorders
Cough, upper
7.1%
7/98
1.0%
1/99
4.1%
4/97
Respiratory, thoracic and mediastinal disorders
Nasal congestion
10.2%
10/98
3.0%
3/99
3.1%
3/97
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
5.1%
5/98
2.0%
2/99
3.1%
3/97

Additional Information

Andy Forbes

Otsuka Pharmaceutical Development & Commercialization, Inc.

Results disclosure agreements

  • Principal investigator is a sponsor employee PIs may not publish trial results for 18 months - 2 years after trial is completed.
  • Publication restrictions are in place

Restriction type: OTHER