Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of Aripiprazole (Abilify) in Patients With Bipolar Mania

This study has been completed.
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00261443
First received: December 1, 2005
Last updated: November 7, 2013
Last verified: April 2011
Results First Received: January 28, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Bipolar Disorder
Interventions: Drug: Lithium or Valproate with placebo (PBO)
Drug: Lithium or Valproate with Aripiprazole

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Pre-Randomized Participants Phase 1 (2 to 8 Week Screening, Washout and Confirmation of Partial Nonresponse Phase): lithium: 0.6–1.0 mmol/L or valproate 50–125 µg/ml. Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6–1.0 mmol/L or valproate 50–125 µg/ml.
Placebo Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and lithium: 0.6–1.0 mmol/L or valproate 50–125 µg/ml.
Aripiprazole Phase 3 (52 Week Assessment of Relapse Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6–1.0 mmol/L or valproate 50–125 µg/ml.

Participant Flow for 4 periods

Period 1:   1: Confirmation of Partial Nonresponse
    Pre-Randomized Participants     Placebo     Aripiprazole  
STARTED     1270     0     0  
COMPLETED     686     0     0  
NOT COMPLETED     584     0     0  
Adverse Event                 33                 0                 0  
Withdrawal by Subject                 93                 0                 0  
Lost to Follow-up                 111                 0                 0  
Poor/Noncompliance                 23                 0                 0  
Pregnancy                 1                 0                 0  
Subject No Longer Met Study Criteria                 307                 0                 0  
Other Reasons                 16                 0                 0  

Period 2:   2: Stability & Maintenance of Stability
    Pre-Randomized Participants     Placebo     Aripiprazole  
STARTED     686     0     0  
COMPLETED     346     0     0  
NOT COMPLETED     340     0     0  
Lack of Efficacy                 43                 0                 0  
Adverse Event                 93                 0                 0  
Withdrawal by Subject                 65                 0                 0  
Lost to Follow-up                 59                 0                 0  
Poor/Noncompliance                 33                 0                 0  
Pregnancy                 1                 0                 0  
subject No Longer Met Study Criteria                 32                 0                 0  
Administrative Reason by Sponsor                 1                 0                 0  
Other Reasons                 13                 0                 0  

Period 3:   3: Assessment of Relapse
    Pre-Randomized Participants     Placebo     Aripiprazole  
STARTED     0     169     168  
COMPLETED     0     89     103  
NOT COMPLETED     0     80     65  
Lack of Efficacy                 0                 31                 14  
Adverse Event                 0                 15                 19  
Withdrawal by Subject                 0                 14                 15  
Death                 0                 0                 1  
Lost to Follow-up                 0                 7                 6  
Poor/Noncompliance                 0                 5                 3  
Pregnancy                 0                 2                 1  
Subject No Longer Meets Study Criteria                 0                 2                 1  
Administrative Reason By Sponsor                 0                 0                 2  
Other Reasons                 0                 4                 3  

Period 4:   4: Extension Phase
    Pre-Randomized Participants     Placebo     Aripiprazole  
STARTED     0     19     23  
COMPLETED     0     16     21  
NOT COMPLETED     0     3     2  
Adverse Event                 0                 1                 0  
Withdrawal by Subject                 0                 1                 2  
Lost to Follow-up                 0                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Placebo Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
Aripiprazole Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
Total Total of all reporting groups

Baseline Measures
    Placebo     Aripiprazole     Total  
Number of Participants  
[units: participants]
  169     168     337  
Age  
[units: years]
Mean ± Standard Deviation
  38.8  ± 12.29     39.2  ± 12.43     39.0  ± 12.34  
Gender  
[units: participants]
     
Female     98     87     185  
Male     71     81     152  
Race/Ethnicity, Customized  
[units: participants]
     
White     112     118     230  
Black/African American     19     12     31  
Asian     33     34     67  
Other     5     4     9  
Race/Ethnicity, Customized  
[units: Participants]
     
Hispanic/Latino     3     5     8  
Not Hispanic or Latino     55     56     111  
Non-US     111     107     218  
Region of Enrollment  
[units: participants]
     
France     8     9     17  
United States     58     61     119  
Czech Republic     18     14     32  
Brazil     28     27     55  
Croatia     3     4     7  
Russian Federation     17     15     32  
South Africa     4     4     8  
India     33     34     67  
Body Mass Index (BMI) Category [1]
[units: Participants]
     
<18.5 kg/m^2     5     0     5  
18.5 kg/m^2 to <25 kg/m^2     58     49     107  
25 kg/m^2 to <30 kg/m^2     50     63     113  
>= 30 kg/m^2     56     56     112  
Body Mass Index (BMI) [1]
[units: kg/m^2]
Mean ± Standard Deviation
  28.7  ± 7.72     28.5  ± 6.00     28.6  ± 6.90  
CGI-BP Change from Preceding Phase Score (Depression) [2]
[units: units on a scale]
Mean ± Standard Deviation
  3.0  ± 1.34     3.0  ± 1.31     3.0  ± 1.32  
CGI-BP Change from Preceding Phase Score (Mania) [2]
[units: units on a scale]
Mean ± Standard Deviation
  1.6  ± 0.81     1.4  ± 0.63     1.5  ± 0.72  
CGI-BP Change from Preceding Phase Score (Overall) [2]
[units: units on a scale]
Mean ± Standard Deviation
  1.6  ± 0.85     1.5  ± 0.69     1.6  ± 0.77  
CGI-BP Severity of Illness Score (Depression) [3]
[units: units on a scale]
Mean ± Standard Deviation
  1.3  ± 0.57     1.4  ± 0.70     1.4  ± 0.64  
CGI-BP Severity of Illness Score (Mania) [3]
[units: units on a scale]
Mean ± Standard Deviation
  1.5  ± 0.72     1.5  ± 0.72     1.5  ± 0.72  
CGI-BP Severity of Illness Score (Overall) [3]
[units: units on a scale]
Mean ± Standard Deviation
  1.6  ± 0.76     1.7  ± 0.83     1.6  ± 0.79  
Montgomery Åsberg Depression Rating Scale (MADRS) Total Score [4]
[units: units on a scale]
Mean ± Standard Deviation
  3.7  ± 3.45     4.1  ± 3.82     3.9  ± 3.64  
Weight  
[units: kg]
Mean ± Standard Deviation
  81.3  ± 25.11     80.6  ± 18.89     81.0  ± 22.20  
Young-Mania Rating Scale (Y-MRS) Total Score [5]
[units: units on a scale]
Mean ± Standard Deviation
  4.1  ± 3.31     4.1  ± 3.56     4.1  ± 3.43  
[1] BMI is defined as weight in kilograms divided by the square of height in meters.
[2] Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale (1 to 7), with 1 being very much improved and 7 being very much worse).
[3] Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Severity of Illness (mania, depression, and overall bipolar illness) items (a 7-point scale from 1 to 7, with 1 being normal, not ill and 7 being very severely ill).
[4] MADRS consists of 10-items, ordinal rating scale The possible total scores are from 0 to 60 (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
[5] The Y-MRS consists of 11 items: 1) Elevated Mood, 2) Increased Motor Activity -Energy, 3) Sexual Interest, 4) Sleep, 5) Irritability, 6) Speech (Rate and Amount), 7) Language -Thought Disorder, 8) Content, 9) Disruptive-Aggressive Behavior, 10) Appearance, 11) Insight. Seven items are rated on a 0 to 4 scale, while 4 items (items 5, 6, 8 and 9) are rated on a 0 to 8 scale (twice the weight of the other items.) For all items, 0 is the “best” rating and 4 or 8 is the “worst” rating. Total Score is the sum of the ratings for all 11 items. The possible Total Scores are from 0 to 60.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3   [ Time Frame: Week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

2.  Secondary:   Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3   [ Time Frame: Baseline (end of Phase 2), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]

3.  Secondary:   Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3   [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3 ]

4.  Secondary:   Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3   [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3 ]

5.  Secondary:   Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2   [ Time Frame: Baseline (end of ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 (Ph2) Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, + Confirmation of Partial Nonresponse Phase) ]

6.  Secondary:   Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3   [ Time Frame: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

7.  Secondary:   Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 (Ph2) Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

8.  Secondary:   Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3   [ Time Frame: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

9.  Secondary:   Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2   [ Time Frame: Baseline (end of Ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

10.  Secondary:   Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3   [ Time Frame: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

11.  Secondary:   Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2   [ Time Frame: Baseline (end of Ph 1), Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

12.  Secondary:   Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3   [ Time Frame: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

13.  Secondary:   Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2   [ Time Frame: Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

14.  Secondary:   Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2   [ Time Frame: Baseline (end of Ph 1), Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

15.  Secondary:   Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3   [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

16.  Secondary:   Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2   [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

17.  Secondary:   Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3   [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

18.  Secondary:   Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2   [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

19.  Secondary:   Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3   [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

20.  Secondary:   Number of Participants Maintaining Remission During Phase 3   [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

21.  Secondary:   Proportion of Participants Discontinuing For Any Reason Through Week 52 (During Phase 3)   [ Time Frame: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

22.  Secondary:   Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2   [ Time Frame: During Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

23.  Secondary:   Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2   [ Time Frame: During Phase 2. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

24.  Secondary:   Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2   [ Time Frame: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

25.  Secondary:   Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2   [ Time Frame: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

26.  Secondary:   Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2   [ Time Frame: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

27.  Secondary:   Median Baseline and Change From Baseline in ECG Measurements During Phase 2   [ Time Frame: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

28.  Secondary:   Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2   [ Time Frame: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

29.  Secondary:   Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2   [ Time Frame: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

30.  Secondary:   Median Baseline and Change From Baseline in Weight Vital Sign Measurements At Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

31.  Secondary:   Median Baseline and Change From Baseline in Body Mass Index (BMI) Vital Sign Measurements at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

32.  Secondary:   Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample   [ Time Frame: Baseline ]

33.  Secondary:   Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

34.  Secondary:   Median Baseline and Change From Baseline in Heart Rate Measurements During Phase 2   [ Time Frame: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

35.  Secondary:   Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid   [ Time Frame: Baseline ]

36.  Secondary:   Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

37.  Secondary:   Median Baseline Eosinophils (Relative) and Neutrophils (Relative)   [ Time Frame: Baseline ]

38.  Secondary:   Median Change From Baseline in Eosinophils (Relative) and Neutrophils (Relative)   [ Time Frame: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

39.  Secondary:   Median Baseline Hemoglobin   [ Time Frame: Baseline ]

40.  Secondary:   Median Change From Baseline in Hemoglobin   [ Time Frame: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

41.  Secondary:   Median Baseline Hematocrit   [ Time Frame: Baseline ]

42.  Secondary:   Median Change From Baseline in Hematocrit   [ Time Frame: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

43.  Secondary:   Median Baseline Homeostasis Model Assessment 2 (HOMA2)-Percent Beta   [ Time Frame: Baseline ]

44.  Secondary:   Median Baseline Homeostasis Model Assessment 2 HOMA2-Insulin Resistance (IR)   [ Time Frame: Baseline ]

45.  Secondary:   Median Change From Baseline in Homeostasis Model Assessment 2(HOMA2)-Percent Beta at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint (endpoint of a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

46.  Secondary:   Median Change From Baseline in HOMA2 Model Assesses Insulin Resistance (HOMA2-IR) at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint (endpoint of a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase) ]

47.  Secondary:   Median Baseline Platelet Count   [ Time Frame: Baseline ]

48.  Secondary:   Median Change From Baseline in Platelet Count at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

49.  Secondary:   Median Baseline Prolactin   [ Time Frame: Baseline ]

50.  Secondary:   Median Change From Baseline in Prolactin at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

51.  Secondary:   Median Baseline Leukocytes   [ Time Frame: Baseline ]

52.  Secondary:   Median Change From Baseline in Leukocytes at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

53.  Secondary:   Baseline Abnormal Involuntary Movement Scale (AIMS)   [ Time Frame: Baseline ]

54.  Secondary:   Unadjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

55.  Secondary:   Baseline in Simpson-Angus Scale (SAS) Total Score   [ Time Frame: Baseline ]

56.  Secondary:   Unadjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

57.  Secondary:   Baseline in Barnes Akathisia Global Clinical Assessment   [ Time Frame: Baseline ]

58.  Secondary:   Unadjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Phase 2 Endpoint   [ Time Frame: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase) ]

59.  Secondary:   Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3   [ Time Frame: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

60.  Secondary:   Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity   [ Time Frame: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

61.  Secondary:   Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3   [ Time Frame: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

62.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Systolic BP During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

63.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Diastolic BP During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

64.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Heart Rate During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

65.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Systolic BP During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

66.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Diastolic BP During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

67.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Heart Rate During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

68.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Systolic BP During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

69.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Diastolic BP During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

70.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Heart Rate During Phase 3   [ Time Frame: Baseline, During Phase 3 (for highest/lowest values), Week 52 ]

71.  Secondary:   Baseline and Adjusted Mean Change From Baseline in Weight   [ Time Frame: Baseline, Weeks 12, 24, 36, 52, During Phase 3 (for highest value) ]

72.  Secondary:   Number of Participants Showing Relevant Weight Gain During Phase 3   [ Time Frame: Weeks 12, 24, 36, 52, 52 (LOCF), and throughout Phase 3 (for 'at any time' assessment) ]

73.  Secondary:   Number of Participants Showing Relevant Weight Loss During Phase 3   [ Time Frame: Weeks 12, 24, 36, 52, 52 (LOCF), and throughout Phase 3 (for 'at any time' assessment) ]

74.  Secondary:   Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3   [ Time Frame: Baseline, Week 12, Week 24, Week 36, Week 52, Week 52 (LOCF), During Phase 3 (for lowest/highest values) ]

75.  Secondary:   Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3   [ Time Frame: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

76.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Alkaline Phosphatase (ALP), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

77.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in ALT, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

78.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in AST, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

79.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in BUN, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

80.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Total Cholesterol (Fasting), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

81.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Creatine Kinase, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

82.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Creatinine, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

83.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Eosinophils (Relative), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

84.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Glucose (Fasting), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

85.  Secondary:   Median Baseline, Change From Baseline, and Lowest Value of Change in Hemoglobin, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value) ]

86.  Secondary:   Median Baseline, Change From Baseline, and Lowest Value of Change in Hematocrit, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value) ]

87.  Secondary:   Median Baseline, Change From Baseline, and Lowest Value of Change in HDL Cholesterol (Fasting), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value ]

88.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-Percent Beta, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value ]

89.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-IR, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value ]

90.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Lactate Dehydrogenase, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

91.  Secondary:   Median Baseline, Change From Baseline, and Highest Change Value in LDL Cholesterol (Fasting), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

92.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Neutrophils (Relative), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

93.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Platelet Count, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest/lowest value) ]

94.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Prolactin, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

95.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Total Bilirubin, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

96.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Triglycerides (Fasting), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

97.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Uric Acid, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

98.  Secondary:   Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Leukocytes, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest/lowest value) ]

99.  Secondary:   Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3   [ Time Frame: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

100.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in QT Interval Corrected for Heart Rate (QTc) Bazett, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

101.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in QTc (0.33), Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

102.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in PR, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

103.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in RR, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

104.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in QRS, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

105.  Secondary:   Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3   [ Time Frame: Baseline, Weeks 4,8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change) ]

106.  Secondary:   Median Baseline, Change From Baseline, and Highest Value of Change in Heart Rate, Phase 3 Safety Sample   [ Time Frame: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value) ]

107.  Secondary:   Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3   [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change) ]

108.  Secondary:   Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3   [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change) ]

109.  Secondary:   Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3   [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change) ]

110.  Secondary:   Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3   [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change) ]

111.  Secondary:   Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3   [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change) ]

112.  Secondary:   Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3   [ Time Frame: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

113.  Secondary:   Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)   [ Time Frame: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72 of LTE Phase. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

114.  Secondary:   Extension Phase: Mean Change From Baseline in CGI-BP (Mania) Severity of Illness at Extension Phase Endpoint   [ Time Frame: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

115.  Secondary:   Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Depression) at Extension Phase Endpoint   [ Time Frame: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

116.  Secondary:   Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase   [ Time Frame: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

117.  Secondary:   Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase   [ Time Frame: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

118.  Secondary:   Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Overall) at Extension Phase Endpoint   [ Time Frame: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

119.  Secondary:   Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations   [ Time Frame: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

120.  Secondary:   Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase   [ Time Frame: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

121.  Secondary:   Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities   [ Time Frame: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

122.  Secondary:   Extension Phase: Adverse Events (AEs), by Maximum Intensity   [ Time Frame: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

123.  Secondary:   Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities   [ Time Frame: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]

124.  Secondary:   Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities   [ Time Frame: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks]) ]


  Serious Adverse Events


  Other Adverse Events


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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided by Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications automatically indexed to this study:

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00261443     History of Changes
Other Study ID Numbers: CN138-189
Study First Received: December 1, 2005
Results First Received: January 28, 2011
Last Updated: November 7, 2013
Health Authority: United States: Food and Drug Administration