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

简要总结

主要结局

次要结局

• 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))
• 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]))
• 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))
• 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))
• 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]))
• 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)
• 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]))
• 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))
• 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]))
• 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))
• 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))
• 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]))
• 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]))
• 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))
• 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))
• Median Baseline Leukocytes(Baseline)
• 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)
• 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)
• 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))
• 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))
• 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]))
• 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))
• 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))
• 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]))
• 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))
• Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample(Baseline)
• 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]))
• 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))
• 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))
• 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))
• 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))
• 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)
• 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))
• 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))
• Median Baseline Homeostasis Model Assessment 2 (HOMA2)-Percent Beta(Baseline)
• 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))
• 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))
• 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))
• 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))
• Median Baseline Eosinophils (Relative) and Neutrophils (Relative)(Baseline)
• Median Baseline Hematocrit(Baseline)
• Median Baseline Homeostasis Model Assessment 2 HOMA2-Insulin Resistance (IR)(Baseline)
• 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))
• 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))
• 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)
• 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)
• 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))
• 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))
• Median Baseline Platelet Count(Baseline)
• Baseline in Simpson-Angus Scale (SAS) Total Score(Baseline)
• 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]))
• 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)
• 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)
• 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)
• 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))
• Median Baseline Hemoglobin(Baseline)
• 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))
• Median Baseline Prolactin(Baseline)
• Baseline Abnormal Involuntary Movement Scale (AIMS)(Baseline)
• 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)
• 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)
• 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)
• 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]))
• 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))
• 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))
• 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))
• 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))
• 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))
• Baseline in Barnes Akathisia Global Clinical Assessment(Baseline)
• 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]))
• 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)
• Baseline and Adjusted Mean Change From Baseline in Weight(Baseline, Weeks 12, 24, 36, 52, During Phase 3 (for highest value))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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]))
• 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)
• 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))
• 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)
• 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))
• 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))
• 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))
• 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))
• 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)
• 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))
• 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))
• 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))
• 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]))
• 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))
• 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]))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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))
• 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]))
• 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]))
• 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))
• 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))
• 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]))
• 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))
• 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]))
• 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]))
• 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]))
• 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]))
• 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]))
• 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]))
• 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]))
• 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]))
• 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]))