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

Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00261443
Collaborator
Otsuka America Pharmaceutical (Industry)
1,270
Enrollment
83
Locations
2
Arms
49
Duration (Months)
15.3
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Lithium or Valproate with placebo (PBO)
  • Drug: Lithium or Valproate with Aripiprazole
 Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
1270 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Study Start Date :
Sep 1, 2005
Actual Primary Completion Date :
Jun 1, 2009
Actual Study Completion Date :
Oct 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: A1

/Active Comparator

Drug: Lithium or Valproate with placebo (PBO)
Tablets, Oral, once daily lithium 250-2100 mg/day valproate 250-2500mg/day Placebo once daily
Experimental: A2

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
Other Names:
  • Abilify
  • BMS-337039

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3 [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])]

      Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: hospitalization for a manic, mixed or depressive episode; serious adverse event of worsening disease under study accompanied by a Y-MRS > 16 and/or a MADRS > 16; discontinuation due to lack of efficacy as determined by the investigator accompanied by a Y-MRS > 16 and/or a MADRS > 16.

    Secondary Outcome Measures

    1. 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 [Baseline (end of Phase 2), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.

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

      Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: relapse is defined as any of the following events accompanied by a Young-Mania Rating Scale (Y-MRS) >16 and/or a Montgomery Åsberg Depression Rating Scale (MADRS) >16; serious adverse event of worsening disease, or discontinuation by the investigator for lack of efficacy. A hospitalization for a manic, mixed, or depressive episode does meet the criteria for relapse, however does not require an accompanying Y-MRS and/or MADRS score >16.

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

      Kaplan Meier estimated survival rate. Relapse is defined as any of the following events accompanied by a YMRS > 16 and/or a MADRS > 16; serious adverse event of worsening disease, or discontinuation by the investigator for lack of efficacy. A hospitalization for a manic, mixed, or depressive episode does meet the criteria for relapse, however does not require an accompanying Y-MRS and/or MADRS score > 16.

    4. Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2 [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)]

      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 (best) to 60 (worst).

    5. Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3 [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])]

      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. 7 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 (best) to 60 (worst).

    6. 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 [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)]

      The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.

    7. Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3 [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])]

      The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.

    8. Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2 [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)]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.

    9. Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3 [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])]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.

    10. Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2 [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)]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from baseline (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.

    11. Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3 [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])]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.

    12. Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2 [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)]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall change from preceding phase items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).

    13. Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2 [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)]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from baseline (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.

    14. Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3 [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])]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.

    15. Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2 [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)]

      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).

    16. Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3 [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])]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).

    17. Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2 [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)]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).

    18. Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3 [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])]

      Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).

    19. Number of Participants Maintaining Remission During Phase 3 [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])]

      Remission is defined as Y-MRS Total Score <=12 and MADRS Total Score <=12.

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

    21. Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2 [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)]

      Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

    22. Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2 [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)]

      AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).

    23. Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2 [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)]

      Sinus Tachycardia: ≥120bpm+↑≥15bpm+no current diagnosis of supraventricular (SV) or ventricular tachycardia or atrial fibrillation (AF) or flutter or other rhythm abnormality (RA). Sinus Bradycardia:≥50bpm+↓≥15bpm+no current diagnosis of AF or flutter or other RA. AF:not present→present or present at rate <100bpm pretreatment to present with rate ≥100bpm+increase of ≥15bpm. AV=atrioventricular; PR=PR interval. Other Intraventricular Block: QRS wave ≥0.12 sec+↑≥0.02 sec+no current diagnosis of left or right bundle branch block. Old Infarction not present→present at ≥12 weeks post study entry.

    24. Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2 [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)]

      Heart Rate: increase, ≥120 beats per minute (bpm) and ≥15 relative to baseline (RBL); decrease, ≤50 bpm and ≥15 RBL. Systolic BP: increase, ≥180 mmHg and ≥20 RBL; decrease, ≤90 mmHg and ≥20 RBL. Diastolic BP: increase, ≥105 mmHg and ≥15 RBL; decrease, ≤50 mmHg and ≥15 RBL. For patients missing a baseline value, an on-treatment value was considered potentially clinically relevant if the value meets the criterion value.

    25. Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2 [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)]

      ULN=upper limit of normal; HDL=high density lipoprotein; LDL=low density lipoprotein. Values for ULN are provided by the lab in the database and could be different for each individual patient based on characteristics such as age, gender, or other patient attributes.

    26. Median Baseline and Change From Baseline in ECG Measurements During Phase 2 [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)]

    27. Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2 [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. Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2 [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. Median Baseline and Change From Baseline in Weight Vital Sign Measurements At Phase 2 Endpoint [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)]

    30. Median Baseline and Change From Baseline in Body Mass Index (BMI) Vital Sign Measurements at Phase 2 Endpoint [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)]

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

    32. 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 [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)]

    33. Median Baseline and Change From Baseline in Heart Rate Measurements During Phase 2 [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)]

    34. 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 [Baseline]

    35. 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 [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)]

    36. Median Baseline Eosinophils (Relative) and Neutrophils (Relative) [Baseline]

    37. Median Change From Baseline in Eosinophils (Relative) and Neutrophils (Relative) [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)]

    38. Median Baseline Hemoglobin [Baseline]

    39. Median Change From Baseline in Hemoglobin [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)]

    40. Median Baseline Hematocrit [Baseline]

    41. Median Change From Baseline in Hematocrit [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)]

    42. Median Baseline Homeostasis Model Assessment 2 (HOMA2)-Percent Beta [Baseline]

      HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'

    43. Median Baseline Homeostasis Model Assessment 2 HOMA2-Insulin Resistance (IR) [Baseline]

      HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'

    44. Median Change From Baseline in Homeostasis Model Assessment 2(HOMA2)-Percent Beta at Phase 2 Endpoint [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)]

      HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'

    45. Median Change From Baseline in HOMA2 Model Assesses Insulin Resistance (HOMA2-IR) at Phase 2 Endpoint [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)]

      HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'

    46. Median Baseline Platelet Count [Baseline]

    47. Median Change From Baseline in Platelet Count at Phase 2 Endpoint [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)]

    48. Median Baseline Prolactin [Baseline]

    49. Median Change From Baseline in Prolactin at Phase 2 Endpoint [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)]

    50. Median Baseline Leukocytes [Baseline]

    51. Median Change From Baseline in Leukocytes at Phase 2 Endpoint [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)]

    52. Baseline Abnormal Involuntary Movement Scale (AIMS) [Baseline]

      The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.

    53. Unadjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) at Phase 2 Endpoint [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)]

      The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.

    54. Baseline in Simpson-Angus Scale (SAS) Total Score [Baseline]

      The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50.(lower score=less severe). Negative change scores indicate improvement.

    55. Unadjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score at Phase 2 Endpoint [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)]

      The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50(lower score=less severe). Negative change scores indicate improvement.

    56. Baseline in Barnes Akathisia Global Clinical Assessment [Baseline]

      The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.

    57. Unadjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Phase 2 Endpoint [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)]

      The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.

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

      Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

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

      AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).

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

      Heart Rate: increase, ≥120 beats per minute (bpm) and ≥15 relative to baseline (RBL); decrease, ≤50 bpm and ≥15 RBL. Systolic BP: increase, ≥180 mmHg and ≥20 RBL; decrease, ≤90 mmHg and ≥20 RBL. Diastolic BP: increase, ≥105 mmHg and ≥15 RBL; decrease, ≤50 mmHg and ≥15 RBL. For patients missing a baseline value, an on-treatment value was considered potentially clinically relevant if the value meets the criterion value.

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

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

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

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

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

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

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

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

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

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

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

      Relevant weight gain: >=7% increase from baseline

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

      Relevant weight loss: >=7% decrease from baseline

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

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

      ULN=upper limit of normal; Hb=hemoglobin

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

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

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

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

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

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

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

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

      The change values reported are the median of (post baseline percentage (of white blood cell count) minus baseline percentage (of white blood cell count).

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

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

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

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

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

      HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'

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

      HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'

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

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

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

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

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

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

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

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

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

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

      Sinus Tachycardia: ≥120bpm+↑≥15bpm+no current diagnosis of supraventricular (SV) or ventricular tachycardia or atrial fibrillation (AF) or flutter or other rhythm abnormality (RA). Sinus Bradycardia:≥50bpm+↓≥15bpm+no current diagnosis of AF or flutter or other RA. AF:not present→present or present at rate <100bpm pretreatment to present with rate ≥100bpm+increase of ≥15bpm. AV=atrioventricular; PR=PR interval. Other Intraventricular Block: QRS wave ≥0.12 sec+↑≥0.02 sec+no current diagnosis of left or right bundle branch block. Old Infarction not present→present at ≥12 weeks post study entry.

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

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

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

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

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

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

      The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50(lower scores=less severe). Negative change scores indicate improvement.

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

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

      The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.

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

      The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 8 Score range from 0 to 4. A negative score signifies improvement.

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

      The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 9 Score range from 0 to 4. A negative score signifies improvement.

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

      The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 10 Score range from 0 to 4. A negative score signifies improvement.

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

      The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.

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

    112. Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania) [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])]

      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 normal and 7 being very severely ill). A negative change score signifies improvement.

    113. Extension Phase: Mean Change From Baseline in CGI-BP (Mania) Severity of Illness at Extension Phase Endpoint [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])]

      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 normal and 7 being very severely ill). A negative change score signifies improvement.

    114. Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Depression) at Extension Phase Endpoint [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])]

      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 normal and 7 being very severely ill). A negative change score signifies improvement.

    115. Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase [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])]

      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 normal and 7 being very severely ill). A negative change score signifies improvement.

    116. Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase [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])]

      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 normal and 7 being very severely ill). A negative change score signifies improvement.

    117. Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Overall) at Extension Phase Endpoint [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])]

      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 normal and 7 being very severely ill). A negative change score signifies improvement.

    118. Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations [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])]

      Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

    119. Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase [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])]

      Metabolic abnormalities considered by the investigator as clinically relevant. (Need normal values for each.)

    120. Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities [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])]

      Vital sign abnormalities considered by the investigator as clinically relevant.

    121. Extension Phase: Adverse Events (AEs), by Maximum Intensity [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])]

      AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).

    122. Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities [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])]

      Chemistry, hematology, and urinalysis abnormalities considered by the investigator as clinically relevant. Hematocrit: ≤37%(M)/≤32%(F)+3 percentage pts↓from baseline.

    123. Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities [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])]

      ECG abnormalities considered by the investigator as clinically relevant.Left Bundle Branch Block: Not present at Baseline--> present post-baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tuscaloosa Va Medical Center Tuscaloosa Alabama United States 35404
    2 Pravin Kansagra, M.D. Anaheim California United States 92801
    3 Psychopharmacology Research Network Of Torrance Cerritos California United States 90703
    4 Atp Clinical Research, Inc. Costa Mesa California United States 92626
    5 Us Clinical Research Centers, Llc Costa Mesa California United States 92627
    6 Va Long Beach Healthcare System Long Beach California United States 90822
    7 Synergy Clinical Research Center National City California United States 91950
    8 University Of California, Irvine Medical Center Orange California United States 92868
    9 Clinical Neuroscience Solutions, Inc. Orlando Florida United States 32806
    10 University Of South Florida Tampa Florida United States 33613
    11 Carman Research Smyrna Georgia United States 30080
    12 University Of Massachusetts Medical School Worcester Massachusetts United States 01605
    13 Psych Care Consultants Research St. Louis Missouri United States 63128
    14 Cns Research Institute, P.C. Clementon New Jersey United States 08021
    15 Neuropsychiatric Research Associates New York New York United States 10128
    16 Behavioral Medical Research Of Staten Island Staten Island New York United States 10305
    17 Richmond Behavioral Associates Staten Island New York United States 10312
    18 Psychiatry And Clinical Research Raleigh North Carolina United States 27609
    19 Rakesh Ranjan, Md & Associates, Inc. Beachwood Ohio United States 44122
    20 University Of Cincinnati Medical Center Cincinnati Ohio United States 45267
    21 Metro Health Medical Center Cleveland Ohio United States 44109
    22 Midwest Clinical Research Center Dayton Ohio United States 45408
    23 Portland Va Medical Center Portland Oregon United States 97201
    24 Senior Adults Specialty Research, Inc. Austin Texas United States 78757
    25 Futuresearch Trials Dallas Texas United States 75231
    26 Insite Clinical Research Desoto Texas United States 75115
    27 Red Oak Psychiatry Associates, Pa Houston Texas United States 77090
    28 University Of Utah School Of Medicine Salt Lake City Utah United States 84132
    29 Northwest Clinical Research Center Bellevue Washington United States 98004
    30 Local Institution Salvador Bahia Brazil 40325
    31 Local Institution Aparecida De Goinia Goias Brazil 74922
    32 Local Institution Pelotas Rio Grande Do Sul Brazil 96030 003
    33 Local Institution Rio De Janeiro Brazil 21020
    34 Local Institution Sao Paulo Brazil 02340
    35 Local Institution Sao Paulo Brazil 05403
    36 Local Institution Bourgas Bulgaria 8000
    37 Local Institution Rousse Bulgaria 7002
    38 Local Institution Rijeka Croatia 51-000
    39 Local Institution Split Croatia 21000
    40 Local Institution Zadar Croatia 23000
    41 Local Institution Zagreb Croatia 10 090
    42 Local Institution Brno Czech Republic 610 00
    43 Local Institution Brno Czech Republic 625 00
    44 Local Institution Havirov Czech Republic 736 01
    45 Local Institution Litomerice Czech Republic 412 01
    46 Local Institution Prague 2 Czech Republic 120 00
    47 Local Institution Praha 6 Czech Republic 160 00
    48 Local Institution Prerov Czech Republic 75002
    49 Local Institution Nantes Cedex 01 France 44035
    50 Local Institution Dole France 39100
    51 Local Institution Henin Beaumont France 62251
    52 Local Institution Jonzac Cedex France 175003
    53 Local Institution La Seyne Sur Mer France 83500
    54 Local Institution Marseille France 13009
    55 Local Institution Nantes France 44000
    56 Local Institution Nimes France 30900
    57 Local Institution Rennes France 35000
    58 Local Institution Hyderabad Andhra Pradesh India 500 034
    59 Local Institution Ahmedabad Gujarat India 380 006
    60 Local Institution Ahmedabad Gujarat India 6577647
    61 Local Institution Kalyan (West) Maharashtra India 421 301
    62 Local Institution Nagur Maharashtra India 440010
    63 Local Institution Pune Maharashtra India 400 001
    64 Local Institution Mangalore Manipal India 576 104
    65 Local Institution Mumbai Sion (W) India 400 022
    66 Local Institution Delhi India 110 092
    67 Local Institution Hyderabad India 500 038
    68 Local Institution Mumbai India 400 008
    69 Local Institution Mumbai India 400 058
    70 Local Institution New Delhi India 110 002
    71 Local Institution New Delhi India 110 065
    72 Local Institution Izhevsk Russian Federation 426053
    73 Local Institution Moscow Russian Federation 107258
    74 Local Institution Nizhny Novgorod Russian Federation 603107
    75 Local Institution Saint-Petersburg Russian Federation 191119
    76 Local Institution Saratov Russian Federation 410028
    77 Local Institution St-Petersburg Russian Federation 190000
    78 Local Institution Tomsk Russian Federation 634014
    79 Local Institution Pretoria Gauteng South Africa 0001
    80 Local Institution Berea Kwa Zulu Natal South Africa 4001
    81 Local Institution Durban Kwa Zulu Natal South Africa 4001
    82 Local Institution Cape Town Western Cape South Africa 7708
    83 Local Institution Paarl Western Cape South Africa 7646

    Sponsors and Collaborators

    • Otsuka Pharmaceutical Development & Commercialization, Inc.
    • Otsuka America Pharmaceutical

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00261443
    Other Study ID Numbers:
    • CN138-189
    First Posted:
    Dec 5, 2005
    Last Update Posted:
    Dec 2, 2013
    Last Verified:
    Apr 1, 2011
    Keywords provided by , ,
    Bipolar I Disorder with a recent manic or mixed episode
    Additional relevant MeSH terms:
    Bipolar Disorder
    Valproic Acid
    Aripiprazole
    Lithium Carbonate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Pre-Randomized Participants Placebo Aripiprazole
    Arm/Group Description 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. 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. 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.
    Period Title: 1: Confirmation of Partial Nonresponse
    STARTED 1270 0 0
    COMPLETED 686 0 0
    NOT COMPLETED 584 0 0
    Period Title: 1: Confirmation of Partial Nonresponse
    STARTED 686 0 0
    COMPLETED 346 0 0
    NOT COMPLETED 340 0 0
    Period Title: 1: Confirmation of Partial Nonresponse
    STARTED 0 169 168
    COMPLETED 0 89 103
    NOT COMPLETED 0 80 65
    Period Title: 1: Confirmation of Partial Nonresponse
    STARTED 0 19 23
    COMPLETED 0 16 21
    NOT COMPLETED 0 3 2

    Baseline Characteristics

    Arm/Group Title Placebo Aripiprazole Total
    Arm/Group Description 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 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 of all reporting groups
    Overall Participants 169 168 337
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    38.8
    (12.29)
    39.2
    (12.43)
    39.0
    (12.34)
    Sex: Female, Male (Count of Participants)
    Female
    98
    58%
    87
    51.8%
    185
    54.9%
    Male
    71
    42%
    81
    48.2%
    152
    45.1%
    Race/Ethnicity, Customized (participants) [Number]
    White
    112
    66.3%
    118
    70.2%
    230
    68.2%
    Black/African American
    19
    11.2%
    12
    7.1%
    31
    9.2%
    Asian
    33
    19.5%
    34
    20.2%
    67
    19.9%
    Other
    5
    3%
    4
    2.4%
    9
    2.7%
    Race/Ethnicity, Customized (Number) [Number]
    Hispanic/Latino
    3
    1.8%
    5
    3%
    8
    2.4%
    Not Hispanic or Latino
    55
    32.5%
    56
    33.3%
    111
    32.9%
    Non-US
    111
    65.7%
    107
    63.7%
    218
    64.7%
    Region of Enrollment (participants) [Number]
    France
    8
    4.7%
    9
    5.4%
    17
    5%
    United States
    58
    34.3%
    61
    36.3%
    119
    35.3%
    Czech Republic
    18
    10.7%
    14
    8.3%
    32
    9.5%
    Brazil
    28
    16.6%
    27
    16.1%
    55
    16.3%
    Croatia
    3
    1.8%
    4
    2.4%
    7
    2.1%
    Russian Federation
    17
    10.1%
    15
    8.9%
    32
    9.5%
    South Africa
    4
    2.4%
    4
    2.4%
    8
    2.4%
    India
    33
    19.5%
    34
    20.2%
    67
    19.9%
    Body Mass Index (BMI) Category (Number) [Number]
    <18.5 kg/m^2
    5
    3%
    0
    0%
    5
    1.5%
    18.5 kg/m^2 to <25 kg/m^2
    58
    34.3%
    49
    29.2%
    107
    31.8%
    25 kg/m^2 to <30 kg/m^2
    50
    29.6%
    63
    37.5%
    113
    33.5%
    >= 30 kg/m^2
    56
    33.1%
    56
    33.3%
    112
    33.2%
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    28.7
    (7.72)
    28.5
    (6.00)
    28.6
    (6.90)
    CGI-BP Change from Preceding Phase Score (Depression) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    3.0
    (1.34)
    3.0
    (1.31)
    3.0
    (1.32)
    CGI-BP Change from Preceding Phase Score (Mania) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.6
    (0.81)
    1.4
    (0.63)
    1.5
    (0.72)
    CGI-BP Change from Preceding Phase Score (Overall) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.6
    (0.85)
    1.5
    (0.69)
    1.6
    (0.77)
    CGI-BP Severity of Illness Score (Depression) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.3
    (0.57)
    1.4
    (0.70)
    1.4
    (0.64)
    CGI-BP Severity of Illness Score (Mania) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.5
    (0.72)
    1.5
    (0.72)
    1.5
    (0.72)
    CGI-BP Severity of Illness Score (Overall) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.6
    (0.76)
    1.7
    (0.83)
    1.6
    (0.79)
    Montgomery Åsberg Depression Rating Scale (MADRS) Total Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    3.7
    (3.45)
    4.1
    (3.82)
    3.9
    (3.64)
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    81.3
    (25.11)
    80.6
    (18.89)
    81.0
    (22.20)
    Young-Mania Rating Scale (Y-MRS) Total Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    4.1
    (3.31)
    4.1
    (3.56)
    4.1
    (3.43)

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
    Description Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: hospitalization for a manic, mixed or depressive episode; serious adverse event of worsening disease under study accompanied by a Y-MRS > 16 and/or a MADRS > 16; discontinuation due to lack of efficacy as determined by the investigator accompanied by a Y-MRS > 16 and/or a MADRS > 16.
    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])

    Outcome Measure Data

    Analysis Population Description
    Randomized Sample; n=number of participants at risk at each time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 169 168
    Proportion at Week 0 (n=169, 168)
    1.00
    0.6%
    1.00
    0.6%
    Proportion at Week 4 (n=153, 148)
    0.95
    0.6%
    0.96
    0.6%
    Proportion at Week 8 (n=148, 139)
    0.93
    0.6%
    0.94
    0.6%
    Proportion at Week 12 (n=142, 133)
    0.90
    0.5%
    0.93
    0.6%
    Proportion at Week 16 (n=131, 130)
    0.87
    0.5%
    0.92
    0.5%
    Proportion at Week 20 (n=122, 128)
    0.83
    0.5%
    0.91
    0.5%
    Proportion at Week 24 (n=113, 125)
    0.81
    0.5%
    0.89
    0.5%
    Proportion at Week 28 (n=105, 121)
    0.77
    0.5%
    0.89
    0.5%
    Proportion at Week 32 (n=102, 114)
    0.76
    0.4%
    0.84
    0.5%
    Proportion at Week 36 (n=99, 111)
    0.75
    0.4%
    0.84
    0.5%
    Proportion at Week 40 (n=95, 110)
    0.73
    0.4%
    0.84
    0.5%
    Proportion at Week 44 (n=91,107)
    0.73
    0.4%
    0.84
    0.5%
    Proportion at Week 48 (n=88, 98)
    0.71
    0.4%
    0.83
    0.5%
    Proportion at Week 52 (n=5, 8)
    0.71
    0.4%
    0.83
    0.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments Stratified Log-rank Test, controlling for type of mood stabilizer and type of mood episode
    Method Stratified Log-rank Test
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.544
    Confidence Interval (2-Sided) 95%
    0.332 to 0.893
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox proportional hazards model, with type of mood stabilizer and type of index mood episode as stratification factors, and treatment group as covariate.
    2. Secondary Outcome
    Title 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
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
    Time Frame Baseline (end of Phase 2), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

    Outcome Measure Data

    Analysis Population Description
    LOCF data set, phase 3 efficacy sample; n=number of participants evaluated at given time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Mean Baseline (n=164, 162)
    1.54
    (0.059)
    1.54
    (0.058)
    Mean Change from Baseline to Week 4 (n=160, 162)
    0.01
    (0.052)
    0.05
    (0.050)
    Mean Change from Baseline to Week 8 (n=164, 162)
    0.05
    (0.054)
    0.01
    (0.053)
    Mean Change from Baseline to Week 12 (n=164, 162)
    0.12
    (0.063)
    0.07
    (0.062)
    Mean Change from Baseline to Week 16 (n=164, 162)
    0.19
    (0.064)
    0.07
    (0.063)
    Mean Change from Baseline to Week 20 (n=164, 162)
    0.23
    (0.071)
    0.07
    (0.070)
    Mean Change from Baseline to Week 24 (n=164, 162)
    0.25
    (0.074)
    0.05
    (0.073)
    Mean Change from Baseline to Week 28 (n=164, 162)
    0.31
    (0.082)
    0.10
    (0.080)
    Mean Change from Baseline to Week 32 (n=164, 162)
    0.27
    (0.078)
    0.08
    (0.076)
    Mean Change from Baseline to Week 36 (n=164, 162)
    0.30
    (0.079)
    0.05
    (0.078)
    Mean Change from Baseline to Week 40 (n=164, 162)
    0.27
    (0.080)
    0.05
    (0.079)
    Mean Change from Baseline to Week 44 (n=164, 162)
    0.33
    (0.082)
    0.06
    (0.080)
    Mean Change from Baseline to Week 48 (n=164, 162)
    0.33
    (0.082)
    0.05
    (0.081)
    Mean Change from Baseline to Week 52 (n=164, 162)
    0.32
    (0.083)
    0.04
    (0.082)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Baseline Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.911
    Comments ANOVA model, controlling for treatment, mood stabilizer, and index mood episode used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, difference in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.01
    Confidence Interval (2-Sided) 95%
    -0.16 to 0.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 4 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.557
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.09 to 0.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 8 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.596
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.04
    Confidence Interval (2-Sided) 95%
    -0.18 to 0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 12 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.522
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.05
    Confidence Interval (2-Sided) 95%
    -0.22 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 16 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.142
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.30 to 0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 20 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.092
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.16
    Confidence Interval (2-Sided) 95%
    -0.35 to 0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 24 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.039
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.20
    Confidence Interval (2-Sided) 95%
    -0.40 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 28 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.050
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.21
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 32 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.064
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -0.40 to 0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 36 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.25
    Confidence Interval (2-Sided) 95%
    -0.46 to -0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 40 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.039
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.22
    Confidence Interval (2-Sided) 95%
    -0.43 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 44 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.27
    Confidence Interval (2-Sided) 95%
    -0.48 to -0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 48 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.50 to -0.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 52 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.28
    Confidence Interval (2-Sided) 95%
    -0.50 to -0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
    Description Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: relapse is defined as any of the following events accompanied by a Young-Mania Rating Scale (Y-MRS) >16 and/or a Montgomery Åsberg Depression Rating Scale (MADRS) >16; serious adverse event of worsening disease, or discontinuation by the investigator for lack of efficacy. A hospitalization for a manic, mixed, or depressive episode does meet the criteria for relapse, however does not require an accompanying Y-MRS and/or MADRS score >16.
    Time Frame Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3

    Outcome Measure Data

    Analysis Population Description
    Randomized sample, n=number of participants at risk at given time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 169 168
    Proportion at Week 0 (n=169,168)
    1.00
    0.6%
    1.00
    0.6%
    Proportion at Week 4 (n=153,148)
    0.99
    0.6%
    0.99
    0.6%
    Proportion at Week 8 (n=148,139)
    0.99
    0.6%
    0.98
    0.6%
    Proportion at Week 12 (n=142,133)
    0.97
    0.6%
    0.97
    0.6%
    Proportion at Week 16 (n=132,130)
    0.95
    0.6%
    0.97
    0.6%
    Proportion at Week 20 (n=122,128)
    0.93
    0.6%
    0.97
    0.6%
    Proportion at Week 24 (n=113,125)
    0.91
    0.5%
    0.97
    0.6%
    Proportion at Week 28 (n=105,121)
    0.90
    0.5%
    0.97
    0.6%
    Proportion at Week 32 (n=102,115)
    0.89
    0.5%
    0.95
    0.6%
    Proportion at Week 36 (n=99, 111)
    0.88
    0.5%
    0.95
    0.6%
    Proportion at Week 40 (n=95,110)
    0.87
    0.5%
    0.95
    0.6%
    Proportion at Week 44 (n=91,107)
    0.86
    0.5%
    0.95
    0.6%
    Proportion at Week 48 (n=88, 98)
    0.85
    0.5%
    0.95
    0.6%
    Proportion at Week 52 (n=5, 8)
    0.85
    0.5%
    0.95
    0.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments Stratified Log-rank Test, controlling for type of mood stabilizer and type of index mood episode.
    Method Stratified Log-rank Test
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.348
    Confidence Interval (2-Sided) 95%
    0.146 to 0.829
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox proportional hazards model, with type of mood stabilizer and type of index mood episode as stratification factors, and treatment group as covariate.
    4. Secondary Outcome
    Title Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
    Description Kaplan Meier estimated survival rate. Relapse is defined as any of the following events accompanied by a YMRS > 16 and/or a MADRS > 16; serious adverse event of worsening disease, or discontinuation by the investigator for lack of efficacy. A hospitalization for a manic, mixed, or depressive episode does meet the criteria for relapse, however does not require an accompanying Y-MRS and/or MADRS score > 16.
    Time Frame Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3

    Outcome Measure Data

    Analysis Population Description
    Randomized sample, n=number of participants at risk at given time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 169 168
    Proportion at Week 0 (n=169, 168)
    1.00
    0.6%
    1.00
    0.6%
    Proportion at Week 4 (n=153, 148)
    0.96
    0.6%
    0.98
    0.6%
    Proportion at Week 8 (n=148, 139)
    0.94
    0.6%
    0.97
    0.6%
    Proportion at Week 12 (n=142, 133)
    0.94
    0.6%
    0.97
    0.6%
    Proportion at Week 16 (n=132, 130)
    0.93
    0.6%
    0.96
    0.6%
    Proportion at Week 20 (n=123, 128)
    0.92
    0.5%
    0.96
    0.6%
    Proportion at Week 24 (n=115, 125)
    0.92
    0.5%
    0.95
    0.6%
    Proportion at Week 28 (n=107, 121)
    0.89
    0.5%
    0.95
    0.6%
    Proportion at Week 32 (n=104, 114)
    0.89
    0.5%
    0.91
    0.5%
    Proportion at Week 36 (n=101, 111)
    0.89
    0.5%
    0.91
    0.5%
    Proportion at Week 40 (n=98, 110)
    0.88
    0.5%
    0.91
    0.5%
    Proportion at Week 44 (n=94, 107)
    0.88
    0.5%
    0.91
    0.5%
    Proportion at Week 48 (n=91, 98)
    0.87
    0.5%
    0.90
    0.5%
    Proportion at Week 52 (n=6, 8)
    0.87
    0.5%
    0.90
    0.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.384
    Comments Stratified Log-rank Test P-value for Equality of Survival Curves
    Method Stratified Log-rank Test
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.733
    Confidence Interval (2-Sided) 95%
    0.364 to 1.479
    Parameter Dispersion Type:
    Value:
    Estimation Comments Cox proportional hazards model, with type of mood stabilizer and type of index mood episode as stratification factors, and treatment group as covariate.
    5. Secondary Outcome
    Title Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
    Description 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 (best) to 60 (worst).
    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)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases (OC) data set; n=number of participants with measurement at given time point.
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 289 383
    Baseline (n=289, 383)
    23.15
    (0.327)
    22.32
    (0.252)
    Change from Baseline at Week 1 (n=277, 371)
    -4.50
    (0.312)
    -4.86
    (0.272)
    Change from Baseline at Week 2 (n=266, 355)
    -7.90
    (0.432)
    -7.82
    (0.351)
    Change from Baseline at Week 4 (n=245, 326)
    -12.11
    (0.454)
    -10.75
    (0.366)
    Change from Baseline at Week 6 (n=221, 305)
    -13.92
    (0.514)
    -13.28
    (0.394)
    Change from Baseline at Week 8 (n=201, 287)
    -16.18
    (0.495)
    -14.84
    (0.406)
    Change from Baseline at Week 12 (n=179, 253)
    -17.74
    (0.528)
    -16.28
    (0.427)
    Change from Baseline at Week 16 (n=138, 193)
    -18.88
    (0.639)
    -17.55
    (0.462)
    Change from Baseline at Week 20 (n=59, 99)
    -20.37
    (1.213)
    -17.64
    (0.741)
    Change from Baseline at Week 24 (n=22, 39)
    -20.82
    (1.550)
    -19.77
    (1.315)
    Change from Baseline at Ph2 endpoint (n=289, 383)
    -14.78
    (0.530)
    -14.32
    (0.429)
    6. Secondary Outcome
    Title Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
    Description 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. 7 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 (best) to 60 (worst).
    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])

    Outcome Measure Data

    Analysis Population Description
    LOCF data set, phase 3 efficacy sample; n=number of participants with measurement at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline (n=164, 162)
    4.03
    (0.285)
    4.06
    (0.280)
    Change at Week 4 (n=160, 162)
    0.47
    (0.342)
    0.53
    (0.332)
    Change at Week 8 (n=164, 162)
    0.91
    (0.353)
    0.23
    (0.346)
    Change at Week 12 (n=164, 162)
    1.53
    (0.415)
    0.43
    (0.408)
    Change at Week 16 (n=164, 162)
    1.74
    (0.433)
    0.35
    (0.425)
    Change at Week 20 (n=164, 162)
    2.29
    (0.472)
    0.38
    (0.463)
    Change at Week 24 (n=164, 162)
    2.42
    (0.492)
    0.24
    (0.483)
    Change at Week 28 (n=164, 162)
    3.02
    (0.547)
    0.40
    (0.537)
    Change at Week 32 (n=164, 162)
    2.72
    (0.526)
    0.39
    (0.516)
    Change at Week 36 (n=164, 162)
    3.04
    (0.538)
    0.26
    (0.528)
    Change at Week 40 (n=164, 162)
    2.82
    (0.542)
    0.11
    (0.532)
    Change at Week 44 (n=164, 162)
    3.19
    (0.558)
    0.27
    (0.548)
    Change at Week 48 (n=164, 162)
    3.15
    (0.575)
    0.07
    (0.564)
    Change at Week 52 (n=164, 162)
    2.93
    (0.576)
    -0.11
    (0.565)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Baseline Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.955
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.02
    Confidence Interval (2-Sided) 95%
    -0.73 to 0.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 4 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.895
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.06
    Confidence Interval (2-Sided) 95%
    -0.83 to 0.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 8 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.144
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.69
    Confidence Interval (2-Sided) 95%
    -1.61 to 0.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 12 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.047
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.10
    Confidence Interval (2-Sided) 95%
    -2.19 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 16 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.39
    Confidence Interval (2-Sided) 95%
    -2.52 to -0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 20 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.91
    Confidence Interval (2-Sided) 95%
    -3.15 to -0.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 24 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -2.18
    Confidence Interval (2-Sided) 95%
    -3.47 to -0.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 28 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -2.62
    Confidence Interval (2-Sided) 95%
    -4.06 to -1.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 32 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -2.33
    Confidence Interval (2-Sided) 95%
    -3.70 to -0.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 36 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -2.78
    Confidence Interval (2-Sided) 95%
    -4.19 to -1.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 40 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -2.71
    Confidence Interval (2-Sided) 95%
    -4.13 to -1.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 44 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -2.92
    Confidence Interval (2-Sided) 95%
    -4.38 to -1.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 48 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -3.08
    Confidence Interval (2-Sided) 95%
    -4.59 to -1.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 52 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Mean change from baseline: ANOVA model, controlling for treatment, mood stabilizer, index mood episode, and baseline value. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -3.04
    Confidence Interval (2-Sided) 95%
    -4.55 to -1.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title 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
    Description The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
    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)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 289 383
    Mean Baseline (n=289, 383)
    10.97
    (0.508)
    11.56
    (0.432)
    Change from Baseline at Week 1 (n=277, 371)
    -1.48
    (0.295)
    -1.51
    (0.256)
    Change from Baseline at Week 2 (n=267, 355)
    -2.23
    (0.352)
    -2.70
    (0.329)
    Change from Baseline at Week 4 (n=245, 326)
    -2.94
    (0.391)
    -3.16
    (0.357)
    Change from Baseline at Week 6 (n=221, 305)
    -2.92
    (0.466)
    -3.69
    (0.383)
    Change from Baseline at Week 8 (n=201, 287)
    -3.07
    (0.460)
    -3.64
    (0.440)
    Change from Baseline at Week 12 (n=179, 253)
    -2.82
    (0.500)
    -3.91
    (0.398)
    Change from Baseline at Week 16 (n=138, 193)
    -2.88
    (0.698)
    -4.28
    (0.425)
    Change from Baseline at Week 20 (n=59, 99)
    -4.68
    (0.944)
    -4.49
    (0.676)
    Change from Baseline at Week 24 (n=22, 39)
    -3.77
    (1.298)
    -5.15
    (1.186)
    Change from Baseline at Ph2 Endpoint (n=289, 383)
    -2.13
    (0.461)
    -2.54
    (0.412)
    8. Secondary Outcome
    Title Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
    Description The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    LOCF data set, phase 3 efficacy sample; N=number of participants evaluated at time point; 4 participants in the Week 4 placebo group were not evaluated.
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Mean Baseline (n=164, 162)
    4.41
    (0.282)
    4.62
    (0.277)
    Mean Change from Baseline at Week 4 (n=160, 162)
    1.92
    (0.421)
    1.42
    (0.411)
    Mean Change from Baseline at Week 8 (n=164, 162)
    2.27
    (0.495)
    1.23
    (0.488)
    Mean Change from Baseline at Week 12 (n=164, 162)
    2.42
    (0.493)
    1.42
    (0.486)
    Mean Change from Baseline at Week 16 (n=164, 162)
    2.12
    (0.505)
    1.27
    (0.498)
    Mean Change from Baseline at Week 20 (n=164, 162)
    2.61
    (0.557)
    1.47
    (0.549)
    Mean Change from Baseline at Week 24 (n=164, 162)
    2.92
    (0.572)
    1.49
    (0.564)
    Mean Change from Baseline at Week 28 (n=164, 162)
    3.14
    (0.601)
    1.64
    (0.594)
    Mean Change from Baseline at Week 32 (n=164, 162)
    3.32
    (0.609)
    1.70
    (0.601)
    Mean Change from Baseline at Week 36 (n=164, 162)
    3.03
    (0.621)
    1.89
    (0.612)
    Mean Change from Baseline at Week 40 (n=164, 162)
    3.18
    (0.626)
    1.65
    (0.618)
    Mean Change from Baseline at Week 44 (n=164, 162)
    3.10
    (0.641)
    1.53
    (0.632)
    Mean Change from Baseline at Week 48 (n=164, 162)
    3.57
    (0.633)
    1.48
    (0.624)
    Mean Change from Baseline at Week 52 (n=164, 162)
    3.47
    (0.640)
    1.46
    (0.632)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Baseline Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.590
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.20
    Confidence Interval (2-Sided) 95%
    -0.54 to 0.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 4 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.371
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.50
    Confidence Interval (2-Sided) 95%
    -1.59 to 0.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 8 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.113
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.04
    Confidence Interval (2-Sided) 95%
    -2.33 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 12 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.128
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.00
    Confidence Interval (2-Sided) 95%
    -2.28 to 0.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 16 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.205
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.85
    Confidence Interval (2-Sided) 95%
    -2.16 to 0.47
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 20 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.125
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.13
    Confidence Interval (2-Sided) 95%
    -2.59 to 0.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 24 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.061
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.43
    Confidence Interval (2-Sided) 95%
    -2.92 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 28 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.060
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.51
    Confidence Interval (2-Sided) 95%
    -3.07 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 32 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.046
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.62
    Confidence Interval (2-Sided) 95%
    -3.21 to -0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 36 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.164
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.15
    Confidence Interval (2-Sided) 95%
    -2.77 to 0.47
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 40 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.066
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.53
    Confidence Interval (2-Sided) 95%
    -3.16 to 0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 44 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.066
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -1.57
    Confidence Interval (2-Sided) 95%
    -3.24 to 0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 48 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -2.08
    Confidence Interval (2-Sided) 95%
    -3.73 to -0.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 52 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.019
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -2.01
    Confidence Interval (2-Sided) 95%
    -3.68 to -0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
    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)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 289 383
    Mean Baseline (BL) (n=289, 383)
    4.25
    (0.040)
    4.08
    (0.036)
    Mean Change from BL to Week 1 (n=275, 370)
    -0.52
    (0.046)
    -0.53
    (0.040)
    Mean Change from BL to Week 2 (n=267, 354)
    -1.05
    (0.061)
    -0.97
    (0.054)
    Mean Change from BL to Week 4 (n=245, 326)
    -1.56
    (0.074)
    -1.31
    (0.059)
    Mean Change from BL to Week 6 (n=219, 305)
    -1.86
    (0.084)
    -1.62
    (0.063)
    Mean Change from BL to Week 8 (n=200, 287)
    -2.17
    (0.081)
    -1.80
    (0.069)
    Mean Change from BL to Week 12 (n=179, 252)
    -2.31
    (0.097)
    -1.99
    (0.078)
    Mean Change from BL to Week 16 (n=138, 193)
    -2.57
    (0.106)
    -2.17
    (0.079)
    Mean Change from BL to Week 20 (n=59, 99)
    -2.71
    (0.181)
    -2.14
    (0.118)
    Mean Change from BL to Week 24 (n=22, 39)
    -2.73
    (0.220)
    -2.38
    (0.186)
    Mean Change from BL to Phase 2 Endpoint(n=289,383)
    -1.90
    (0.085)
    -1.66
    (0.070)
    10. Secondary Outcome
    Title Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Mean Baseline
    1.65
    (0.065)
    1.70
    (0.064)
    Mean Change from Baseline At Week 4 (n=160, 162)
    0.25
    (0.072)
    0.27
    (0.070)
    Mean Change from Baseline At Week 8
    0.32
    (0.080)
    0.21
    (0.079)
    Mean Change from Baseline At Week 12
    0.40
    (0.087)
    0.26
    (0.085)
    Mean Change from Baseline At Week 16
    0.44
    (0.088)
    0.26
    (0.087)
    Mean Change from Baseline At Week 20
    0.51
    (0.095)
    0.29
    (0.094)
    Mean Change from Baseline At Week 24
    0.56
    (0.097)
    0.25
    (0.095)
    Mean Change from Baseline At Week 28
    0.62
    (0.101)
    0.32
    (0.099)
    Mean Change from Baseline At Week 32
    0.61
    (0.102)
    0.30
    (0.100)
    Mean Change from Baseline At Week 36
    0.62
    (0.103)
    0.33
    (0.101)
    Mean Change from Baseline At Week 40
    0.57
    (0.104)
    0.28
    (0.102)
    Mean Change from Baseline At Week 44
    0.64
    (0.105)
    0.30
    (0.103)
    Mean Change from Baseline At Week 48
    0.68
    (0.106)
    0.28
    (0.104)
    Mean Change from Baseline At Week 52
    0.66
    (0.106)
    0.31
    (0.104)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Baseline Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.597
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.05
    Confidence Interval (2-Sided) 95%
    -0.13 to 0.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 4 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.838
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.02
    Confidence Interval (2-Sided) 95%
    -0.17 to 0.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 8 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.291
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.11
    Confidence Interval (2-Sided) 95%
    -0.32 to 0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 12 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.219
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.14
    Confidence Interval (2-Sided) 95%
    -0.37 to 0.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 16 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.133
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.18
    Confidence Interval (2-Sided) 95%
    -0.41 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 20 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.092
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.21
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 24 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.31
    Confidence Interval (2-Sided) 95%
    -0.56 to -0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 28 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.029
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.56 to -0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 32 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.024
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.31
    Confidence Interval (2-Sided) 95%
    -0.57 to -0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 36 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.035
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.56 to -0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 40 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.038
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.56 to -0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 44 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.34
    Confidence Interval (2-Sided) 95%
    -0.62 to -0.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 48 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.39
    Confidence Interval (2-Sided) 95%
    -0.67 to -0.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 52 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.35
    Confidence Interval (2-Sided) 95%
    -0.62 to -0.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from baseline (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
    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)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 289 383
    Mean Baseline (BL) (n=289, 383)
    2.16
    (0.076)
    2.33
    (0.069)
    Mean Change from BL to Week 1 (n=275, 370)
    -0.16
    (0.041)
    -0.19
    (0.040)
    Mean Change from BL to Week 2 (n=267, 354)
    -0.22
    (0.053)
    -0.33
    (0.050)
    Mean Change from BL to Week 4 (n=245, 326)
    -0.29
    (0.058)
    -0.39
    (0.055)
    Mean Change from BL to Week 6 (n=219, 305)
    -0.31
    (0.068)
    -0.43
    (0.061)
    Mean Change from BL to Week 8 (n=200, 287)
    -0.30
    (0.077)
    -0.37
    (0.066)
    Mean Change from BL to Week 12 (n=179, 252)
    -0.17
    (0.077)
    -0.35
    (0.069)
    Mean Change from BL to Week 16 (n=138, 193)
    -0.21
    (0.109)
    -0.36
    (0.078)
    Mean Change from BL to Week 20 (n=59, 99)
    -0.27
    (0.149)
    -0.37
    (0.116)
    Mean Change from BL to Week 24 (n=22, 39)
    -0.23
    (0.227)
    -0.46
    (0.217)
    Mean Change from BL to Phase 2 Endpoint(n=289,383)
    -0.16
    (0.069)
    -0.26
    (0.063)
    12. Secondary Outcome
    Title Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline Mean
    1.43
    (0.049)
    1.47
    (0.048)
    Mean Change from Baseline at Week 4 (n=160, 162)
    0.30
    (0.067)
    0.29
    (0.065)
    Mean Change from Baseline at Week 8
    0.35
    (0.073)
    0.24
    (0.072)
    Mean Change from Baseline at Week 12
    0.37
    (0.077)
    0.23
    (0.076)
    Mean Change from Baseline at Week 16
    0.35
    (0.078)
    0.24
    (0.077)
    Mean Change from Baseline at Week 20
    0.41
    (0.084)
    0.28
    (0.083)
    Mean Change from Baseline at Week 24
    0.44
    (0.086)
    0.27
    (0.085)
    Mean Change from Baseline at Week 28
    0.50
    (0.091)
    0.28
    (0.090)
    Mean Change from Baseline at Week 32
    0.53
    (0.092)
    0.27
    (0.091)
    Mean Change from Baseline at Week 36
    0.49
    (0.092)
    0.32
    (0.091)
    Mean Change from Baseline at Week 40
    0.47
    (0.093)
    0.28
    (0.091)
    Mean Change from Baseline at Week 44
    0.46
    (0.094)
    0.28
    (0.093)
    Mean Change from Baseline at Week 48
    0.50
    (0.094)
    0.27
    (0.092)
    Mean Change from Baseline at Week 52
    0.51
    (0.094)
    0.30
    (0.093)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Baseline Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.588
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.09 to 0.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 4 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.922
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.01
    Confidence Interval (2-Sided) 95%
    -0.18 to 0.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 8 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.266
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.11
    Confidence Interval (2-Sided) 95%
    -0.30 to 0.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 12 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.159
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.14
    Confidence Interval (2-Sided) 95%
    -0.34 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 16 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.305
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.11
    Confidence Interval (2-Sided) 95%
    -0.31 to 0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 20 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.251
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.35 to 0.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 24 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.135
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.17
    Confidence Interval (2-Sided) 95%
    -0.40 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 28 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.22
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 32 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.034
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.26
    Confidence Interval (2-Sided) 95%
    -0.50 to -0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 36 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.174
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.17
    Confidence Interval (2-Sided) 95%
    -0.41 to 0.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 40 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.132
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 44 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.152
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.18
    Confidence Interval (2-Sided) 95%
    -0.42 to 0.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 48 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.060
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.23
    Confidence Interval (2-Sided) 95%
    -0.48 to 0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 52 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.085
    Comments Baseline: ANOVA model, controlling for treatment, mood stabilizer, and index mood episode. Mean change from baseline: ANCOVA model, controlling for treatment, mood stabilizer, index mood episode, baseline value.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.22
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall change from preceding phase items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
    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)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 289 382
    Mean Change from BL to Week 1 (n=274, 369)
    3.15
    (0.055)
    3.09
    (0.049)
    Mean Change from BL to Week 2 (n=265, 353)
    2.61
    (0.062)
    2.58
    (0.054)
    Mean Change from BL to Week 4 (n=245, 325)
    2.14
    (0.060)
    2.24
    (0.056)
    Mean Change from BL to Week 6 (n=219, 305)
    1.95
    (0.065)
    1.97
    (0.056)
    Mean Change from BL to Week 8 (n=200, 287)
    1.73
    (0.062)
    1.80
    (0.055)
    Mean Change from BL to Week 12 (n=179, 252)
    1.66
    (0.074)
    1.65
    (0.053)
    Mean Change from BL to Week 16 (n=138, 193)
    1.54
    (0.082)
    1.61
    (0.056)
    Mean Change from BL to Week 20 (n=59, 99)
    1.69
    (0.161)
    1.68
    (0.087)
    Mean Change from BL to Week 24 (n=22, 39)
    1.64
    (0.214)
    1.67
    (0.181)
    Mean Change from BL to Phase 2 Endpoint(n=289,382)
    1.95
    (0.071)
    1.94
    (0.056)
    14. Secondary Outcome
    Title Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from baseline (mania, depression and overall bipolar illness) items (also a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
    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)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 289 383
    Mean Baseline (BL) (n=289, 383)
    4.22
    (0.040)
    4.06
    (0.035)
    Mean Change from BL to Week 1 (n=275, 370)
    -0.58
    (0.047)
    -0.58
    (0.042)
    Mean Change from BL to Week 2 (n=267, 354)
    -1.15
    (0.064)
    -1.06
    (0.055)
    Mean Change from BL to Week 4 (n=245, 326)
    -1.73
    (0.075)
    -1.45
    (0.062)
    Mean Change from BL to Week 6 (n=219, 305)
    -2.04
    (0.081)
    -1.82
    (0.065)
    Mean Change from BL to Week 8 (n=200, 287)
    -2.40
    (0.076)
    -2.06
    (0.067)
    Mean Change from BL to Week 12 (n=179, 252)
    -2.60
    (0.081)
    -2.27
    (0.071)
    Mean Change from BL to Week 16 (n=138, 193)
    -2.83
    (0.086)
    -2.40
    (0.075)
    Mean Change from BL to Week 20 (n=59, 99)
    -2.93
    (0.162)
    -2.32
    (0.115)
    Mean Change from BL to Week 24 (n=22, 39)
    -2.91
    (0.185)
    -2.56
    (0.163)
    Mean Change from BL to Phase 2 Endpoint(n=289,383)
    -2.21
    (0.079)
    -2.01
    (0.066)
    15. Secondary Outcome
    Title Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Mean Change at Week 4 (n=160, 162)
    2.96
    (0.111)
    3.00
    (0.108)
    Mean Change at Week 8
    3.17
    (0.113)
    2.98
    (0.111)
    Mean Change at Week 12
    3.14
    (0.118)
    3.03
    (0.116)
    Mean Change at Week 16
    3.27
    (0.118)
    2.98
    (0.115)
    Mean Change at Week 20
    3.29
    (0.120)
    3.03
    (0.118)
    Mean Change at Week 24
    3.26
    (0.125)
    2.96
    (0.123)
    Mean Change at Week 28
    3.37
    (0.126)
    3.01
    (0.124)
    Mean Change at Week 32
    3.31
    (0.124)
    3.00
    (0.122)
    Mean Change at Week 36
    3.37
    (0.125)
    2.94
    (0.123)
    Mean Change at Week 40
    3.32
    (0.126)
    2.94
    (0.124)
    Mean Change at Week 44
    3.33
    (0.128)
    2.96
    (0.125)
    Mean Change at Week 48
    3.35
    (0.130)
    2.96
    (0.128)
    Mean Change at Week 52
    3.29
    (0.131)
    2.89
    (0.129)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 4 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.774
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.25 to 0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 8 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.213
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -0.49 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 12 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.465
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.12
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 16 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.068
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.59 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 20 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.095
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.27
    Confidence Interval (2-Sided) 95%
    -0.58 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 24 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.082
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.62 to 0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 28 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.033
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.36
    Confidence Interval (2-Sided) 95%
    -0.69 to -0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 32 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.062
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.31
    Confidence Interval (2-Sided) 95%
    -0.64 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 36 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.43
    Confidence Interval (2-Sided) 95%
    -0.76 to -0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 40 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.37
    Confidence Interval (2-Sided) 95%
    -0.70 to -0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 44 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.029
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.37
    Confidence Interval (2-Sided) 95%
    -0.71 to -0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 48 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -0.74 to -0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 52 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.023
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -0.75 to -0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
    Description 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).
    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)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 289 382
    Mean Change from BL to Week 1 (n=274, 368)
    3.56
    (0.054)
    3.40
    (0.057)
    Mean Change from BL to Week 2 (n=265, 353)
    3.42
    (0.061)
    3.25
    (0.066)
    Mean Change from BL to Week 4 (n=245, 325)
    3.35
    (0.074)
    3.19
    (0.071)
    Mean Change from BL to Week 6 (n=219, 305)
    3.22
    (0.083)
    3.13
    (0.078)
    Mean Change from BL to Week 8 (n=200, 287)
    3.13
    (0.090)
    3.11
    (0.084)
    Mean Change from BL to Week 12 (n=179, 250)
    3.28
    (0.094)
    3.06
    (0.087)
    Mean Change from BL to Week 16 (n=138, 193)
    3.30
    (0.117)
    2.99
    (0.100)
    Mean Change from BL to Week 20 (n=59, 99)
    3.24
    (0.173)
    3.18
    (0.129)
    Mean Change from BL to Week 24 (n=22, 39)
    2.91
    (0.278)
    3.15
    (0.251)
    Mean Change from BL to Phase 2 Endpoint(n=289,382)
    3.30
    (0.080)
    3.26
    (0.075)
    17. Secondary Outcome
    Title Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
    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])

    Outcome Measure Data

    Analysis Population Description
    LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Mean Change at Week 4 (n=160, 162)
    3.46
    (0.102)
    3.56
    (0.100)
    Mean Change at Week 8
    3.55
    (0.103)
    3.52
    (0.101)
    Mean Change at Week 12
    3.51
    (0.106)
    3.45
    (0.104)
    Mean Change at Week 16
    3.52
    (0.108)
    3.45
    (0.107)
    Mean Change at Week 20
    3.58
    (0.111)
    3.53
    (0.109)
    Mean Change at Week 24
    3.63
    (0.112)
    3.54
    (0.110)
    Mean Change at Week 28
    3.65
    (0.116)
    3.52
    (0.114)
    Mean Change at Week 32
    3.69
    (0.116)
    3.49
    (0.114)
    Mean Change at Week 36
    3.62
    (0.119)
    3.52
    (0.117)
    Mean Change at Week 40
    3.55
    (0.120)
    3.47
    (0.118)
    Mean Change at Week 44
    3.52
    (0.121)
    3.49
    (0.120)
    Mean Change at Week 48
    3.58
    (0.121)
    3.44
    (0.120)
    Mean Change at Week 52
    3.56
    (0.122)
    3.44
    (0.120)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 4 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.486
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.09
    Confidence Interval (2-Sided) 95%
    -0.17 to 0.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 8 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.793
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.04
    Confidence Interval (2-Sided) 95%
    -0.30 to 0.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 12 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.665
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.06
    Confidence Interval (2-Sided) 95%
    -0.34 to 0.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 16 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.650
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.07
    Confidence Interval (2-Sided) 95%
    -0.35 to 0.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 20 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.705
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.06
    Confidence Interval (2-Sided) 95%
    -0.34 to 0.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 24 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.572
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.08
    Confidence Interval (2-Sided) 95%
    -0.38 to 0.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 28 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.418
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.12
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 32 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.185
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.20
    Confidence Interval (2-Sided) 95%
    -0.51 to 0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 36 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.536
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.10
    Confidence Interval (2-Sided) 95%
    -0.41 to 0.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 40 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.637
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.07
    Confidence Interval (2-Sided) 95%
    -0.39 to 0.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 44 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.875
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.03
    Confidence Interval (2-Sided) 95%
    -0.34 to 0.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 48 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.378
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.14
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 52 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.474
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.12
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    18. Secondary Outcome
    Title Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
    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)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 289 382
    Mean Change from BL to Week 1 (n=274, 369)
    3.20
    (0.054)
    3.13
    (0.048)
    Mean Change from BL to Week 2 (n=265, 353)
    2.70
    (0.063)
    2.69
    (0.057)
    Mean Change from BL to Week 4 (n=245, 325)
    2.27
    (0.063)
    2.40
    (0.060)
    Mean Change from BL to Week 6 (n=219, 305)
    2.11
    (0.069)
    2.19
    (0.064)
    Mean Change from BL to Week 8 (n=200, 287)
    1.94
    (0.073)
    2.08
    (0.070)
    Mean Change from BL to Week 12 (n=179, 252)
    1.87
    (0.081)
    1.94
    (0.071)
    Mean Change from BL to Week 16 (n=138, 193)
    1.74
    (0.096)
    1.80
    (0.069)
    Mean Change from BL to Week 20 (n=59, 99)
    1.81
    (0.156)
    1.90
    (0.112)
    Mean Change from BL to Week 24 (n=22, 39)
    1.68
    (0.212)
    1.82
    (0.226)
    Mean Change from BL to Phase 2 Endpoint(n=289,382)
    2.26
    (0.082)
    2.37
    (0.072)
    19. Secondary Outcome
    Title Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
    Description Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale [1 to 7], with 1 being very much improved and 7 being very much worse).
    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])

    Outcome Measure Data

    Analysis Population Description
    LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Mean Change at Week 4 (n=160, 162)
    3.17
    (0.113)
    3.27
    (0.110)
    Mean Change at Week 8
    3.36
    (0.118)
    3.22
    (0.116)
    Mean Change at Week 12
    3.34
    (0.122)
    3.27
    (0.120)
    Mean Change at Week 16
    3.45
    (0.121)
    3.22
    (0.119)
    Mean Change at Week 20
    3.53
    (0.125)
    3.31
    (0.122)
    Mean Change at Week 24
    3.60
    (0.127)
    3.31
    (0.125)
    Mean Change at Week 28
    3.65
    (0.130)
    3.31
    (0.127)
    Mean Change at Week 32
    3.63
    (0.130)
    3.29
    (0.128)
    Mean Change at Week 36
    3.61
    (0.132)
    3.28
    (0.130)
    Mean Change at Week 40
    3.54
    (0.133)
    3.24
    (0.131)
    Mean Change at Week 44
    3.57
    (0.135)
    3.28
    (0.132)
    Mean Change at Week 48
    3.63
    (0.136)
    3.26
    (0.134)
    Mean Change at Week 52
    3.58
    (0.138)
    3.25
    (0.135)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 4 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.488
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -0.19 to 0.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 8 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.349
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.15
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 12 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.653
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.07
    Confidence Interval (2-Sided) 95%
    -0.39 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 16 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.141
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.24
    Confidence Interval (2-Sided) 95%
    -0.56 to 0.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 20 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.196
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.22
    Confidence Interval (2-Sided) 95%
    -0.54 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 24 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.088
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.62 to 0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 28 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.047
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.34
    Confidence Interval (2-Sided) 95%
    -0.68 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 32 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.057
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.33
    Confidence Interval (2-Sided) 95%
    -0.67 to 0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 36 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.063
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.33
    Confidence Interval (2-Sided) 95%
    -0.68 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 40 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.091
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.30
    Confidence Interval (2-Sided) 95%
    -0.65 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 44 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.105
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.64 to 0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 48 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.047
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.36
    Confidence Interval (2-Sided) 95%
    -0.72 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Aripiprazole - Placebo; Week 52 Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    Comments Mean change from baseline: ANOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline value. Mean change from preceding phase: ANCOVA controlling for treatment, mood stabilizer, type of index mood episode, baseline CGI-BP.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences, and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Difference
    Estimated Value -0.33
    Confidence Interval (2-Sided) 95%
    -0.69 to 0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    20. Secondary Outcome
    Title Number of Participants Maintaining Remission During Phase 3
    Description Remission is defined as Y-MRS Total Score <=12 and MADRS Total Score <=12.
    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])

    Outcome Measure Data

    Analysis Population Description
    Observed cases data set, Phase 3 Efficacy Sample
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 160 162
    Week 4 (n=160, 162)
    142
    84%
    142
    84.5%
    Week 8 (n=152, 145)
    138
    81.7%
    136
    81%
    Week 12 (n=144, 136)
    133
    78.7%
    126
    75%
    Week 16 (n=138, 131)
    122
    72.2%
    126
    75%
    Week 20 (n=131, 127)
    115
    68%
    117
    69.6%
    Week 24 (n=115, 122)
    107
    63.3%
    119
    70.8%
    Week 28 (n=114, 122)
    100
    59.2%
    115
    68.5%
    Week 32 (n=104, 119)
    99
    58.6%
    112
    66.7%
    Week 36 (n=99, 108)
    91
    53.8%
    104
    61.9%
    Week 40 (n=100, 110)
    93
    55%
    109
    64.9%
    Week 44 (n=91, 109)
    81
    47.9%
    102
    60.7%
    Week 48 (n=92, 102)
    85
    50.3%
    101
    60.1%
    Week 52 (n=89, 97)
    82
    48.5%
    95
    56.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 4
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.910
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.92 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 8
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.300
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.97 to 1.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 12
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.744
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.95 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 16
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.09
    Confidence Interval (2-Sided) 95%
    1.02 to 1.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 20
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.264
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.05
    Confidence Interval (2-Sided) 95%
    0.97 to 1.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 24
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.090
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.05
    Confidence Interval (2-Sided) 95%
    0.99 to 1.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.056
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.08
    Confidence Interval (2-Sided) 95%
    1.00 to 1.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 32
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.756
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.99
    Confidence Interval (2-Sided) 95%
    0.93 to 1.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 36
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.177
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.05
    Confidence Interval (2-Sided) 95%
    0.98 to 1.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 40
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.021
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.07
    Confidence Interval (2-Sided) 95%
    1.01 to 1.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 44
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.216
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.96 to 1.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 48
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.07
    Confidence Interval (2-Sided) 95%
    1.01 to 1.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.083
    Comments Cochran-Mantel-Haenszel General Association Test controlling for mood stabilizer and index mood episode.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.99 to 1.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aripiprazole/Placebo
    21. Secondary Outcome
    Title Proportion of Participants Discontinuing For Any Reason Through Week 52 (During Phase 3)
    Description
    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])

    Outcome Measure Data

    Analysis Population Description
    Randomized Sample
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 169 168
    Number [Proportion of Participants]
    0.473
    0.3%
    0.387
    0.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.132
    Comments
    Method Stratified Log Rank Test
    Comments Stratified Log Rank Test p-value for equality of survival curves.
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 0.78
    Confidence Interval (2-Sided) 95%
    0.56 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    22. Secondary Outcome
    Title Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
    Description Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 292 390
    Deaths
    0
    0%
    0
    0%
    SAEs
    5
    3%
    10
    6%
    Discontinuations due to AEs
    38
    22.5%
    50
    29.8%
    Any AE
    226
    133.7%
    287
    170.8%
    Treatment-related AEs in >=2% of Participants
    188
    111.2%
    233
    138.7%
    Any Extrapyramidal Syndrome-Related AE
    108
    63.9%
    113
    67.3%
    23. Secondary Outcome
    Title Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
    Description AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 292 390
    Any Adverse Event
    226
    133.7%
    287
    170.8%
    Mild/Grade 1
    172
    101.8%
    219
    130.4%
    Moderate/Grade 2
    109
    64.5%
    165
    98.2%
    Severe/Grade 3
    20
    11.8%
    31
    18.5%
    Very Severe/Grade 4
    2
    1.2%
    1
    0.6%
    24. Secondary Outcome
    Title Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
    Description Sinus Tachycardia: ≥120bpm+↑≥15bpm+no current diagnosis of supraventricular (SV) or ventricular tachycardia or atrial fibrillation (AF) or flutter or other rhythm abnormality (RA). Sinus Bradycardia:≥50bpm+↓≥15bpm+no current diagnosis of AF or flutter or other RA. AF:not present→present or present at rate <100bpm pretreatment to present with rate ≥100bpm+increase of ≥15bpm. AV=atrioventricular; PR=PR interval. Other Intraventricular Block: QRS wave ≥0.12 sec+↑≥0.02 sec+no current diagnosis of left or right bundle branch block. Old Infarction not present→present at ≥12 weeks post study entry.
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 292 390
    Tachycardia ≥ 120 bpm and ↑ ≥ 15 bpm
    0
    0%
    2
    1.2%
    Bradycardia ≤ 50 bpm and ↓ 15 bpm
    0
    0%
    4
    2.4%
    Sinus Tachycardia (see description)
    0
    0%
    2
    1.2%
    Sinus Bradycardia (see description)
    0
    0%
    4
    2.4%
    SV Premature Beat - not present → present
    2
    1.2%
    2
    1.2%
    Ventricular Premature Beat - not present → present
    2
    1.2%
    1
    0.6%
    SV Tachycardia not present → present
    0
    0%
    0
    0%
    Ventricular Tachycardia not present → present
    0
    0%
    0
    0%
    Atrial Fibrillation (see description)
    0
    0%
    0
    0%
    Atrial Flutter not present → present
    0
    0%
    0
    0%
    1st Degree AV Block PR ≥0.20 sec and ↑ ≥0.05 sec
    0
    0%
    0
    0%
    2nd Degree AV Block not present → present
    0
    0%
    0
    0%
    3rd Degree AV Block not present → present
    0
    0%
    0
    0%
    Left Bundle Branch Block not present → present
    11
    6.5%
    7
    4.2%
    Right Bundle Branch Block not present → present
    5
    3%
    2
    1.2%
    Pre-excitation Syndrome not present → present
    0
    0%
    0
    0%
    Other Intraventricular Block (see description)
    0
    0%
    0
    0%
    Acute Infarction not present → present
    1
    0.6%
    0
    0%
    Subacute (Recent) Infarction not present → present
    1
    0.6%
    1
    0.6%
    Old Infarction not present → present at >=12 weeks
    0
    0%
    0
    0%
    Myocardial Ischemia not present → present
    0
    0%
    0
    0%
    Symmetrical T-Wave Inversion not present → present
    1
    0.6%
    0
    0%
    QTc Bazett (QTcB) > 450 msec
    15
    8.9%
    8
    4.8%
    QTc Frederica (QTcF) > 450 msec
    5
    3%
    2
    1.2%
    QTcB > 500 msec
    2
    1.2%
    0
    0%
    QTcF > 500 msec
    0
    0%
    0
    0%
    QTcB Change from Baseline > 30 msec
    28
    16.6%
    17
    10.1%
    QTcF Change from Baseline > 30 msec
    21
    12.4%
    11
    6.5%
    QTcB Change from Baseline > 60 msec
    2
    1.2%
    4
    2.4%
    QTcF Change from Baseline > 60 msec
    1
    0.6%
    0
    0%
    25. Secondary Outcome
    Title Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
    Description Heart Rate: increase, ≥120 beats per minute (bpm) and ≥15 relative to baseline (RBL); decrease, ≤50 bpm and ≥15 RBL. Systolic BP: increase, ≥180 mmHg and ≥20 RBL; decrease, ≤90 mmHg and ≥20 RBL. Diastolic BP: increase, ≥105 mmHg and ≥15 RBL; decrease, ≤50 mmHg and ≥15 RBL. For patients missing a baseline value, an on-treatment value was considered potentially clinically relevant if the value meets the criterion value.
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 292 390
    Systolic Blood Pressure (SBP) - Standing Increase
    2
    1.2%
    4
    2.4%
    SBP - Standing Decrease
    0
    0%
    4
    2.4%
    SBP - Supine Increase
    1
    0.6%
    6
    3.6%
    SBP - Supine Decrease
    2
    1.2%
    4
    2.4%
    SBP - Sitting Increase
    0
    0%
    0
    0%
    SBP - Sitting Decrease
    1
    0.6%
    0
    0%
    Diastolic Blood Pressure (DBP) - Standing Increase
    4
    2.4%
    7
    4.2%
    DBP - Standing Decrease
    0
    0%
    3
    1.8%
    DBP - Supine Increase
    2
    1.2%
    5
    3%
    DBP - Supine Decrease
    1
    0.6%
    3
    1.8%
    DBP - Sitting Increase
    0
    0%
    3
    1.8%
    DBP - Sitting Decrease
    0
    0%
    0
    0%
    Heart Rate - Standing Increase
    0
    0%
    2
    1.2%
    Heart Rate - Standing Decrease
    1
    0.6%
    0
    0%
    Heart Rate - Supine Increase
    0
    0%
    1
    0.6%
    Heart Rate - Supine Decrease
    1
    0.6%
    1
    0.6%
    Heart Rate - Sitting Increase
    0
    0%
    1
    0.6%
    Heart Rate - Sitting Decrease
    0
    0%
    0
    0%
    Weight - Increase
    26
    15.4%
    46
    27.4%
    Weight - Decrease
    15
    8.9%
    6
    3.6%
    26. Secondary Outcome
    Title Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
    Description ULN=upper limit of normal; HDL=high density lipoprotein; LDL=low density lipoprotein. Values for ULN are provided by the lab in the database and could be different for each individual patient based on characteristics such as age, gender, or other patient attributes.
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 292 390
    Alkaline Phosphatase ≥ 3 x ULN (n=272, 360)
    0
    0%
    0
    0%
    Alanine Aminotransferase ≥ 3 x ULN (n=273, 359)
    3
    1.8%
    6
    3.6%
    Aspartate Aminotransferase ≥ 3 x ULN (n=273, 359)
    0
    0%
    3
    1.8%
    Blood Urea Nitrogen ≥ 30 mg/dL (n=225, 312)
    0
    0%
    7
    4.2%
    Creatine Kinase >= 3 x ULN (n=273, 360)
    6
    3.6%
    20
    11.9%
    Creatinine ≥ 2.0 mg/dL (n=271, 359)
    1
    0.6%
    1
    0.6%
    Lactate Dehydrogenase >= 3 x ULN (n=270, 358)
    0
    0%
    0
    0%
    Prolactin > ULN (n=231, 306)
    10
    5.9%
    9
    5.4%
    Bilirubin Total ≥ 2.0 mg/dL (n=n=272, 360)
    2
    1.2%
    1
    0.6%
    Uric Acid ≥10.5mg/dL(M)/≥8.5mg/dL(F) (n=273, 360)
    10
    5.9%
    7
    4.2%
    Total Calcium ≤8.2 mg/dL or ≥12 mg/dL (n=273, 360)
    2
    1.2%
    13
    7.7%
    Chloride Serum ≤90 mEq/L or ≥118 mEq/L(n=273, 360)
    1
    0.6%
    4
    2.4%
    Potassium Serum ≤2.5 mEq/L/≥6.5 mEq/L(n=271, 358)
    0
    0%
    1
    0.6%
    Sodium Serum ≤126 mEq/L/≥156 mEq/L (n=273, 360)
    0
    0%
    2
    1.2%
    Hematocrit ≤37(M)/≤32(F)+3 pts↓from BL(n=272, 358)
    5
    3%
    4
    2.4%
    Hemoglobin ≤11.5 g/dL(M)/≤9.5 g/dL(F) (n=272, 359)
    8
    4.7%
    3
    1.8%
    Leukocytes <=2800 mm^3 or >=16000 mm^3(n=272, 358)
    9
    5.3%
    2
    1.2%
    Eosinophils Relative (Calculated) ≥10%(n=272, 358)
    9
    5.3%
    12
    7.1%
    Neutrophils Relative (Calculated) ≤15%(n=272, 358)
    0
    0%
    1
    0.6%
    Platelets ≤75,000 mm^3/≥700,000 mm^3 (n=268, 357)
    1
    0.6%
    0
    0%
    Urine Glucose-any glucose in the urine(n=269,357)
    7
    4.1%
    13
    7.7%
    Urine Protein Increase of ≥ 2 units (n=269, 357)
    10
    5.9%
    6
    3.6%
    Glucose (Non-fasting) ≥200 mg/dL (n=78, 89)
    2
    1.2%
    3
    1.8%
    Glucose (Fasting) ≥ 126 mg/dL (n=251, 332)
    42
    24.9%
    28
    16.7%
    HDL Cholesterol (combined) <40 mg/dL (n=273, 360)
    94
    55.6%
    131
    78%
    HDL Cholesterol (Fasting) <40 mg/dL (n=252, 332)
    85
    50.3%
    117
    69.6%
    HDL Cholesterol (Non-fasting) <40 mg/dL (n=79, 91)
    20
    11.8%
    31
    18.5%
    Total Cholesterol (Combined) ≥240 mg/dL(n=273,360)
    37
    21.9%
    53
    31.5%
    Total Cholesterol (Fasting) ≥240 mg/dL (n=252,332)
    32
    18.9%
    49
    29.2%
    Total Cholesterol (Non-fasting) ≥240mg/dL(n=79,92)
    7
    4.1%
    11
    6.5%
    LDL Cholesterol (Combined) ≥160 mg/dL (n=273, 360)
    30
    17.8%
    47
    28%
    LDL Cholesterol (Fasting) ≥160 mg/dL (n=252, 332)
    28
    16.6%
    44
    26.2%
    LDL Cholesterol (Non-fasting) ≥160 mg/dL (n=79,91)
    4
    2.4%
    8
    4.8%
    Triglycerides (Combined) ≥ 200 mg/dL (n=273, 360)
    88
    52.1%
    108
    64.3%
    Triglycerides (Non-Fasting) ≥ 200 mg/dL (n=79, 93)
    25
    14.8%
    33
    19.6%
    Triglycerides (Fasting) ≥ 200 mg/dL (n=252, 332)
    73
    43.2%
    85
    50.6%
    27. Secondary Outcome
    Title Median Baseline and Change From Baseline in ECG Measurements During Phase 2
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n= participants with measurement at time point.
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 223 285
    QTcBazett (QTcB) at Baseline (n=223, 285)
    415.0
    412.0
    QTcB Change at Phase 2 Endpoint (n=223, 285)
    4.0
    -8.0
    QTcB (0.33) at Baseline (n=223, 284)
    403.0
    400.0
    QTcB(0.33) Change at Phase 2 Endpoint (n=223, 284)
    4.0
    -6.0
    PR at Baseline (n=222, 284)
    154.0
    150.0
    PR Change at Phase 2 Endpoint (n=222, 284)
    2.0
    -2.0
    RR at Baseline (n=223, 284)
    845.0
    870.0
    RR Change at Phase 2 Endpoint (n=223, 284)
    0.0
    0.0
    QRS at Baseline (n=223, 284)
    90.0
    90.0
    QRS Change at Phase 2 Endpoint (n=223, 284)
    0.0
    -1.0
    28. Secondary Outcome
    Title Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n= participants with measurement at time point.
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 286 372
    Supine Heart Rate (HR) at Baseline (n=286, 372)
    76.0
    74.0
    Supine HR Change at Phase 2 Endpoint (n=286, 372)
    0.0
    0.0
    Sitting Heart Rate (HR) at Baseline (n=51, 67)
    78.0
    82.0
    Sitting HR Change at Phase 2 Endpoint (n=51, 67)
    2.0
    -2.0
    Standing HR at Baseline (n=260, 333)
    78.0
    78.0
    Standing HR Change at Phase 2 Endpoint(n=260, 333)
    0.0
    0.0
    29. Secondary Outcome
    Title Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n= participants with measurement at time point.
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 286 372
    Supine Systolic BP (SBP) at Baseline (n=286, 372)
    120.0
    120.0
    Supine SBP Change at Phase 2 Endpoint (n=286, 372)
    0.0
    0.0
    Supine Diastolic BP (DBP) at Baseline(n=286, 372)
    76.0
    77.5
    Supine DBP Change at Phase 2 Endpoint (n=286, 372)
    0.0
    0.0
    Sitting SBP at Baseline (n=51, 67)
    120.0
    120.0
    Sitting SBP Change at Phase 2 Endpoint (n=51, 67)
    0.0
    0.0
    Sitting DBP at Baseline (n=51, 67)
    78.0
    80.0
    Sitting DBP Change at Phase 2 Endpoint (n=51, 67)
    0.0
    0.0
    Standing SBP at Baseline (n=260, 333)
    120.0
    120.0
    Standing SBP Change at Phase 2 Endpoint(n=260,333)
    0.0
    0.0
    Standing DBP at Baseline (n=260, 333)
    78.5
    78.0
    Standing DBP Change at Phase 2 Endpoint(n=260,333)
    0.0
    0.0
    30. Secondary Outcome
    Title Median Baseline and Change From Baseline in Weight Vital Sign Measurements At Phase 2 Endpoint
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, participants with measurement at time point.
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 218 294
    Weight at Baseline
    76.2
    76.4
    Weight Change at Phase 2 Endpoint
    0.9
    1.5
    31. Secondary Outcome
    Title Median Baseline and Change From Baseline in Body Mass Index (BMI) Vital Sign Measurements at Phase 2 Endpoint
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, participants with measurement at time point.
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 218 294
    BMI at Baseline
    26.9
    27.2
    BMI Change at Phase 2 Endpoint
    0.3
    0.5
    32. Secondary Outcome
    Title Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    ALP (n=265, 347)
    72.0
    64.0
    ALT (n=266, 346)
    20.0
    17.0
    AST (n=266, 346)
    19.0
    20.0
    CK (n=266, 347)
    79.0
    91.0
    LD (n=262, 342)
    168.0
    173.0
    33. Secondary Outcome
    Title 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
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    ALP (n=265, 347)
    -2.0
    -2.0
    ALT (n=266, 346)
    0.0
    2.0
    AST (n=266, 346)
    0.0
    1.0
    CK (n=266, 347)
    -1.0
    -2.0
    LD (n=262, 342)
    -3.0
    -1.0
    34. Secondary Outcome
    Title Median Baseline and Change From Baseline in Heart Rate Measurements During Phase 2
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n= participants with measurement at time point.
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 223 285
    Heart Rate at Baseline (n=223, 284)
    71.0
    69.0
    Heart Rate Change at Phase 2 Endpoint (n=223, 284)
    0.0
    0
    35. Secondary Outcome
    Title 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
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    BUN (n=223, 302)
    11.0
    13.0
    TC (n=245, 318)
    182.0
    174.0
    Creatine (n=263, 343)
    0.900
    0.900
    Glucose (n=242, 312)
    92.0
    89.0
    HDL-C (n=245, 318)
    47.0
    45.0
    LDL-C (n=245, 318)
    105.0
    101.0
    Bilirubin (n=265, 347)
    0.40
    0.40
    Triglycerides (n=245, 318)
    112.0
    114.0
    Uric Acid (n=266, 347)
    5.55
    5.10
    36. Secondary Outcome
    Title 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
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    BUN (n=223, 302)
    0.0
    0.0
    TC (n=245, 318)
    -1.0
    4.5
    Creatine (n=263, 343)
    0.0
    0.0
    Glucose (n=242, 312)
    2.0
    1.0
    HDL-C (n=245, 318)
    -1.0
    1.0
    LDL-C (n=245, 318)
    -4.0
    2.0
    Bilirubin (n=265, 347)
    0.0
    0.0
    Triglycerides (n=245, 318)
    2.0
    3.0
    Uric Acid (n=266, 347)
    -0.10
    0.10
    37. Secondary Outcome
    Title Median Baseline Eosinophils (Relative) and Neutrophils (Relative)
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    Eosinophils, relative (n=266, 347)
    2.50
    2.20
    Neutrophils, relative (n=266, 346)
    67.60
    58.10
    38. Secondary Outcome
    Title Median Change From Baseline in Eosinophils (Relative) and Neutrophils (Relative)
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample; n=number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    Eosinophils, relative (n=266, 347)
    -0.40
    -0.20
    Neutrophils, relative (n=266, 346)
    0.25
    0.60
    39. Secondary Outcome
    Title Median Baseline Hemoglobin
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    Median (Full Range) [g/dL]
    13.75
    13.80
    40. Secondary Outcome
    Title Median Change From Baseline in Hemoglobin
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    Median (Full Range) [g/dL]
    0.05
    0.10
    41. Secondary Outcome
    Title Median Baseline Hematocrit
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 265 344
    Median (Full Range) [percentage of total blood volume]
    41.30
    41.10
    42. Secondary Outcome
    Title Median Change From Baseline in Hematocrit
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 265 344
    Median (Full Range) [percentage of total blood volume]
    0.30
    0.20
    43. Secondary Outcome
    Title Median Baseline Homeostasis Model Assessment 2 (HOMA2)-Percent Beta
    Description HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 58 44
    Median (Full Range) [percentage of 'normal function']
    99.95
    118.70
    44. Secondary Outcome
    Title Median Baseline Homeostasis Model Assessment 2 HOMA2-Insulin Resistance (IR)
    Description HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 58 44
    Median (Full Range) [proportion of 'normal function']
    1.14
    1.42
    45. Secondary Outcome
    Title Median Change From Baseline in Homeostasis Model Assessment 2(HOMA2)-Percent Beta at Phase 2 Endpoint
    Description HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 58 44
    Median (Full Range) [percentage of 'normal function']
    7.70
    17.05
    46. Secondary Outcome
    Title Median Change From Baseline in HOMA2 Model Assesses Insulin Resistance (HOMA2-IR) at Phase 2 Endpoint
    Description HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 58 44
    Median (Full Range) [proportion of 'normal function']
    0.09
    0.15
    47. Secondary Outcome
    Title Median Baseline Platelet Count
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 262 345
    Median (Full Range) [x10^9 c/L]
    297.0
    226.0
    48. Secondary Outcome
    Title Median Change From Baseline in Platelet Count at Phase 2 Endpoint
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 262 345
    Median (Full Range) [x10^9 c/L]
    -4.0
    -2.0
    49. Secondary Outcome
    Title Median Baseline Prolactin
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 6 8
    Median (Full Range) [ng/dL]
    10.0
    9.5
    50. Secondary Outcome
    Title Median Change From Baseline in Prolactin at Phase 2 Endpoint
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 6 8
    Median (Full Range) [ng/dL]
    -2.5
    -3.0
    51. Secondary Outcome
    Title Median Baseline Leukocytes
    Description
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    Median (Full Range) [x10^3 c/L]
    8.350
    6.800
    52. Secondary Outcome
    Title Median Change From Baseline in Leukocytes at Phase 2 Endpoint
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 266 347
    Median (Full Range) [x10^3 c/L]
    -0.100
    -0.200
    53. Secondary Outcome
    Title Baseline Abnormal Involuntary Movement Scale (AIMS)
    Description The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 220 295
    Mean (Standard Error) [units on a scale]
    0.10
    (0.042)
    0.08
    (0.028)
    54. Secondary Outcome
    Title Unadjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) at Phase 2 Endpoint
    Description The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 220 295
    Mean (Standard Error) [units on a scale]
    0.05
    (0.056)
    0.04
    (0.043)
    55. Secondary Outcome
    Title Baseline in Simpson-Angus Scale (SAS) Total Score
    Description The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50.(lower score=less severe). Negative change scores indicate improvement.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 221 295
    Mean (Standard Error) [units on a scale]
    10.28
    (0.054)
    10.30
    (0.048)
    56. Secondary Outcome
    Title Unadjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score at Phase 2 Endpoint
    Description The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50(lower score=less severe). Negative change scores indicate improvement.
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 221 295
    Mean (Standard Error) [units on a scale]
    0.44
    (0.118)
    0.15
    (0.073)
    57. Secondary Outcome
    Title Baseline in Barnes Akathisia Global Clinical Assessment
    Description The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 221 295
    Mean (Standard Error) [units on a scale]
    0.09
    (0.022)
    0.14
    (0.024)
    58. Secondary Outcome
    Title Unadjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Phase 2 Endpoint
    Description The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
    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)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 Safety Sample, number of participants with evaluation at time point
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 221 295
    Mean (Standard Error) [units on a scale]
    0.14
    (0.043)
    0.07
    (0.039)
    59. Secondary Outcome
    Title Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3
    Description Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
    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])

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 166 167
    Deaths
    1
    0.6%
    1
    0.6%
    Treatment-Emergent SAEs
    8
    4.7%
    11
    6.5%
    Treatment-Emergent AEs
    105
    62.1%
    105
    62.5%
    Treatment-Emergent AEs in >=2% of Participants
    49
    29%
    62
    36.9%
    Treatment-Emergent AEs Leading to Discontinuation
    15
    8.9%
    19
    11.3%
    60. Secondary Outcome
    Title Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
    Description AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
    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])

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample; (n=number of participants in sample for each category)
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 166 167
    Participants <= 50 Years (n=132, 131)
    81
    47.9%
    84
    50%
    Participants >50 Years (n=34, 36)
    24
    14.2%
    21
    12.5%
    Male Participants (n=70, 81)
    45
    26.6%
    47
    28%
    Female Participants (n=96, 86)
    60
    35.5%
    58
    34.5%
    White Participants (n=63, 74)
    63
    37.3%
    74
    44%
    Non-White Participants (n=42, 31)
    42
    24.9%
    31
    18.5%
    Participants with Mild/Grade 1 AE
    75
    44.4%
    75
    44.6%
    Participants with Moderate/Grade 2 AE
    53
    31.4%
    55
    32.7%
    Participants with Severe/Grade 3 AE
    11
    6.5%
    9
    5.4%
    Participants with Very Severe/Grade 4 AE
    1
    0.6%
    2
    1.2%
    61. Secondary Outcome
    Title Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
    Description Heart Rate: increase, ≥120 beats per minute (bpm) and ≥15 relative to baseline (RBL); decrease, ≤50 bpm and ≥15 RBL. Systolic BP: increase, ≥180 mmHg and ≥20 RBL; decrease, ≤90 mmHg and ≥20 RBL. Diastolic BP: increase, ≥105 mmHg and ≥15 RBL; decrease, ≤50 mmHg and ≥15 RBL. For patients missing a baseline value, an on-treatment value was considered potentially clinically relevant if the value meets the criterion value.
    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])

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample; n= number of participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 166 167
    SBP- Standing Increase (n=145, 147)
    0
    0%
    0
    0%
    SBP- Standing Decrease (n=145, 147)
    2
    1.2%
    1
    0.6%
    SBP- Supine Increase (n=165, 164)
    0
    0%
    0
    0%
    SBP- Supine Decrease (n=165, 164)
    2
    1.2%
    2
    1.2%
    SBP- Sitting Increase (n=41, 47)
    0
    0%
    0
    0%
    SBP- Sitting Decrease (n=41, 47)
    0
    0%
    1
    0.6%
    DBP- Standing Increase (n=145, 147)
    5
    3%
    1
    0.6%
    DBP- Standing Decrease (n=145, 147)
    0
    0%
    2
    1.2%
    DBP- Supine Increase (n=165, 164)
    4
    2.4%
    3
    1.8%
    DBP- Supine Decrease (n=165, 164)
    1
    0.6%
    2
    1.2%
    DBP- Sitting Increase (n=41, 47)
    1
    0.6%
    0
    0%
    DBP- Sitting Decrease (n=41, 47)
    0
    0%
    0
    0%
    HR- Standing Increase (n=145, 147)
    1
    0.6%
    1
    0.6%
    HR- Standing Decrease (n=145, 147)
    2
    1.2%
    0
    0%
    HR- Supine Increase (n=165, 164)
    0
    0%
    0
    0%
    HR- Supine Decrease (n=165, 164)
    1
    0.6%
    1
    0.6%
    HR- Sitting Increase (n=41, 47)
    0
    0%
    0
    0%
    HR- Sitting Decrease (n=41, 47)
    0
    0%
    1
    0.6%
    62. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Systolic BP During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, Week 52 Last Observation Carried Forward (LOCF)
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 162 161
    Baseline
    120.0
    120.0
    Change from Baseline at Week 52 (LOCF)
    0.0
    0.0
    Highest Change Value During Phase 3
    8.0
    6.0
    Lowest Change Value During Phase 3
    -6.0
    -8.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.640
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.423
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.297
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.707
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    63. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Diastolic BP During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, Week 52 Last Observation Carried Forward (LOCF)
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 162 161
    Baseline
    78.0
    79.0
    Change from Baseline at Week 52 (LOCF)
    0.0
    0.0
    Highest Change Value During Phase 3
    5.5
    6.0
    Lowest Change Value During Phase 3
    -6.0
    -6.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.656
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.045
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.532
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.578
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    64. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Heart Rate During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, Week 52 Last Observation Carried Forward (LOCF)
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 162 161
    Baseline
    74.0
    74.0
    Change from Baseline at Week 52 (LOCF)
    0.0
    1.0
    Highest Change Value During Phase 3
    7.5
    8.0
    Lowest Change Value During Phase 3
    -5.5
    -5.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.619
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.868
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.284
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.481
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    65. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Systolic BP During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 33 33
    Baseline
    120.0
    120.0
    Change from Baseline at Week 52 (LOCF)
    2.0
    0.0
    Highest Change Value During Phase 3
    8.0
    4.0
    Lowest Change Value During Phase 3
    -3.0
    -6.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.184
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.206
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    66. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Diastolic BP During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 33 33
    Baseline
    80.0
    80.0
    Change from Baseline at Week 52 (LOCF)
    0.0
    -2.0
    Highest Change Value During Phase 3
    4.0
    0.0
    Lowest Change Value During Phase 3
    -4.0
    -4.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.142
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.110
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.542
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    67. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Heart Rate During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 33 33
    Baseline
    78.0
    76.0
    Change from Baseline at Week 52 (LOCF)
    -4.0
    -2.0
    Highest Change Value During Phase 3
    3.0
    4.0
    Lowest Change Value During Phase 3
    -4.0
    -2.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.916
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.707
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.665
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.757
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    68. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Systolic BP During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 143 143
    Baseline
    120.0
    120.0
    Change from Baseline at Week 52 (LOCF)
    0.0
    0.0
    Highest Change Value During Phase 3
    8.0
    6.0
    Lowest Change Value During Phase 3
    -7.0
    -8.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.871
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.362
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.295
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.519
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    69. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Diastolic BP During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 143 143
    Baseline
    78.0
    78.0
    Change from Baseline at Week 52 (LOCF)
    0.0
    0.0
    Highest Change Value During Phase 3
    6.0
    6.0
    Lowest Change Value During Phase 3
    -6.0
    -6.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.935
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.174
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.527
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.753
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    70. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Heart Rate During Phase 3
    Description
    Time Frame Baseline, During Phase 3 (for highest/lowest values), Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 143 143
    Baseline
    78.0
    78.0
    Change from Baseline at Week 52 (LOCF)
    0.0
    1.0
    Highest Change Value During Phase 3
    6.0
    7.0
    Lowest Change Value During Phase 3
    -7.0
    -6.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Baseline Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.850
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.709
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.326
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison; Aripiprazole/Placebo
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.201
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    71. Secondary Outcome
    Title Baseline and Adjusted Mean Change From Baseline in Weight
    Description
    Time Frame Baseline, Weeks 12, 24, 36, 52, During Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Observed Cases Data Set, Week 52 LOCF; n= number of participants with value at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 161 160
    Baseline (n=161, 160)
    81.33
    (1.80)
    80.22
    (1.79)
    Change at Week 12 (n=129, 121)
    -1.00
    (0.67)
    0.28
    (0.69)
    Change at Week 24 (n=111, 118)
    0.35
    (0.53)
    0.13
    (0.51)
    Change at Week 36 (n=89, 98)
    0.64
    (0.65)
    0.59
    (0.60)
    Change at Week 52 (n=85, 95)
    1.66
    (0.78)
    1.61
    (0.72)
    Change at Week 52 (LOCF) (n=161, 160)
    0.60
    (0.49)
    1.07
    (0.49)
    Highest Change Value (n=161, 160)
    2.39
    (0.42)
    2.35
    (0.42)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 (LOCF) Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.491
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.47
    Confidence Interval (2-Sided) 95%
    -0.87 to 1.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.945
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.04
    Confidence Interval (2-Sided) 95%
    -1.21 to 1.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    72. Secondary Outcome
    Title Number of Participants Showing Relevant Weight Gain During Phase 3
    Description Relevant weight gain: >=7% increase from baseline
    Time Frame Weeks 12, 24, 36, 52, 52 (LOCF), and throughout Phase 3 (for 'at any time' assessment)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample; n=number of participants with measurement at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 163 164
    Weight Gain at Week 12 (n=129, 121)
    3
    1.8%
    6
    3.6%
    Weight Gain at Week 24 (n=111, 118)
    6
    3.6%
    11
    6.5%
    Weight Gain at Week 36 (n=89, 98)
    16
    9.5%
    12
    7.1%
    Weight Gain at Week 52 (n=85, 95)
    16
    9.5%
    18
    10.7%
    Weight Gain at Week 52 (LOCF) (n=161, 160)
    19
    11.2%
    22
    13.1%
    Weight Gain at Any Time (n=163, 164)
    23
    13.6%
    29
    17.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 12 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.279
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 24 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.247
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 36 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.329
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.928
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 (LOCF) Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.584
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    0.66 to 2.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments "At Any Time" Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.369
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.26
    Confidence Interval (2-Sided) 95%
    0.76 to 2.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    73. Secondary Outcome
    Title Number of Participants Showing Relevant Weight Loss During Phase 3
    Description Relevant weight loss: >=7% decrease from baseline
    Time Frame Weeks 12, 24, 36, 52, 52 (LOCF), and throughout Phase 3 (for 'at any time' assessment)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample; n=number of participants with measurement at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 163 164
    Weight Gain at Week 12 (n=129, 121)
    5
    3%
    6
    3.6%
    Weight Gain at Week 24 (n=111, 118)
    7
    4.1%
    8
    4.8%
    Weight Gain at Week 36 (n=89, 98)
    7
    4.1%
    8
    4.8%
    Weight Gain at Week 52 (n=85, 95)
    7
    4.1%
    5
    3%
    Weight Gain at Week 52 (LOCF) (n=161, 160)
    13
    7.7%
    10
    6%
    Weight Gain at Any Time (n=163, 164)
    18
    10.7%
    18
    10.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 12 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.685
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 24 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.792
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 36 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.805
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.533
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 (LOCF) Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.545
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 0.78
    Confidence Interval (2-Sided) 95%
    0.35 to 1.74
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments "At Any Time" Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.987
    Comments CMH General Association Test controlling for mood stabilizer.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Ratio (RR)
    Estimated Value 1.01
    Confidence Interval (2-Sided) 95%
    0.54 to 1.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    74. Secondary Outcome
    Title Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
    Description
    Time Frame Baseline, Week 12, Week 24, Week 36, Week 52, Week 52 (LOCF), During Phase 3 (for lowest/highest values)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample; n=number of participants with measurement at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 161 160
    Baseline (n=161, 160)
    27.0
    27.9
    Change at Week 12 (n=129, 121)
    0.0
    0.2
    Change at Week 24 (n=111, 118)
    0.1
    0.2
    Change at Week 36 (n=89, 98)
    0.1
    0.4
    Change at Week 52 (n=85, 95)
    0.5
    0.7
    Change at Week 52 (LOCF) (n=161, 160)
    0.2
    0.5
    Highest Value During Phase 3 (n=161, 160)
    0.4
    0.7
    Lowest Value During Phase 3 (n=161, 160)
    -0.4
    -0.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.646
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model on the rank of the change from baseline, controlling for treatment, mood stabilizer, and the rank of baseline is used for change from baseline.
    Method ANOVA/ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 12 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model on the rank of the change from baseline, controlling for treatment, mood stabilizer, and the rank of baseline is used for change from baseline.
    Method ANOVA/ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 24 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.485
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model on the rank of the change from baseline, controlling for treatment, mood stabilizer, and the rank of baseline is used for change from baseline.
    Method ANOVA/ANCOVA
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 36 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.325
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model on the rank of the change from baseline, controlling for treatment, mood stabilizer, and the rank of baseline is used for change from baseline.
    Method ANOVA/ANCOVA
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.374
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model on the rank of the change from baseline, controlling for treatment, mood stabilizer, and the rank of baseline is used for change from baseline.
    Method ANOVA/ANCOVA
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 (LOCF) Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.064
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model on the rank of the change from baseline, controlling for treatment, mood stabilizer, and the rank of baseline is used for change from baseline.
    Method ANOVA/ANCOVA
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.310
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model on the rank of the change from baseline, controlling for treatment, mood stabilizer, and the rank of baseline is used for change from baseline.
    Method ANOVA/ANCOVA
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value Treatment Comparison
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.046
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model on the rank of the change from baseline, controlling for treatment, mood stabilizer, and the rank of baseline is used for change from baseline.
    Method ANOVA/ANCOVA
    Comments
    75. Secondary Outcome
    Title Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
    Description ULN=upper limit of normal; Hb=hemoglobin
    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])

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample; n=number of participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 166 167
    Alkaline Phosphatase ≥ 3 x ULN (n=166,165)
    2
    1.2%
    0
    0%
    Alanine Aminotransferase ≥ 3 x ULN (n=166,165)
    3
    1.8%
    3
    1.8%
    Aspartate Aminotransferase ≥ 3 x ULN (n=166,165)
    0
    0%
    0
    0%
    Blood Urea Nitrogen ≥ 30 mg/dL (n=139, 138)
    3
    1.8%
    1
    0.6%
    Creatine Kinase (n=166,165)
    8
    4.7%
    6
    3.6%
    Creatinine ≥ 2.0 mg/dL (n=166,164)
    0
    0%
    1
    0.6%
    Lactate Dehydrogenase (n=166,164)
    0
    0%
    0
    0%
    Prolactin > ULN (n=163, 158)
    14
    8.3%
    14
    8.3%
    Bilirubin Total ≥ 2.0 mg/dL (n=166, 165)
    2
    1.2%
    3
    1.8%
    Uric Acid≥10.5 mg/dL(M)/≥ 8.5 mg/dL(F)(n=166, 165)
    4
    2.4%
    7
    4.2%
    Total Calcium ≤8.2 mg/dL or ≥12 mg/dL (n=166, 165)
    4
    2.4%
    7
    4.2%
    Chloride Serum ≤90 mEq/L or ≥118 mEq/L(n=166, 165)
    1
    0.6%
    1
    0.6%
    Potassium Serum ≤2.5 or ≥6.5 mEq/L (n=166, 164)
    0
    0%
    3
    1.8%
    Sodium Serum ≤126 or ≥156 mEq/L (n=166, 165)
    1
    0.6%
    1
    0.6%
    Hematocrit ≤37(M) or ≤32(F)3 poi (n=166, 164)
    7
    4.1%
    8
    4.8%
    Hb ≤11.5 g/dl (M) / ≤9.5 g/dL (F) (n=166, 164)
    2
    1.2%
    4
    2.4%
    Leukocytes (n=166, 164)
    5
    3%
    3
    1.8%
    Eosinophils Relative (Calculated) ≥10 (n=166, 164)
    6
    3.6%
    11
    6.5%
    Neutrophils Relative (Calculated) ≤15 (n=166, 164)
    0
    0%
    0
    0%
    Platelet Count (n=165, 162)
    0
    0%
    0
    0%
    Urine Glucose (n=166, 165)
    8
    4.7%
    8
    4.8%
    Urine Protein (n=166, 165)
    5
    3%
    4
    2.4%
    Glucose (non-fasting) (n=38, 28)
    1
    0.6%
    0
    0%
    Glucose (fasting) (n=159, 158)
    26
    15.4%
    27
    16.1%
    HDL Cholesterol (combined) (n=166, 165)
    81
    47.9%
    91
    54.2%
    HDL Cholesterol (fasting) (n=160, 159)
    76
    45%
    88
    52.4%
    HDL Cholesterol (non-fasting) (n=38, 27)
    20
    11.8%
    11
    6.5%
    Total Cholesterol (combined) (n=166, 165)
    28
    16.6%
    38
    22.6%
    Total Cholesterol (fasting) (n=160, 159)
    27
    16%
    35
    20.8%
    Total Cholesterol (non-fasting) (n=38, 27)
    3
    1.8%
    7
    4.2%
    LDL Cholesterol (combined) (n=166, 165)
    24
    14.2%
    23
    13.7%
    LDL Cholesterol (fasting) (n=160, 159)
    24
    14.2%
    22
    13.1%
    LDL Cholesterol (non-fasting) (n=38, 27)
    1
    0.6%
    3
    1.8%
    Triglycerides (combined) (n=166, 165)
    59
    34.9%
    67
    39.9%
    Triglycerides (non-fasting) (n=38, 28)
    16
    9.5%
    15
    8.9%
    Triglycerides (fasting) (n=160,159)
    48
    28.4%
    63
    37.5%
    76. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Alkaline Phosphatase (ALP), Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    60.5
    62.5
    Change at Week 52 LOCF
    1.0
    0.0
    Highest Value of Change in Phase 3
    8.0
    7.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline ALP
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.331
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in ALP at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.353
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison ALP Highest Change Value During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.298
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    77. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in ALT, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    19.5
    20.0
    Change at Week 52 LOCF
    -1.0
    0.0
    Highest Value of Change in Phase 3
    6.0
    5.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline ALT
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.111
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change in ALT at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.948
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison ALT Highest Change Value During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.559
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    78. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in AST, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    20.0
    22.0
    Change at Week 52 LOCF
    1.0
    -1.0
    Highest Value of Change in Phase 3
    5.0
    6.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline AST
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.077
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change in AST at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.255
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison AST Highest Change Value During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.918
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    79. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in BUN, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 138 135
    Baseline
    11.0
    12.0
    Change at Week 52 LOCF
    0.0
    0.0
    Highest Value of Change in Phase 3
    3.0
    2.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline BUN
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.118
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in BUN at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.532
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison BUN Highest Value of Change During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.169
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    80. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Total Cholesterol (Fasting), Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 158 156
    Baseline
    180.0
    181.0
    Change at Week 52 LOCF
    5.0
    -0.5
    Highest Value of Change in Phase 3
    18.5
    20.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Total Cholesterol (fasting)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.878
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in Total Cholesterol (fasting) at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.544
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Total Cholesterol (fasting) in Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.658
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    81. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Creatine Kinase, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    82.0
    91.5
    Change at Week 52 LOCF
    5.0
    -2.0
    Highest Value of Change in Phase 3
    33.0
    28.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Creatine Kinase
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.043
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from baseline in Creatine Kinase at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.019
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Creatine Kinase During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.176
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    82. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Creatinine, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 161
    Baseline
    0.900
    0.900
    Change at Week 52 LOCF
    0.000
    0.000
    Highest Value of Change in Phase 3
    0.100
    0.100
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Creatinine
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.105
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in Creatinine at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.634
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Creatinine During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.958
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    83. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Eosinophils (Relative), Phase 3 Safety Sample
    Description The change values reported are the median of (post baseline percentage (of white blood cell count) minus baseline percentage (of white blood cell count).
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    2.30
    2.20
    Change at Week 52 LOCF
    0.00
    -0.10
    Highest Value of Change in Phase 3
    0.80
    0.90
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Eosinophils (relative)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.507
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in Eosinophils (relative) at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.834
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Eosinophils (relative) During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.511
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    84. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Glucose (Fasting), Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 157 155
    Baseline
    90.0
    90.0
    Change at Week 52 LOCF
    0.0
    0.0
    Highest Value of Change in Phase 3
    6.0
    7.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Glucose (fasting)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.741
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in Glucose (fasting) at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.962
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Change Value in Glucose (fasting) During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.592
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    85. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Lowest Value of Change in Hemoglobin, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    13.80
    14.00
    Change at Week 52 LOCF
    -0.10
    -0.10
    Lowest Value of Change in Phase 3
    -0.50
    -0.60
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Hemoglobin
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.080
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in Hemoglobin at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.868
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Lowest Change Value in Hemoglobin During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.299
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    86. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Lowest Value of Change in Hematocrit, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    41.40
    42.15
    Change at Week 52 LOCF
    -0.40
    -0.30
    Lowest Value of Change in Phase 3
    -1.60
    -1.90
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Hematocrit
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.187
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in Hematocrit During Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.377
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Lowest Value of Change in Hematocrit During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.494
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    87. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Lowest Value of Change in HDL Cholesterol (Fasting), Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 158 156
    Baseline
    46.0
    45.0
    Change at Week 52 LOCF
    -1.0
    -1.0
    Lowest Value of Change in Phase 3
    -5.0
    -5.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline HDL Cholesterol (fasting)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.180
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in HDL Cholesterol (fasting) at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.950
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Lowest Value of Change in HDL Cholesterol (fasting) During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.342
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    88. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-Percent Beta, Phase 3 Safety Sample
    Description HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 36 35
    Baseline
    120.0
    106.90
    Change at Week 52 LOCF
    -6.35
    8.50
    Highest Value of Change in Phase 3
    -10.85
    5.30
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline HOMA2-Percent Beta
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.349
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in HOMA2-Percent Beta at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.624
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value in HOMA2-Percent Beta During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.329
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    89. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-IR, Phase 3 Safety Sample
    Description HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 36 35
    Baseline
    1.24
    1.06
    Change from Baseline at Week 52 LOCF
    -0.13
    -0.13
    Highest Value of Change During Phase 3
    0.20
    0.37
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline HOMA2-IR
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.550
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline in HOMA2-IR at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.554
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in HOMA2-IR, Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.870
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    90. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Lactate Dehydrogenase, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 161
    Baseline
    161.0
    171.0
    Change at Week 52 LOCF
    4.0
    0.0
    Highest Value of Change During Phase 3
    25.0
    19.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Lactate Dehydrogenase
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Lactate Dehydrogenase
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.034
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Lactate Dehydrogenase During Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.091
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    91. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Change Value in LDL Cholesterol (Fasting), Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 158 156
    Baseline
    104.5
    100.0
    Change from Baseline in Week 52 LOCF
    3.5
    0.0
    Highest Value of Change During Phase 3
    16.0
    16.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline LDL Cholesterol (fasting)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.808
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.507
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Change Value in LDL Cholesterol (fasting)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.948
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    92. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Neutrophils (Relative), Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    61.55
    62.60
    Change from Week 52 LOCF
    -1.30
    -0.55
    Highest Value of Change During Phase 3
    -6.45
    -6.20
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Neutrophils (relative)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.967
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison in change from Baseline in Neutrophils (relative) at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.486
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Neutrophils (relative), Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.323
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    93. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Platelet Count, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest/lowest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 163 160
    Baseline
    252.0
    254.0
    Change from Baseline at Week 52 LOCF
    -1.0
    -3.5
    Highest Value of Change During Phase 3
    26.0
    17.5
    Lowest Value of Change During Phase 3
    -27.0
    -22.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline in Platelet Count
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.663
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.322
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Platelet Count, Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.358
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Lowest Value of Change in Platelet Count, Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.541
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    94. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Prolactin, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 154 147
    Baseline
    7.0
    6.0
    Change from Baseline in Week 52 LOCF
    2.0
    0.0
    Highest Value of Change During Phase 3
    3.0
    1.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Prolactin
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.412
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison, Change from Baseline at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Prolactin, Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    95. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Total Bilirubin, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 161
    Baseline
    0.40
    0.40
    Change from Baseline at Week 52 LOCF
    0.00
    0.00
    Highest Value of Change in Phase 3
    0.10
    0.10
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Total Bilirubin
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.630
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.675
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Total Bilirubin, Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.592
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    96. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Triglycerides (Fasting), Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 158 156
    Baseline
    130.0
    134.5
    Change from Baseline at Week 52 LOCF
    4.0
    0.0
    Highest Value of Change During Phase 3
    37.0
    42.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Triglycerides (fasting)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.273
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.489
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Triglycerides (fasting), Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.415
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    97. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Uric Acid, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    5.50
    5.75
    Change from Baseline at Week 52 LOCF
    -0.10
    0.00
    Highest Value of Change in Uric Acid
    0.65
    0.50
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Uric Acid
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.189
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.350
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Uric Acid, Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.799
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    98. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Leukocytes, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest/lowest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline
    6.900
    7.650
    Change from Baseline at Week 52 LOCF
    0.150
    -0.100
    Highest Value of Change During Phase 3
    1.100
    1.100
    Lowest Value of Change During Phase 3
    -0.900
    -1.000
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Leukocytes
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.124
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Change from Baseline at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.295
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value of Change in Leukocytes, Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.735
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Lowest Value of Change in Leukocytes, Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.505
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    99. Secondary Outcome
    Title Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
    Description Sinus Tachycardia: ≥120bpm+↑≥15bpm+no current diagnosis of supraventricular (SV) or ventricular tachycardia or atrial fibrillation (AF) or flutter or other rhythm abnormality (RA). Sinus Bradycardia:≥50bpm+↓≥15bpm+no current diagnosis of AF or flutter or other RA. AF:not present→present or present at rate <100bpm pretreatment to present with rate ≥100bpm+increase of ≥15bpm. AV=atrioventricular; PR=PR interval. Other Intraventricular Block: QRS wave ≥0.12 sec+↑≥0.02 sec+no current diagnosis of left or right bundle branch block. Old Infarction not present→present at ≥12 weeks post study entry.
    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])

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample
    Arm/Group Title Lithium Valproate
    Arm/Group Description Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg Depakote/valproic acid oral tablets
    Measure Participants 166 167
    Tachycardia ≥ 120 bpm and ↑ ≥ 15 bpm
    1
    0.6%
    0
    0%
    Bradycardia ≤ 50 bpm and ↓ 15 bpm
    1
    0.6%
    1
    0.6%
    Sinus Tachycardia (see description)
    1
    0.6%
    0
    0%
    Sinus Bradycardia (see description)
    1
    0.6%
    1
    0.6%
    SV Premature Beat - not present → present
    1
    0.6%
    1
    0.6%
    Ventricular Premature Beat - not present → present
    1
    0.6%
    0
    0%
    SV Tachycardia not present → present
    0
    0%
    0
    0%
    Ventricular Tachycardia not present → present
    0
    0%
    0
    0%
    Atrial Fibrillation (see description)
    0
    0%
    0
    0%
    Atrial Flutter not present → present
    0
    0%
    0
    0%
    1st Degree AV Block PR ≥0.20 sec and ↑ ≥0.05 sec
    0
    0%
    0
    0%
    2nd Degree AV Block not present → present
    0
    0%
    0
    0%
    3rd Degree AV Block not present → present
    0
    0%
    0
    0%
    Left Bundle Branch Block not present → present
    12
    7.1%
    9
    5.4%
    Right Bundle Branch Block not present → present
    6
    3.6%
    3
    1.8%
    Pre-excitation Syndrome not present → present
    0
    0%
    0
    0%
    Other Intraventricular Block (see description)
    1
    0.6%
    0
    0%
    Acute Infarction not present → present
    0
    0%
    0
    0%
    Subacute (Recent) Infarction not present → present
    1
    0.6%
    2
    1.2%
    Old Infarction (see description)
    0
    0%
    0
    0%
    Myocardial Ischemia not present → present
    1
    0.6%
    2
    1.2%
    Symmetrical T-Wave Inversion not present → present
    0
    0%
    1
    0.6%
    QTc Bazett (QTcB) > 450 msec
    12
    7.1%
    15
    8.9%
    QTc Frederica (QTcF) > 450 msec
    5
    3%
    4
    2.4%
    QTcB > 500 msec
    0
    0%
    1
    0.6%
    QTcF > 500 msec
    0
    0%
    1
    0.6%
    QTcB Change from Baseline > 30 msec
    20
    11.8%
    25
    14.9%
    QTcF Change from Baseline > 30 msec
    10
    5.9%
    20
    11.9%
    QTcB Change from Baseline > 60 msec
    3
    1.8%
    4
    2.4%
    QTcF Change from Baseline > 60 msec
    2
    1.2%
    3
    1.8%
    100. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in QT Interval Corrected for Heart Rate (QTc) Bazett, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 139 139
    Baseline
    415.0
    410.0
    Change from Baseline at Week 52 LOCF
    3.0
    3.0
    Highest Value of Change in QTc Bazett
    6.0
    12.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline QTc Bazett
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.213
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison, Change from Baseline in QTc Bazett at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.708
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in QTc Bazett, Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.107
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    101. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in QTc (0.33), Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 139 139
    Baseline
    404.0
    400.0
    Change from Baseline at Week 52 LOCF
    1.0
    2.0
    Highest Value of Change in QTc (0.33)
    3.0
    10.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline QTc (0.33)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.205
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison, Change from Baseline in QTc (0.33) at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.669
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in QTc (0.33), Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.072
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    102. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in PR, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 139 139
    Baseline
    155.0
    150.0
    Change from Baseline at Week 52 LOCF
    -2.0
    0.0
    Highest Value of Change in PR
    2.0
    4.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline PR
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison, Change from Baseline in PR at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in PR, Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.128
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    103. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in RR, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 139 139
    Baseline
    857.0
    870.0
    Change from Baseline at Week 52 LOCF
    3.0
    -4.0
    Highest Value of Change in RR
    38.0
    20.0
    Lowest Value of Change in RR
    -15.0
    -42.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline RR
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.571
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison, Change from Baseline in RR at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.353
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in RR, Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.204
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Lowest Value of Change in Prolactin, Phase 3 Safety Sample
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.435
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    104. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in QRS, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 139 139
    Baseline
    89.0
    90.0
    Change from Baseline at Week 52 LOCF
    0.0
    0.0
    Highest Value of Change in QRS
    2.0
    2.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline QRS
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.826
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison, Change from Baseline in QRS at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.545
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in QRS, Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.372
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    105. Secondary Outcome
    Title Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
    Description The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50(lower scores=less severe). Negative change scores indicate improvement.
    Time Frame Baseline, Weeks 4,8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline (n=164, 162)
    10.48
    (0.09)
    10.50
    (0.09)
    Change at Week 4 (n=160, 161)
    -0.02
    (0.07)
    0.04
    (0.07)
    Change at Week 8 (n=151, 145)
    -0.13
    (0.06)
    -0.03
    (0.06)
    Change at Week 12 (n=144, 136)
    -0.20
    (0.05)
    -0.10
    (0.05)
    Change at Week 24 (n=113, 120)
    -0.24
    (0.07)
    -0.02
    (0.06)
    Change at Week 36 (n=97, 104)
    -0.26
    (0.09)
    0.01
    (0.08)
    Change at Week 52 (n=85, 95)
    -0.24
    (0.08)
    -0.07
    (0.07)
    Change at Week 52 LOCF (n=164, 162)
    -0.20
    (0.06)
    -0.10
    (0.06)
    Highest Value in Change During Phase 3 (n=164,162)
    0.17
    (0.10)
    0.53
    (0.10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.235
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -0.07 to 0.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value in Change Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.36
    Confidence Interval (2-Sided) 95%
    0.08 to 0.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    106. Secondary Outcome
    Title Median Baseline, Change From Baseline, and Highest Value of Change in Heart Rate, Phase 3 Safety Sample
    Description
    Time Frame Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, participants with measurement
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 139 139
    Baseline
    70.0
    69.0
    Change from Baseline at Week 52 LOCF
    0.0
    0.0
    Highest Value of Change in Heart Rate
    1.0
    3.0
    Lowest Value of Change in Heart Rate
    -3.0
    -2.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Baseline Heart Rate
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.587
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison, Change from Baseline in Heart Rate at Week 52 (LOCF)
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.386
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Highest Value of Change in Heart Rate, Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.405
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Treatment Comparison Lowest Value of Change in Heart Rate, Phase 3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.253
    Comments Wilcoxon Rank Sum Test stratified by mood stabilizer
    Method Wilcoxon Rank Sum Test
    Comments
    107. Secondary Outcome
    Title Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
    Description The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
    Time Frame Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline (n=164, 162)
    0.11
    (0.05)
    0.14
    (0.05)
    Change at Week 4 (n=160, 162)
    -0.01
    (0.05)
    0.05
    (0.04)
    Change at Week 8 (n=151, 145)
    0.11
    (0.08)
    0.11
    (0.08)
    Change at Week 12 (n=144, 136)
    0.10
    (0.07)
    -0.01
    (0.07)
    Change at Week 24 (n=113, 120)
    0.13
    (0.09)
    -0.03
    (0.08)
    Change at Week 36 (n=97, 105)
    0.08
    (0.08)
    -0.07
    (0.08)
    Change at Week 52 (n=85, 96)
    0.06
    (0.08)
    -0.02
    (0.08)
    Change at Week 52 LOCF (n=164, 162)
    0.01
    (0.06)
    0.06
    (0.06)
    Highest Value in Change During Phase 3 (n=164,162)
    0.16
    (0.10)
    0.28
    (0.10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.514
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.06
    Confidence Interval (2-Sided) 95%
    -0.12 to 0.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value of Change Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.362
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.12
    Confidence Interval (2-Sided) 95%
    -0.14 to 0.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    108. Secondary Outcome
    Title Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
    Description The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 8 Score range from 0 to 4. A negative score signifies improvement.
    Time Frame Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline (n=164, 162)
    0.04
    (0.02)
    0.03
    (0.02)
    Change at Week 4 (n=160, 162)
    -0.01
    (0.01)
    0.03
    (0.01)
    Change at Week 8 (n=151, 145)
    0.01
    (0.02)
    0.02
    (0.02)
    Change at Week 12 (n=144, 136)
    0.02
    (0.02)
    0.01
    (0.02)
    Change at Week 24 (n=113, 120)
    0.02
    (0.02)
    0.00
    (0.02)
    Change at Week 36 (n=97, 105)
    0.01
    (0.02)
    -0.00
    (0.02)
    Change at Week 52 (n=85, 96)
    -0.00
    (0.02)
    -0.01
    (0.02)
    Change at Week 52 LOCF (n=164, 162)
    0.01
    (0.02)
    0.01
    (0.02)
    Highest Value in Change During Phase 3 (n=164,162)
    0.03
    (0.02)
    0.07
    (0.02)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.904
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.00
    Confidence Interval (2-Sided) 95%
    -0.04 to 0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value of Change Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.222
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.03 to 0.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    109. Secondary Outcome
    Title Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
    Description The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 9 Score range from 0 to 4. A negative score signifies improvement.
    Time Frame Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline (n=164, 162)
    0.01
    (0.01)
    0.01
    (0.01)
    Change at Week 4 (n=160, 162)
    -0.01
    (0.01)
    0.01
    (0.01)
    Change at Week 8 (n=151, 145)
    0.03
    (0.02)
    0.02
    (0.02)
    Change at Week 12 (n=144, 136)
    0.03
    (0.02)
    0.01
    (0.02)
    Change at Week 24 (n=113, 120)
    0.03
    (0.02)
    0.01
    (0.02)
    Change at Week 36 (n=97, 105)
    0.03
    (0.02)
    -0.00
    (0.02)
    Change at Week 52 (n=85, 96)
    0.02
    (0.02)
    -0.00
    (0.02)
    Change at Week 52 LOCF (n=164, 162)
    0.01
    (0.01)
    0.01
    (0.01)
    Highest Value in Change During Phase 3 (n=164,162)
    0.04
    (0.02)
    0.05
    (0.02)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.808
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.00
    Confidence Interval (2-Sided) 95%
    -0.03 to 0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value of Change Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.771
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    110. Secondary Outcome
    Title Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
    Description The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 10 Score range from 0 to 4. A negative score signifies improvement.
    Time Frame Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline (n=164, 162)
    0.02
    (0.01)
    0.04
    (0.01)
    Change at Week 4 (n=160, 162)
    -0.00
    (0.01)
    0.03
    (0.01)
    Change at Week 8 (n=151, 145)
    0.02
    (0.02)
    0.01
    (0.02)
    Change at Week 12 (n=144, 136)
    0.02
    (0.02)
    0.00
    (0.02)
    Change at Week 24 (n=113, 120)
    0.05
    (0.03)
    -0.01
    (0.02)
    Change at Week 36 (n=97, 105)
    0.02
    (0.02)
    -0.02
    (0.02)
    Change at Week 52 (n=85, 96)
    0.01
    (0.02)
    -0.03
    (0.02)
    Change at Week 52 LOCF (n=164, 162)
    0.00
    (0.01)
    -0.01
    (0.01)
    Highest Value in Change During Phase 3 (n=164,162)
    0.04
    (0.02)
    0.06
    (0.02)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.576
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.01
    Confidence Interval (2-Sided) 95%
    -0.05 to 0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.636
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.02
    Confidence Interval (2-Sided) 95%
    -0.05 to 0.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    111. Secondary Outcome
    Title Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
    Description The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
    Time Frame Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 164 162
    Baseline (n=164, 162)
    0.10
    (0.04)
    0.16
    (0.04)
    Change at Week 4 (n=160, 162)
    -0.01
    (0.03)
    0.01
    (0.03)
    Change at Week 8 (n=151, 144)
    -0.06
    (0.02)
    -0.04
    (0.02)
    Change at Week 12 (n=144, 136)
    -0.07
    (0.03)
    -0.03
    (0.03)
    Change at Week 24 (n=113, 120)
    -0.06
    (0.03)
    -0.04
    (0.03)
    Change at Week 36 (n=97, 104)
    -0.09
    (0.03)
    -0.05
    (0.03)
    Change at Week 52 (n=85, 96)
    -0.10
    (0.03)
    -0.07
    (0.03)
    Change at Week 52 LOCF (n=164, 162)
    -0.06
    (0.02)
    -0.05
    (0.02)
    Highest Value in Change During Phase 3 (n=164,162)
    0.07
    (0.04)
    0.11
    (0.04)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Week 52 LOCF Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.774
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.01
    Confidence Interval (2-Sided) 95%
    -0.06 to 0.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Aripiprazole
    Comments Highest Value of Change, Treatment Difference
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.444
    Comments ANOVA model, controlling for treatment and mood stabilizer, is used for baseline. ANCOVA model, controlling for treatment, mood stabilizer, and baseline value, is used for mean change from baseline.
    Method ANOVA/ANCOVA
    Comments Means, differences in means, 95% CI for the differences and p-values are based on the ANOVA/ANCOVA model.
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.06 to 0.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    112. Secondary Outcome
    Title Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3
    Description
    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])

    Outcome Measure Data

    Analysis Population Description
    Phase 3 Safety Sample
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 166 167
    Any EPS Medications
    36
    21.3%
    40
    23.8%
    Cardiovascular System-Propanolol
    18
    10.7%
    21
    12.5%
    Nervous System-Benztropine
    10
    5.9%
    19
    11.3%
    Nervous System-Biperiden
    4
    2.4%
    2
    1.2%
    Nervous System-Trihexyphenidyl
    11
    6.5%
    10
    6%
    113. Secondary Outcome
    Title Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
    Description 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 normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed=extension phase participants, observed cases (OC) data set; n=number of participants evaluated at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Mean Baseline (N=19, 23)
    1.26
    (0.104)
    1.35
    (0.102)
    Mean Change at Week 8 (n=19, 23)
    -0.26
    (0.104)
    -0.30
    (0.098)
    Mean Change at Week 16 (n=18, 23)
    -0.28
    (0.109)
    -0.30
    (0.098)
    Mean Change at Week 24 (n=17, 20)
    -0.29
    (0.114)
    -0.40
    (0.112)
    Mean Change at Week 32 (n=15, 15)
    0.00
    (0.309)
    -0.33
    (0.126)
    Mean Change at Week 40 (n=9, 12)
    -0.11
    (0.111)
    -0.33
    (0.142)
    Mean Change at Week 48 (n=9, 9)
    -0.11
    (0.111)
    -0.22
    (0.147)
    Mean Change at Week 56 (n=5, 9)
    0.00
    (0.000)
    -0.22
    (0.147)
    Mean Change at Week 64 (n=5, 4)
    0.00
    (0.000)
    0.00
    (0.000)
    Mean Change at Week 72 (n=1, 2)
    0.00
    (0.000)
    -0.50
    (0.500)
    114. Secondary Outcome
    Title Extension Phase: Mean Change From Baseline in CGI-BP (Mania) Severity of Illness at Extension Phase Endpoint
    Description 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 normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    extension phase participants, last observation carried forward (LOCF)
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Mean (Standard Error) [units on a scale]
    -0.05
    (0.247)
    -0.35
    (0.102)
    115. Secondary Outcome
    Title Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Depression) at Extension Phase Endpoint
    Description 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 normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    extension phase participants, last observation carried forward (LOCF)
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Mean (Standard Error) [units on a scale]
    -0.16
    (0.138)
    0.00
    (0.000)
    116. Secondary Outcome
    Title Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
    Description 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 normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed=extension phase participants, observed cases (OC) data set; n=number of participants evaluated at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Mean Baseline (N=19, 23)
    1.21
    (0.123)
    1.00
    (0.000)
    Mean Change at Week 8 (n=19, 23)
    -0.11
    (0.130)
    0.00
    (0.000)
    Mean Change at Week 16 (n=18, 23)
    -0.11
    (0.137)
    0.00
    (0.000)
    Mean Change at Week 24 (n=17, 20)
    -0.12
    (0.146)
    0.00
    (0.000)
    Mean Change at Week 32 (n=15, 15)
    -0.20
    (0.175)
    0.00
    (0.000)
    Mean Change at Week 40 (n=9, 12)
    -0.11
    (0.200)
    0.00
    (0.000)
    Mean Change at Week 48 (n=9, 9)
    -0.11
    (0.200)
    0.00
    (0.000)
    Mean Change at Week 56 (n=5, 9)
    -0.20
    (0.200)
    0.00
    (0.000)
    Mean Change at Week 64 (n=5, 4)
    -0.20
    (0.200)
    0.00
    (0.000)
    Mean Change at Week 72 (n=1, 2)
    0.00
    (0.00)
    0.00
    (0.000)
    117. Secondary Outcome
    Title Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
    Description 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 normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed=extension phase participants, observed cases (OC) data set; n=number of participants evaluated at time point
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Mean Baseline (N=19, 23)
    1.37
    (0.114)
    1.35
    (0.102)
    Mean Change at Week 8 (n=19, 23)
    -0.26
    (0.129)
    -0.30
    (0.098)
    Mean Change at Week 16 (n=18, 23)
    -0.28
    (0.135)
    -0.30
    (0.098)
    Mean Change at Week 24 (n=17, 20)
    -0.29
    (0.143)
    -0.40
    (0.112)
    Mean Change at Week 32 (n=15, 15)
    -0.07
    (0.330)
    -0.33
    (0.126)
    Mean Change at Week 40 (n=9, 12)
    -0.22
    (0.222)
    -0.33
    (0.142)
    Mean Change at Week 48 (n=9, 9)
    -0.22
    (0.222)
    -0.22
    (0.147)
    Mean Change at Week 56 (n=5, 9)
    -0.20
    (0.200)
    -0.22
    (0.147)
    Mean Change at Week 64 (n=5, 4)
    -0.20
    (0.200)
    0.00
    (0.000)
    Mean Change at Week 72 (n=1, 2)
    0.00
    (0.00)
    -0.50
    (0.500)
    118. Secondary Outcome
    Title Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Overall) at Extension Phase Endpoint
    Description 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 normal and 7 being very severely ill). A negative change score signifies improvement.
    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])

    Outcome Measure Data

    Analysis Population Description
    extension phase participants, last observation carried forward (LOCF)
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Mean (Standard Error) [units on a scale]
    -0.11
    (0.264)
    -0.35
    (0.102)
    119. Secondary Outcome
    Title Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations
    Description Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
    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])

    Outcome Measure Data

    Analysis Population Description
    Extension Phase Safety Sample
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Deaths
    0
    0%
    0
    0%
    SAEs
    0
    0%
    0
    0%
    AEs
    5
    3%
    8
    4.8%
    Discontinuations due to AEs
    1
    0.6%
    0
    0%
    Treatment-related AEs
    2
    1.2%
    1
    0.6%
    120. Secondary Outcome
    Title Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
    Description Metabolic abnormalities considered by the investigator as clinically relevant. (Need normal values for each.)
    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])

    Outcome Measure Data

    Analysis Population Description
    Number of Participants Analyzed=Participants in Extension Phase Safety Sample; n=number of participants with evaluation
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Glucose, non-fasting (n=3,1)
    0
    0%
    0
    0%
    Glucose, fasting (n=17, 22)
    2
    1.2%
    3
    1.8%
    HDL Cholesterol, combined (n=18, 22)
    12
    7.1%
    11
    6.5%
    HDL Cholesterol, fasting (n=17, 22)
    12
    7.1%
    11
    6.5%
    HDL Cholesterol, non-fasting (n=2, 1)
    0
    0%
    0
    0%
    Total Cholesterol, combined (n=18, 22)
    0
    0%
    1
    0.6%
    Total Cholesterol, fasting (n=17, 22)
    0
    0%
    1
    0.6%
    Total Cholesterol, non-fasting (n=2, 1)
    0
    0%
    0
    0%
    LDL Cholesterol, combined (n=18, 22)
    1
    0.6%
    3
    1.8%
    LDL Cholesterol, fasting (n=17, 22)
    1
    0.6%
    3
    1.8%
    LDL Cholesterol, non-fasting (n=2, 1)
    0
    0%
    0
    0%
    Triglycerides, combined (n=18, 22)
    4
    2.4%
    0
    0%
    Triglycerides, fasting (n=17, 22)
    4
    2.4%
    0
    0%
    Triglycerides, non-fasting (n=2, 1)
    0
    0%
    0
    0%
    121. Secondary Outcome
    Title Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
    Description Vital sign abnormalities considered by the investigator as clinically relevant.
    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])

    Outcome Measure Data

    Analysis Population Description
    Extension Phase Safety Sample
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Systolic Blood Pressure Increase
    0
    0%
    0
    0%
    Systolic Blood Pressure Decrease
    0
    0%
    0
    0%
    Diastolic Blood Pressure Increase
    0
    0%
    0
    0%
    Diastolic Blood Pressure Decrease
    0
    0%
    0
    0%
    Heart Rate Increase
    0
    0%
    0
    0%
    Heart Rate Decrease
    0
    0%
    0
    0%
    Weight Increase
    1
    0.6%
    7
    4.2%
    Weight Decrease
    2
    1.2%
    1
    0.6%
    122. Secondary Outcome
    Title Extension Phase: Adverse Events (AEs), by Maximum Intensity
    Description AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
    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])

    Outcome Measure Data

    Analysis Population Description
    Participants in Extension Phase Safety Sample with AEs
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 19 23
    Mild / Grade 1
    4
    2.4%
    7
    4.2%
    Moderate / Grade 2
    1
    0.6%
    2
    1.2%
    Severe / Grade 3
    0
    0%
    0
    0%
    Very Severe / Grade 4
    0
    0%
    0
    0%
    123. Secondary Outcome
    Title Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities
    Description Chemistry, hematology, and urinalysis abnormalities considered by the investigator as clinically relevant. Hematocrit: ≤37%(M)/≤32%(F)+3 percentage pts↓from baseline.
    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])

    Outcome Measure Data

    Analysis Population Description
    Participants in Extension Phase Safety Sample with laboratory evaluation
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 18 22
    Creatine Kinase >= 3 x ULN
    1
    0.6%
    0
    0%
    Hematocrit (see description)
    2
    1.2%
    0
    0%
    Hemoglobin ≤11.5 g/dL(M)/≤9.5 g/dL(F)
    2
    1.2%
    0
    0%
    Eosinophils relative (calculated) ≥10%
    2
    1.2%
    2
    1.2%
    Urine Glucose (any glucose in the urine)
    0
    0%
    2
    1.2%
    124. Secondary Outcome
    Title Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
    Description ECG abnormalities considered by the investigator as clinically relevant.Left Bundle Branch Block: Not present at Baseline--> present post-baseline.
    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])

    Outcome Measure Data

    Analysis Population Description
    Participants in Extension Phase Safety Sample with ECG evaluation
    Arm/Group Title Placebo Aripiprazole
    Arm/Group Description 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 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
    Measure Participants 17 21
    Left Bundle Branch Block (see description)
    4
    2.4%
    1
    0.6%
    QTcB > 450 msec
    1
    0.6%
    3
    1.8%
    QTcF > 450 msec
    1
    0.6%
    1
    0.6%
    QTcB Change from Baseline > 30 msec
    3
    1.8%
    5
    3%
    QTcF Change from Baseline > 30 msec
    4
    2.4%
    3
    1.8%
    QTcB Change from Baseline > 60 msec
    1
    0.6%
    0
    0%
    QTcF Change from Baseline > 60 msec
    1
    0.6%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Single-Blind Aripiprazole Double-Blind Placebo Double-Blind Aripiprazole Extension Phase Placebo Extension Phase Aripiprazole
    Arm/Group Description 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. 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. 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. Phase 4 (Extension Phase): matching placebo oral tablets and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml. Phase 4 (Extension 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.
    All Cause Mortality
    Single-Blind Aripiprazole Double-Blind Placebo Double-Blind Aripiprazole Extension Phase Placebo Extension Phase Aripiprazole
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Single-Blind Aripiprazole Double-Blind Placebo Double-Blind Aripiprazole Extension Phase Placebo Extension Phase Aripiprazole
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/682 (2.2%) 8/166 (4.8%) 11/167 (6.6%) 0/19 (0%) 0/23 (0%)
    General disorders
    CHEST PAIN 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    DECAPITATION 0/682 (0%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    NON-CARDIAC CHEST PAIN 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    Infections and infestations
    PNEUMONIA 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    CELLULITIS 0/682 (0%) 2/166 (1.2%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    APPENDICITIS 0/682 (0%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    GASTRITIS VIRAL 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    Injury, poisoning and procedural complications
    ACCIDENTAL OVERDOSE 2/682 (0.3%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BREAST CANCER 0/682 (0%) 1/166 (0.6%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    UTERINE LEIOMYOMA 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    Nervous system disorders
    RADIAL NERVE PALSY 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    Psychiatric disorders
    MANIA 0/682 (0%) 2/166 (1.2%) 2/167 (1.2%) 0/19 (0%) 0/23 (0%)
    AGITATION 0/682 (0%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    AGGRESSION 0/682 (0%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    DEPRESSION 3/682 (0.4%) 2/166 (1.2%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    ALCOHOL ABUSE 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    SUICIDE ATTEMPT 1/682 (0.1%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    BIPOLAR DISORDER 0/682 (0%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    MAJOR DEPRESSION 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    SUICIDAL IDEATION 0/682 (0%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    BIPOLAR I DISORDER 0/682 (0%) 1/166 (0.6%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    PSYCHOTIC DISORDER 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    HALLUCINATION, VISUAL 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    HALLUCINATION, AUDITORY 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 0/19 (0%) 0/23 (0%)
    Renal and urinary disorders
    RENAL FAILURE ACUTE 0/682 (0%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    Reproductive system and breast disorders
    BARTHOLIN'S CYST 0/682 (0%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    Other (Not Including Serious) Adverse Events
    Single-Blind Aripiprazole Double-Blind Placebo Double-Blind Aripiprazole Extension Phase Placebo Extension Phase Aripiprazole
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 402/682 (58.9%) 61/166 (36.7%) 68/167 (40.7%) 5/19 (26.3%) 6/23 (26.1%)
    Gastrointestinal disorders
    NAUSEA 60/682 (8.8%) 4/166 (2.4%) 5/167 (3%) 0/19 (0%) 0/23 (0%)
    DIARRHOEA 39/682 (5.7%) 6/166 (3.6%) 7/167 (4.2%) 1/19 (5.3%) 0/23 (0%)
    GASTRITIS 1/682 (0.1%) 3/166 (1.8%) 1/167 (0.6%) 2/19 (10.5%) 0/23 (0%)
    ANAL FISSURE 0/682 (0%) 0/166 (0%) 0/167 (0%) 1/19 (5.3%) 0/23 (0%)
    HAEMORRHOIDS 1/682 (0.1%) 0/166 (0%) 0/167 (0%) 1/19 (5.3%) 0/23 (0%)
    General disorders
    PYREXIA 13/682 (1.9%) 5/166 (3%) 7/167 (4.2%) 1/19 (5.3%) 1/23 (4.3%)
    Investigations
    WEIGHT INCREASED 28/682 (4.1%) 11/166 (6.6%) 15/167 (9%) 0/19 (0%) 1/23 (4.3%)
    Musculoskeletal and connective tissue disorders
    PAIN IN EXTREMITY 5/682 (0.7%) 3/166 (1.8%) 2/167 (1.2%) 1/19 (5.3%) 0/23 (0%)
    Nervous system disorders
    TREMOR 94/682 (13.8%) 4/166 (2.4%) 10/167 (6%) 0/19 (0%) 1/23 (4.3%)
    HEADACHE 61/682 (8.9%) 18/166 (10.8%) 22/167 (13.2%) 1/19 (5.3%) 1/23 (4.3%)
    SEDATION 40/682 (5.9%) 0/166 (0%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    AKATHISIA 99/682 (14.5%) 3/166 (1.8%) 6/167 (3.6%) 0/19 (0%) 0/23 (0%)
    DIZZINESS 43/682 (6.3%) 3/166 (1.8%) 7/167 (4.2%) 0/19 (0%) 0/23 (0%)
    SOMNOLENCE 53/682 (7.8%) 3/166 (1.8%) 1/167 (0.6%) 0/19 (0%) 0/23 (0%)
    EXTRAPYRAMIDAL DISORDER 37/682 (5.4%) 1/166 (0.6%) 5/167 (3%) 0/19 (0%) 0/23 (0%)
    Psychiatric disorders
    INSOMNIA 61/682 (8.9%) 16/166 (9.6%) 9/167 (5.4%) 0/19 (0%) 2/23 (8.7%)
    MOOD ALTERED 1/682 (0.1%) 1/166 (0.6%) 0/167 (0%) 1/19 (5.3%) 0/23 (0%)
    RESTLESSNESS 36/682 (5.3%) 0/166 (0%) 2/167 (1.2%) 0/19 (0%) 0/23 (0%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 4/682 (0.6%) 1/166 (0.6%) 3/167 (1.8%) 1/19 (5.3%) 0/23 (0%)
    Skin and subcutaneous tissue disorders
    DERMATITIS 1/682 (0.1%) 1/166 (0.6%) 0/167 (0%) 1/19 (5.3%) 0/23 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/Title BMS Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00261443
    Other Study ID Numbers:
    • CN138-189
    First Posted:
    Dec 5, 2005
    Last Update Posted:
    Dec 2, 2013
    Last Verified:
    Apr 1, 2011