Phase 3
N=514
Olanzapine Treatment of Patients With Bipolar I Disorder
Depression, Bipolar
Bottom Line
View on ClinicalTrials.gov: NCT00510146 ↗Enrolled (actual)
514
Serious AEs
3.0%
Results posted
May 2011
Primary outcome: Primary: Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase) — 29.36; 28.69; -14.26; -11.71 units on a scale — p=0.018
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Olanzapine (Drug); Placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Eli Lilly and Company
- Primary completion
- Mar 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase) |
29.36; 28.69; -14.26; -11.71 | 0.018 sig |
| SECONDARY Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase) |
52.5; 43.3 | 0.050 |
| SECONDARY Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase) |
53.9; 49.7 | 0.367 |
| SECONDARY Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) |
1.07; 1.11; 0.00; 0.09; 4.54; 4.53 | 0.008 sig |
| SECONDARY Percentage of Participants With Recovery (Acute Phase) |
13.7; 9.4 | 0.156 |
| SECONDARY Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase) |
2.14; 1.95; -0.78; 0.31 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase) |
22.62; 22.35; -11.44; -9.12 | 0.002 sig |
| SECONDARY Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase) |
55.5; 60.4; 77.8; 74.1 | 0.297 |
| SECONDARY Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase) |
2.1; 0.6 | 0.195 |
| SECONDARY Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase) |
3.6; 2.4; 0.0; 0.6 | 0.163 |
| SECONDARY Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase) |
0.6; 0.6; 0.6; 0.0 | 1.00 |
| SECONDARY Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase) |
0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Emergence of Mania During the Study (Acute Phase) |
0.6; 2.9 | 0.031 sig |
| SECONDARY Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) |
2.7; 1.2; 0.0; 0.0; 0.0; 0.0 | 0.269 |
| SECONDARY Change From Baseline to Endpoint in Blood Pressure (Acute Phase) |
112.39; 115.65; -0.99; -0.67; 112.35; 114.39 | 0.146 |
| SECONDARY Change From Baseline to Endpoint in Weight (Acute Phase) |
66.11; 68.30; 2.45; -0.13 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) |
5.11; 5.12; 0.10; 0.02; 4.83; 4.81 | 0.179 |
| SECONDARY Change From Baseline to Endpoint in Albumin (Acute Phase) |
43.07; 43.47; -0.81; 0.03 | 0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT) |
21.68; 21.18; 8.34; 0.00; 21.61; 20.25 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) |
2.45; 2.40; -0.21; 0.12; 9.74; 9.42 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase) |
4.65; 4.71; -0.05; 0.02 | 0.003 sig |
| SECONDARY Change From Baseline to Endpoint in Hematocrit (Acute Phase) |
0.42; 0.43; -0.01; 0.00 | 0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase) |
5.34; 5.37; 0.04; -0.03 | 0.009 sig |
| SECONDARY Change From Baseline to Endpoint in Hemoglobin (Acute Phase) |
8.65; 8.73; -0.11; 0.05 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Prolactin (Acute Phase) |
15.40; 15.86; 12.07; -1.18 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase) |
1.02; 1.02; -0.00; 0.00 | <0.001 sig |
| SECONDARY Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) |
406.85; 408.10; 2.82; 0.50; 415.79; 418.42 | 0.104 |
| SECONDARY Change From Baseline to Endpoint in Heart Rate (Acute Phase) |
69.63; 70.51; 3.49; 0.87 | 0.035 sig |
| SECONDARY Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase) |
2.09; 2.40; -0.42; -0.59 | 0.943 |
| SECONDARY Number of Participants With Adverse Events (Acute Phase) |
6; 7; 238; 88 | — |
| SECONDARY Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase) |
43.7 | — |
| SECONDARY Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase) |
85.1 | — |
| SECONDARY Percentage of Participants With Recovery (Open-Label Phase) |
69.9 | — |
| SECONDARY Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase) |
1.11; -0.03 | — |
| SECONDARY Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase) |
0.8 | — |
| SECONDARY Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase) |
0.8; 0.3; 0.0; 1.0 | — |
| SECONDARY Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) |
74.98; 0.15; 73.32; -0.03; 112.06; 0.96 | 0.736 |
| SECONDARY Change From Baseline to Endpoint in Weight (Open-Label Phase) |
68.31; 2.27 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase) |
42.64; 0.53; 73.24; 0.56 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase) |
68.58; 2.37; 107.36; -1.73; 28.90; 0.78 | 0.002 sig |
| SECONDARY Change From Baseline to Endpoint in Chloride (Open-Label Phase) |
103.62; 0.33 | 0.010 sig |
| SECONDARY Change From Baseline to Endpoint in Creatinine (Open-Label Phase) |
67.48; 2.05 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase) |
4.64; 0.03 | 0.021 sig |
| SECONDARY Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase) |
8.61; 0.04 | 0.035 sig |
| SECONDARY Change From Baseline to Endpoint in Platelet Count (Open-Label Phase) |
257.96; -4.56 | 0.024 sig |
| SECONDARY Change From Baseline to Endpoint in Prolactin (Open-Label Phase) |
21.64; -3.41 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Uric Acid (Open-Label Phase) |
324.74; 14.73 | <0.001 sig |
| SECONDARY Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) |
5.20; 0.06; 4.96; 0.05; 1.55; 0.10 | 0.047 sig |
| SECONDARY Change From Baseline to Endpoint in ECG (Open-Label Phase) |
410.09; 1.80; 421.72; 1.76 | 0.023 sig |
| SECONDARY Change From Baseline to Endpoint in Heart Rate (Open-Label Phase) |
71.85; 0.06 | 0.919 |
| SECONDARY Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase) |
1.3 | — |
| SECONDARY Number of Participants With Adverse Events (Open-Label Phase) |
14; 209 | — |
Summary
The purpose of this study is to assess whether olanzapine is superior to placebo in patients with bipolar depression.
Eligibility Criteria
Inclusion Criteria
- Each patient must be reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol, and must understand the nature of the study and have provided informed consent
- All female patients must test negative for pregnancy and females of breast-feeding potential must agree not to breastfeed an infant during the study and for 1 month following the last dose of study drug
- Patients must fulfill the criteria for a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) as well as criteria for bipolar I disorder, depressed, as defined in the DSM-IV-TR, based on clinical assessment and confirmed by the structured diagnostic interview, the Mini International Neuropsychiatric Interview (MINI), at study entry
- Patients must have a current 17-item Hamilton Depression Rating Scale (HAMD-17) score greater than or equal to 18 at Visit 1 and Visit 2
- Patients must have a current Young Mania Rating Scale (YMRS) total score less than or equal to 8 at Visit 2.
Exclusion Criteria
- Has received treatment within the past 30 days with a drug (not including study drug) that has not received regulatory approval for any indication at the time of study entry
- Has participated in a clinical trial of another investigational drug, including olanzapine, within 1 month (30 days) before study entry
- Was previously treated with olanzapine and had bipolar depression considered to be treatment-resistant to olanzapine or to olanzapine in combination with an available selective serotonin reuptake inhibitor (SSRI)
- Is experiencing (at the time of study entry) a current episode of bipolar depression that is greater than 90 days in duration
- Has been treatment-resistant to any therapy prescribed for bipolar depression when olanzapine alone or with an SSRI prescribed at an appropriate dose and duration
Data sourced from ClinicalTrials.gov (NCT00510146). 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.