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

Official Title: “Efficacy of Aripiprazole in Combination With Lithium or Valproate in the Long-Term Maintenance Treatment of Bipolar I Disorder in Outpatients Partially Nonresponsive to Lithium or Valproate Monotherapy”

The purpose of this clinical research study is to learn if outpatients with bipolar mania who are partially nonresponsive to lithium or valproate monotherapy can achieve stable symptoms on a combination treatment of aripiprazole plus lithium or valproate.

Intervention(s) in this Clinical Trial

• Drug: Lithium or Valproate with placebo (PBO)
  • Tablets, Oral, once daily lithium 250-2100 mg/day valproate 250-2500mg/day Placebo once daily
• Drug: Lithium or Valproate with Aripiprazole
  • Tablets, Oral, once daily, 52 weeks post randomization (Pre-Randomization Phases 13-24 weeks) lithium 250-2100 mg/day valproate 250-2500mg/day aripiprazole 15-30 mg/day

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: A1
  • /Active Comparator
• Experimental: A2

Primary Measures

• 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])
    Safety Issue?: No

Secondary Measures

• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• Median Baseline Eosinophils (Relative) and Neutrophils (Relative)
  • Time Frame: Baseline
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• Median Baseline Hemoglobin
  • Time Frame: Baseline
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• Median Baseline Hematocrit
  • Time Frame: Baseline
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• Median Baseline Homeostasis Model Assessment 2 (HOMA2)-Percent Beta
  • Time Frame: Baseline
    Safety Issue?: Yes
• Median Baseline Homeostasis Model Assessment 2 HOMA2-Insulin Resistance (IR)
  • Time Frame: Baseline
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• Median Baseline Platelet Count
  • Time Frame: Baseline
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• Median Baseline Prolactin
  • Time Frame: Baseline
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• Median Baseline Leukocytes
  • Time Frame: Baseline
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• Baseline Abnormal Involuntary Movement Scale (AIMS)
  • Time Frame: Baseline
    Safety Issue?: No
• 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)
    Safety Issue?: No
• Baseline in Simpson-Angus Scale (SAS) Total Score
  • Time Frame: Baseline
    Safety Issue?: No
• 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)
    Safety Issue?: No
• Baseline in Barnes Akathisia Global Clinical Assessment
  • Time Frame: Baseline
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: Yes
• 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])
    Safety Issue?: Yes
• 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])
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• Baseline and Adjusted Mean Change From Baseline in Weight
  • Time Frame: Baseline, Weeks 12, 24, 36, 52, During Phase 3 (for highest value)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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])
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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])
    Safety Issue?: No
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: Yes
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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])
    Safety Issue?: Yes
• 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])
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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])
    Safety Issue?: No
• 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])
    Safety Issue?: Yes
• 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])
    Safety Issue?: Yes
• 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])
    Safety Issue?: Yes
• 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])
    Safety Issue?: Yes
• 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])
    Safety Issue?: Yes
• 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])
    Safety Issue?: Yes

Inclusion Criteria:

• Men and women > or = to 18 years of age meeting Diagnostic and Statistical Manual for
• Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder, currently experiencing a manic or mixed episode with a history of one or more manic or mixed episodes or sufficient severity to require hospitalization and/or treatment with a mood stabilizer or antipsychotic.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Bristol-Myers Squibb Industry

Overall Clinical Trial Officials and Contacts

Bristol-Myers Squibb Study Director Bristol-Myers Squibb  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00261443

Study ID Number: CN138-189

ClinicalTrials.gov Identifier: NCT00261443

Health Authority: United States: Food and Drug Administration

BMS Clinical Trials Disclosure

For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm