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Phase 4 N=1,270 Randomized Double-blind Treatment

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

Bipolar Disorder

Enrolled (actual)
1,270
Serious AEs
3.2%
Results posted
Apr 2011
Primary outcome: Primary: Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3 — 1.00; 1.00; 0.95; 0.96 proportion of participants — p=0.014

Study Design & Population

Study type
Interventional
Phase
Phase 4
Interventions
Lithium or Valproate with placebo (PBO) (Drug); Lithium or Valproate with Aripiprazole (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Primary completion
Jun 2009

Outcome Measures

OutcomeResultp-value
PRIMARY
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
1.00; 1.00; 0.95; 0.96; 0.93; 0.94 0.014 sig
SECONDARY
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
1.54; 1.54; 0.01; 0.05; 0.05; 0.01 0.911
SECONDARY
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
1.00; 1.00; 0.99; 0.99; 0.99; 0.98 0.013 sig
SECONDARY
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
1.00; 1.00; 0.96; 0.98; 0.94; 0.97 0.384
SECONDARY
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
23.15; 22.32; -4.50; -4.86; -7.90; -7.82
SECONDARY
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
4.03; 4.06; 0.47; 0.53; 0.91; 0.23 0.955
SECONDARY
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
10.97; 11.56; -1.48; -1.51; -2.23; -2.70
SECONDARY
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
4.41; 4.62; 1.92; 1.42; 2.27; 1.23 0.590
SECONDARY
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
4.25; 4.08; -0.52; -0.53; -1.05; -0.97
SECONDARY
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
1.65; 1.70; 0.25; 0.27; 0.32; 0.21 0.597
SECONDARY
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
2.16; 2.33; -0.16; -0.19; -0.22; -0.33
SECONDARY
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
1.43; 1.47; 0.30; 0.29; 0.35; 0.24 0.588
SECONDARY
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
3.15; 3.09; 2.61; 2.58; 2.14; 2.24
SECONDARY
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
4.22; 4.06; -0.58; -0.58; -1.15; -1.06
SECONDARY
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
2.96; 3.00; 3.17; 2.98; 3.14; 3.03 0.774
SECONDARY
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
3.56; 3.40; 3.42; 3.25; 3.35; 3.19
SECONDARY
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
3.46; 3.56; 3.55; 3.52; 3.51; 3.45 0.486
SECONDARY
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
3.20; 3.13; 2.70; 2.69; 2.27; 2.40
SECONDARY
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
3.17; 3.27; 3.36; 3.22; 3.34; 3.27 0.488
SECONDARY
Number of Participants Maintaining Remission During Phase 3
142; 142; 138; 136; 133; 126 0.910
SECONDARY
Proportion of Participants Discontinuing For Any Reason Through Week 52 (During Phase 3)
0.473; 0.387 0.132
SECONDARY
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
0; 0; 5; 10; 38; 50
SECONDARY
Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
226; 287; 172; 219; 109; 165
SECONDARY
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
0; 2; 0; 4; 0; 2
SECONDARY
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
2; 4; 0; 4; 1; 6
SECONDARY
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
0; 0; 3; 6; 0; 3
SECONDARY
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
415.0; 412.0; 4.0; -8.0; 403.0; 400.0
SECONDARY
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
76.0; 74.0; 0.0; 0.0; 78.0; 82.0
SECONDARY
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
120.0; 120.0; 0.0; 0.0; 76.0; 77.5
SECONDARY
Median Baseline and Change From Baseline in Weight Vital Sign Measurements At Phase 2 Endpoint
76.2; 76.4; 0.9; 1.5
SECONDARY
Median Baseline and Change From Baseline in Body Mass Index (BMI) Vital Sign Measurements at Phase 2 Endpoint
26.9; 27.2; 0.3; 0.5
SECONDARY
Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
72.0; 64.0; 20.0; 17.0; 19.0; 20.0
SECONDARY
Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2
-2.0; -2.0; 0.0; 2.0; 0.0; 1.0
SECONDARY
Median Baseline and Change From Baseline in Heart Rate Measurements During Phase 2
71.0; 69.0; 0.0; 0
SECONDARY
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
11.0; 13.0; 182.0; 174.0; 0.900; 0.900
SECONDARY
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
0.0; 0.0; -1.0; 4.5; 0.0; 0.0
SECONDARY
Median Baseline Eosinophils (Relative) and Neutrophils (Relative)
2.50; 2.20; 67.60; 58.10
SECONDARY
Median Change From Baseline in Eosinophils (Relative) and Neutrophils (Relative)
-0.40; -0.20; 0.25; 0.60
SECONDARY
Median Baseline Hemoglobin
13.75; 13.80
SECONDARY
Median Change From Baseline in Hemoglobin
0.05; 0.10
SECONDARY
Median Baseline Hematocrit
41.30; 41.10
SECONDARY
Median Change From Baseline in Hematocrit
0.30; 0.20
SECONDARY
Median Baseline Homeostasis Model Assessment 2 (HOMA2)-Percent Beta
99.95; 118.70
SECONDARY
Median Baseline Homeostasis Model Assessment 2 HOMA2-Insulin Resistance (IR)
1.14; 1.42
SECONDARY
Median Change From Baseline in Homeostasis Model Assessment 2(HOMA2)-Percent Beta at Phase 2 Endpoint
7.70; 17.05
SECONDARY
Median Change From Baseline in HOMA2 Model Assesses Insulin Resistance (HOMA2-IR) at Phase 2 Endpoint
0.09; 0.15
SECONDARY
Median Baseline Platelet Count
297.0; 226.0
SECONDARY
Median Change From Baseline in Platelet Count at Phase 2 Endpoint
-4.0; -2.0
SECONDARY
Median Baseline Prolactin
10.0; 9.5
SECONDARY
Median Change From Baseline in Prolactin at Phase 2 Endpoint
-2.5; -3.0
SECONDARY
Median Baseline Leukocytes
8.350; 6.800
SECONDARY
Median Change From Baseline in Leukocytes at Phase 2 Endpoint
-0.100; -0.200
SECONDARY
Baseline Abnormal Involuntary Movement Scale (AIMS)
0.10; 0.08
SECONDARY
Unadjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) at Phase 2 Endpoint
0.05; 0.04
SECONDARY
Baseline in Simpson-Angus Scale (SAS) Total Score
10.28; 10.30
SECONDARY
Unadjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score at Phase 2 Endpoint
0.44; 0.15
SECONDARY
Baseline in Barnes Akathisia Global Clinical Assessment
0.09; 0.14
SECONDARY
Unadjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Phase 2 Endpoint
0.14; 0.07
SECONDARY
Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3
1; 1; 8; 11; 105; 105
SECONDARY
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
81; 84; 24; 21; 45; 47
SECONDARY
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
0; 0; 2; 1; 0; 0
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Systolic BP During Phase 3
120.0; 120.0; 0.0; 0.0; 8.0; 6.0 0.640
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Diastolic BP During Phase 3
78.0; 79.0; 0.0; 0.0; 5.5; 6.0 0.656
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Heart Rate During Phase 3
74.0; 74.0; 0.0; 1.0; 7.5; 8.0 0.619
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Systolic BP During Phase 3
120.0; 120.0; 2.0; 0.0; 8.0; 4.0 0.184
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Diastolic BP During Phase 3
80.0; 80.0; 0.0; -2.0; 4.0; 0.0 0.142
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Heart Rate During Phase 3
78.0; 76.0; -4.0; -2.0; 3.0; 4.0 0.916
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Systolic BP During Phase 3
120.0; 120.0; 0.0; 0.0; 8.0; 6.0 0.871
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Diastolic BP During Phase 3
78.0; 78.0; 0.0; 0.0; 6.0; 6.0 0.935
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Heart Rate During Phase 3
78.0; 78.0; 0.0; 1.0; 6.0; 7.0 0.850
SECONDARY
Baseline and Adjusted Mean Change From Baseline in Weight
81.33; 80.22; -1.00; 0.28; 0.35; 0.13 0.491
SECONDARY
Number of Participants Showing Relevant Weight Gain During Phase 3
3; 6; 6; 11; 16; 12 0.279
SECONDARY
Number of Participants Showing Relevant Weight Loss During Phase 3
5; 6; 7; 8; 7; 8 0.685
SECONDARY
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
27.0; 27.9; 0.0; 0.2; 0.1; 0.2 0.646
SECONDARY
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
2; 0; 3; 3; 0; 0
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Alkaline Phosphatase (ALP), Phase 3 Safety Sample
60.5; 62.5; 1.0; 0.0; 8.0; 7.0 0.331
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in ALT, Phase 3 Safety Sample
19.5; 20.0; -1.0; 0.0; 6.0; 5.0 0.111
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in AST, Phase 3 Safety Sample
20.0; 22.0; 1.0; -1.0; 5.0; 6.0 0.077
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in BUN, Phase 3 Safety Sample
11.0; 12.0; 0.0; 0.0; 3.0; 2.0 0.118
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Total Cholesterol (Fasting), Phase 3 Safety Sample
180.0; 181.0; 5.0; -0.5; 18.5; 20.5 0.878
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Creatine Kinase, Phase 3 Safety Sample
82.0; 91.5; 5.0; -2.0; 33.0; 28.0 0.043 sig
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Creatinine, Phase 3 Safety Sample
0.900; 0.900; 0.000; 0.000; 0.100; 0.100 0.105
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Eosinophils (Relative), Phase 3 Safety Sample
2.30; 2.20; 0.00; -0.10; 0.80; 0.90 0.507
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Glucose (Fasting), Phase 3 Safety Sample
90.0; 90.0; 0.0; 0.0; 6.0; 7.0 0.741
SECONDARY
Median Baseline, Change From Baseline, and Lowest Value of Change in Hemoglobin, Phase 3 Safety Sample
13.80; 14.00; -0.10; -0.10; -0.50; -0.60 0.080
SECONDARY
Median Baseline, Change From Baseline, and Lowest Value of Change in Hematocrit, Phase 3 Safety Sample
41.40; 42.15; -0.40; -0.30; -1.60; -1.90 0.187
SECONDARY
Median Baseline, Change From Baseline, and Lowest Value of Change in HDL Cholesterol (Fasting), Phase 3 Safety Sample
46.0; 45.0; -1.0; -1.0; -5.0; -5.0 0.180
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-Percent Beta, Phase 3 Safety Sample
120.0; 106.90; -6.35; 8.50; -10.85; 5.30 0.349
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-IR, Phase 3 Safety Sample
1.24; 1.06; -0.13; -0.13; 0.20; 0.37 0.550
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Lactate Dehydrogenase, Phase 3 Safety Sample
161.0; 171.0; 4.0; 0.0; 25.0; 19.0 0.004 sig
SECONDARY
Median Baseline, Change From Baseline, and Highest Change Value in LDL Cholesterol (Fasting), Phase 3 Safety Sample
104.5; 100.0; 3.5; 0.0; 16.0; 16.5 0.808
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Neutrophils (Relative), Phase 3 Safety Sample
61.55; 62.60; -1.30; -0.55; -6.45; -6.20 0.967
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Platelet Count, Phase 3 Safety Sample
252.0; 254.0; -1.0; -3.5; 26.0; 17.5 0.663
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Prolactin, Phase 3 Safety Sample
7.0; 6.0; 2.0; 0.0; 3.0; 1.0 0.412
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Total Bilirubin, Phase 3 Safety Sample
0.40; 0.40; 0.00; 0.00; 0.10; 0.10 0.630
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Triglycerides (Fasting), Phase 3 Safety Sample
130.0; 134.5; 4.0; 0.0; 37.0; 42.0 0.273
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Uric Acid, Phase 3 Safety Sample
5.50; 5.75; -0.10; 0.00; 0.65; 0.50 0.189
SECONDARY
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Leukocytes, Phase 3 Safety Sample
6.900; 7.650; 0.150; -0.100; 1.100; 1.100 0.124
SECONDARY
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
1; 0; 1; 1; 1; 0
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in QT Interval Corrected for Heart Rate (QTc) Bazett, Phase 3 Safety Sample
415.0; 410.0; 3.0; 3.0; 6.0; 12.0 0.213
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in QTc (0.33), Phase 3 Safety Sample
404.0; 400.0; 1.0; 2.0; 3.0; 10.0 0.205
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in PR, Phase 3 Safety Sample
155.0; 150.0; -2.0; 0.0; 2.0; 4.0 0.012 sig
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in RR, Phase 3 Safety Sample
857.0; 870.0; 3.0; -4.0; 38.0; 20.0 0.571
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in QRS, Phase 3 Safety Sample
89.0; 90.0; 0.0; 0.0; 2.0; 2.0 0.826
SECONDARY
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
10.48; 10.50; -0.02; 0.04; -0.13; -0.03 0.235
SECONDARY
Median Baseline, Change From Baseline, and Highest Value of Change in Heart Rate, Phase 3 Safety Sample
70.0; 69.0; 0.0; 0.0; 1.0; 3.0 0.587
SECONDARY
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
0.11; 0.14; -0.01; 0.05; 0.11; 0.11 0.514
SECONDARY
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
0.04; 0.03; -0.01; 0.03; 0.01; 0.02 0.904
SECONDARY
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
0.01; 0.01; -0.01; 0.01; 0.03; 0.02 0.808
SECONDARY
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
0.02; 0.04; -0.00; 0.03; 0.02; 0.01 0.576
SECONDARY
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
0.10; 0.16; -0.01; 0.01; -0.06; -0.04 0.774
SECONDARY
Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3
36; 40; 18; 21; 10; 19
SECONDARY
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
1.26; 1.35; -0.26; -0.30; -0.28; -0.30
SECONDARY
Extension Phase: Mean Change From Baseline in CGI-BP (Mania) Severity of Illness at Extension Phase Endpoint
-0.05; -0.35
SECONDARY
Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Depression) at Extension Phase Endpoint
-0.16; 0.00
SECONDARY
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
1.21; 1.00; -0.11; 0.00; -0.11; 0.00
SECONDARY
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
1.37; 1.35; -0.26; -0.30; -0.28; -0.30
SECONDARY
Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Overall) at Extension Phase Endpoint
-0.11; -0.35
SECONDARY
Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations
0; 0; 0; 0; 5; 8
SECONDARY
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
0; 0; 2; 3; 12; 11
SECONDARY
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
0; 0; 0; 0; 0; 0
SECONDARY
Extension Phase: Adverse Events (AEs), by Maximum Intensity
4; 7; 1; 2; 0; 0
SECONDARY
Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities
1; 0; 2; 0; 2; 0
SECONDARY
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
4; 1; 1; 3; 1; 1

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.

Eligibility Criteria

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00261443). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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