Aripiprazole in Children and Adolescents With Bipolar I Disorder

Bipolar Disorder Clinical Trial

Official title:

A Phase III Trial 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00110461
• Other study ID #: 31-03-240
• Status: Completed
• Phase: Phase 3
• First received: May 9, 2005
• Last updated: April 19, 2012
• Start date: March 2005
• Est. completion date: February 2007

Study information

• Verified date: April 2012
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 296
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 17 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Aripiprazole
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.
• Aripiprazole
Treatment Arm 2 (30 mg treatment arm): Aripiprazole 2 mg QD for 2 days, aripiprazole 5 mg QD for 2 days, aripiprazole 10 mg QD for 2 days, aripiprazole 15 mg QD for 2 days, aripiprazole 20 mg QD for 2 days, aripiprazole 25 mg QD for 2 days, and aripiprazole 30 mg QD as the target dose starting on Day 13. Subjects remained on the 30 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.
• placebo
Placebo tablet

Locations

Country	Name	City	State
United States	Local Institution	Altamonte Springs	Florida
United States	Local Institution	Atlanta	Georgia
United States	Local Institution	Baton Rouge	Louisiana
United States	Local Institution	Bellaire	Texas
United States	Local Institution	Boise	Idaho
United States	Local Institution	Cambridge	Massachusetts
United States	Local Institution	Charleston	South Carolina
United States	Local Institution	Chicago	Illinois
United States	Local Institution	Cincinnati	Ohio
United States	Local Institution	Cleveland	Ohio
United States	Local Institution	Clinton Township	Michigan
United States	Local Institution	Elmsford	New York
United States	Local Institution	Fort Worth	Texas
United States	Local Institution	Herndon	Virginia
United States	Local Institution	Hialeah	Florida
United States	Local Institution	Houston	Texas
United States	Local Institution	Indianapolis	Indiana
United States	Local Institution	Jacksonville	Florida
United States	Local Institution	Kansas City	Kansas
United States	Local Institution	Kansas City	Missouri
United States	Local Institution	Kirkland	Washington
United States	Local Institution	Lake Charles	Louisiana
United States	Local Institution	Las Vegas	Nevada
United States	Local Institution	Lexington	Kentucky
United States	Local Institution	Libertyville	Illinois
United States	Local Institution	Little Rock	Arkansas
United States	Local Institution	Medford	Massachusetts
United States	Local Institution	Memphis	Tennessee
United States	Local Institution	Miami	Florida
United States	Local Institution	Milwaukee	Wisconsin
United States	Local Institution	National City	California
United States	Local Institution	New York City	New York
United States	Local Institution	Newton	Kansas
United States	Local Institution	North Miami	Florida
United States	Local Institution	Oklahoma City	Oklahoma
United States	Local Institution	Orange	California
United States	Local Institution	Pasadena	California
United States	Local Institution	Philadelphia	Pennsylvania
United States	Local Institution	Richmond	Virginia
United States	Local Institution	Rochester	New York
United States	Local Institution	Rochester Hills	Michigan
United States	Local Institution	Sacramento	California
United States	Local Institution	San Antonio	Texas
United States	Local Institution	San Diego	California
United States	Local Institution	Scottsdale	Arizona
United States	Local Institution	Shreveport	Louisiana
United States	Local Institution	Smyrna	Georgia
United States	Local Institution	Spokane	Washington
United States	Local Institution	St. Louis	Missouri
United States	Local Institution	Stanford	California
United States	Local Institution	Stony Brook	New York
United States	Local Institution	Tampa	Florida
United States	Local Institution	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	Baseline and Week 4	No
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).	Baseline and Week 30	No
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).	Baseline and Week 4	No
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).	Baseline and Week 4	No
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).	Baseline and Week 4	No
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.	Baseline and Week 4	No
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.	Baseline and Week 4	No
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).	Baseline and Week 30	No
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).	Baseline and Week 30	No
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).	Baseline and Week 4	No
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).	Baseline and Week 30	No
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).	Baseline and Week 4	No
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).	Baseline and Week 30	No
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).	Baseline and Week 30	No
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.	Baseline and Week 30	No
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.	Baseline and Week 4	No
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.	Baseline and Week 30	No
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.	Baseline and Week 4	No
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.	Baseline and Week 30	No
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.	Baseline and Week 4	No
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.	Baseline and Week 30	No
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.	Baseline and Week 30	No
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).	Baseline and Week 4	No
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).	Baseline and Week 30	No
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).	Baseline and Week 4	No
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).	Baseline and Week 30	No
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).	Baseline and Week 4	No
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).	Baseline and Week 30	No
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).	Baseline and Week 4	No
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).	Baseline and Week 30	No