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

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

Source: ClinicalTrials.gov NCT00261443 ↗
Enrolled (actual)
1,270
Serious AEs
3.2%
Results posted
Apr 2011
Primary outcomePrimary: 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

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.

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

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. Informational only — not medical advice.

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