Depression, Bipolar
Conditions
Brief summary
The purpose of this study is to assess whether olanzapine is superior to placebo in patients with bipolar depression.
Detailed description
1. Dose range and administration mode: Oral Olanzapine 5mg - 20mg/day 2. Duration: 1. Screening phase is 2-28 days. 2. Double-blind treatment phase is 6 weeks 3. Open-label extension phase is 18 weeks
Interventions
DRUGOlanzapine
5-20 mg, oral, once daily, for 24 weeks (participants randomized to olanzapine in double-blind treatment period) or 18 weeks (participants randomized to placebo in double-blind treatment period).
DRUGPlacebo
placebo tablets, oral, once daily at bedtime, 6 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase) | Baseline, Endpoint (Week 6) | The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase) | Baseline through Endpoint (Week 6) | Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Baseline, Endpoint (Week 6) | CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The score ranges from 1 (normal, not ill) to 7 (very seriously ill). |
| Number of Participants With Adverse Events (Open-Label Phase) | Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) | Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events. |
| Percentage of Participants With Recovery (Acute Phase) | Baseline through Endpoint (Week 6 ) | Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase) | Baseline, Endpoint (Week 6) | The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. |
| Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase) | Baseline, Endpoint (Week 6) | The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). |
| Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase) | Endpoint (Week 6) | In the MINI Major Depressive Episode module, participants are asked a series of Yes/No questions to determine whether or not they are experiencing a major depressive episode or a major depressive episode with melancholic features. |
| Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase) | Endpoint (Week 6) | In the MINI Manic Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing hypomanic or manic episodes. |
| Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase) | Endpoint (Week 6) | In the MINI Psychotic Features Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing mood disorder with psychotic features or current psychotic disorders. |
| Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase) | Endpoint (Week 6) | In the MINI Alcohol Abuse and Dependence Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current alcohol dependence or abuse. |
| Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase) | Endpoint (Week 6) | In the MINI Substance Dependence and Abuse Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current non-alcohol substance use dependence or abuse. |
| Percentage of Participants With Emergence of Mania During the Study (Acute Phase) | Baseline through Endpoint (Week 6) | Emergence of mania is defined as first occurrence of score of \>=15 in the YMRS total score in the post-baseline period of Acute Phase. The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. |
| Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Endpoint (Week 6) | EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not \>=3 on 1 item nor \>=2 on 2 items; abnormal endpoint is defined as a score \>=3 on 1 item or \>=2 on 2 items, or an increase of 3 on Parkinsonism total. Baseline akathisia, dystonia and dyskinesia is defined as a score \<2; abnormal endpoint is a score \>=2 or an increase \>= 2 from that baseline score. |
| Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Weight (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Albumin (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| 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) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Hematocrit (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Hemoglobin (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Prolactin (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Baseline, Endpoint (Week 6) | Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval). |
| Change From Baseline to Endpoint in Heart Rate (Acute Phase) | Baseline, Endpoint (Week 6) | — |
| Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase) | Baseline, Endpoint (Week 6) | The MINI module C (MINI-C) is a rating scale for severity of suicidal thoughts and behaviors. The MINI-C is composed of 12 Yes/No questions with variable scores assigned to each question. The scale ranges from 0 to 52 with higher scores indicating a greater presence of suicidal thoughts and/or behaviors. |
| Number of Participants With Adverse Events (Acute Phase) | Baseline through Week 6 (Acute Phase) | Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events. |
| Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase) | Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) | The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score. |
| Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase) | Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) | Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Percentage of Participants With Recovery (Open-Label Phase) | Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) | Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. |
| Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase) | Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) | Emergence of mania is defined as first occurrence of score of \>=15 in the YMRS total score in the Open-Label Extension. The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. |
| Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase) | Endpoint (Week 24) | EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not \>=3 on 1 item nor \>=2 on 2 items; abnormal endpoint is defined as a score \>=3 on 1 item or \>=2 on 2 items, or an increase of 3 on Parkinsonism total. Baseline akathisia, dystonia and dyskinesia is defined as a score \<2; abnormal endpoint is a score \>=2 or an increase \>= 2 from that baseline score. |
| Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Weight (Open-Label Phase) | Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Chloride (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Creatinine (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Platelet Count (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase) | Endpoint (Week 6) | Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
| Change From Baseline to Endpoint in Uric Acid (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Change From Baseline to Endpoint in ECG (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval). |
| Change From Baseline to Endpoint in Heart Rate (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
| Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase) | Endpoint (Week 24) | The MINI module C (MINI-C) is a rating scale for severity of suicidal thoughts and behaviors. The MINI-C is composed of 12 Yes/No questions with variable scores assigned to each question. The scale ranges from 0 to 52 with higher scores indicating a greater presence of suicidal thoughts and/or behaviors. Based upon scores, suicidality is defined as Low (1-8), Medium (9-16), and High (\>=17). |
| Change From Baseline to Endpoint in Prolactin (Open-Label Phase) | Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) | — |
Countries
China, Japan, South Korea
Participant flow
Pre-assignment details
Study Period I (2-28 days) included screening and lead-in period for discontinuation of excluded medications at least 25 hours before day of randomization. Study Period II was 6-week, double-blind (Acute Phase) of treatment. Study Period III was 18-week, open-label extension for those who completed Study Period II.
Participants by arm
| Arm | Count |
|---|---|
| Olanzapine During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation. | 343 |
| Placebo Matching placebo administered once daily, by mouth during double-blind treatment. | 171 |
| Total | 514 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment | Adverse Event | 30 | 13 |
| Double-Blind Treatment | Clinical Relapse | 0 | 1 |
| Double-Blind Treatment | Entry Criteria Not Met | 3 | 0 |
| Double-Blind Treatment | Lack of Efficacy | 6 | 13 |
| Double-Blind Treatment | Lost to Follow-up | 3 | 7 |
| Double-Blind Treatment | Physician Decision | 6 | 0 |
| Double-Blind Treatment | Protocol Violation | 1 | 2 |
| Double-Blind Treatment | Withdrawal by Subject | 27 | 13 |
| Open-Label Treatment | Adverse Event | 22 | 8 |
| Open-Label Treatment | Clinical Relapse | 1 | 1 |
| Open-Label Treatment | Death | 1 | 1 |
| Open-Label Treatment | Lack of Efficacy | 4 | 0 |
| Open-Label Treatment | Lost to Follow-up | 10 | 1 |
| Open-Label Treatment | Physician Decision | 3 | 1 |
| Open-Label Treatment | Protocol Violation | 4 | 2 |
| Open-Label Treatment | Sponsor Decision | 2 | 0 |
| Open-Label Treatment | Withdrawal by Subject | 24 | 12 |
Baseline characteristics
| Characteristic | Olanzapine | Total | Placebo |
|---|---|---|---|
| Age at onset, Bipolar I Disorder | 27.57 years STANDARD_DEVIATION 10.98 | 27.09 years STANDARD_DEVIATION 10.64 | 26.12 years STANDARD_DEVIATION 9.9 |
| Age Continuous | 35.93 years STANDARD_DEVIATION 11.13 | 35.61 years STANDARD_DEVIATION 11.09 | 34.96 years STANDARD_DEVIATION 11.02 |
| Race/Ethnicity, Customized African | 18 participants | 22 participants | 4 participants |
| Race/Ethnicity, Customized Caucasian | 36 participants | 58 participants | 22 participants |
| Race/Ethnicity, Customized East Asian | 282 participants | 423 participants | 141 participants |
| Race/Ethnicity, Customized Hispanic | 6 participants | 9 participants | 3 participants |
| Race/Ethnicity, Customized Native American | 1 participants | 2 participants | 1 participants |
| Region of Enrollment China | 140 participants | 210 participants | 70 participants |
| Region of Enrollment Japan | 104 participants | 156 participants | 52 participants |
| Region of Enrollment Korea, Republic of | 20 participants | 30 participants | 10 participants |
| Region of Enrollment Taiwan | 19 participants | 28 participants | 9 participants |
| Region of Enrollment United States | 60 participants | 90 participants | 30 participants |
| Sex: Female, Male Female | 205 Participants | 300 Participants | 95 Participants |
| Sex: Female, Male Male | 138 Participants | 214 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 238 / 343 | 88 / 171 | 209 / 389 |
| serious Total, serious adverse events | 6 / 343 | 7 / 171 | 14 / 389 |
Outcome results
Primary
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)
The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Baseline, Endpoint (Week 6)
Population: Intention-to-treat population (ITT) with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase) | Baseline | 29.36 units on a scale | Standard Deviation 5.71 |
| Olanzapine | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase) | Change | -14.26 units on a scale | Standard Deviation 9.73 |
| Placebo | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase) | Baseline | 28.69 units on a scale | Standard Deviation 6.33 |
| Placebo | Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase) | Change | -11.71 units on a scale | Standard Deviation 11.09 |
p-value: 0.01895% CI: [-3.93, -0.36]ANCOVA
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)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | 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) | Baseline (ALT/SGPT) | 21.68 units/Liter | Standard Deviation 16.53 |
| Olanzapine | 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) | Change (ALT/SGPT) | 8.34 units/Liter | Standard Deviation 26.9 |
| Olanzapine | 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) | Baseline (AST/SGOT) | 21.61 units/Liter | Standard Deviation 8.34 |
| Olanzapine | 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) | Change (AST/SGOT) | 4.31 units/Liter | Standard Deviation 15.66 |
| Olanzapine | 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) | Baseline (GGT) | 24.87 units/Liter | Standard Deviation 36.59 |
| Olanzapine | 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) | Change (GGT) | 5.36 units/Liter | Standard Deviation 22.7 |
| Placebo | 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) | Baseline (GGT) | 23.63 units/Liter | Standard Deviation 23.17 |
| Placebo | 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) | Baseline (ALT/SGPT) | 21.18 units/Liter | Standard Deviation 13.17 |
| Placebo | 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) | Change (AST/SGOT) | 1.26 units/Liter | Standard Deviation 11.06 |
| Placebo | 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) | Change (ALT/SGPT) | 0.00 units/Liter | Standard Deviation 13.63 |
| Placebo | 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) | Change (GGT) | -1.21 units/Liter | Standard Deviation 11.67 |
| Placebo | 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) | Baseline (AST/SGOT) | 20.25 units/Liter | Standard Deviation 6.7 |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Albumin (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Albumin (Acute Phase) | Baseline | 43.07 gram/Liter | Standard Deviation 3.85 |
| Olanzapine | Change From Baseline to Endpoint in Albumin (Acute Phase) | Change | -0.81 gram/Liter | Standard Deviation 2.89 |
| Placebo | Change From Baseline to Endpoint in Albumin (Acute Phase) | Baseline | 43.47 gram/Liter | Standard Deviation 3.69 |
| Placebo | Change From Baseline to Endpoint in Albumin (Acute Phase) | Change | 0.03 gram/Liter | Standard Deviation 3.11 |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase) | Baseline- Albumin | 42.64 gram/Liter | Standard Deviation 3.58 |
| Olanzapine | Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase) | Change- Albumin | 0.53 gram/Liter | Standard Deviation 2.86 |
| Olanzapine | Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase) | Baseline- Total Protein | 73.24 gram/Liter | Standard Deviation 4.39 |
| Olanzapine | Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase) | Change- Total Protein | 0.56 gram/Liter | Standard Deviation 3.78 |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase) | Baseline- Alkaline Phosphatase | 68.58 units/Liter | Standard Deviation 19.33 |
| Olanzapine | Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase) | Change- Alkaline Phosphatase | 2.37 units/Liter | Standard Deviation 12.85 |
| Olanzapine | Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase) | Baseline- CPK | 107.36 units/Liter | Standard Deviation 133.21 |
| Olanzapine | Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase) | Change- CPK | -1.73 units/Liter | Standard Deviation 124.56 |
| Olanzapine | Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase) | Baseline- GGT | 28.90 units/Liter | Standard Deviation 32.08 |
| Olanzapine | Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase) | Change- GGT | 0.78 units/Liter | Standard Deviation 25.9 |
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.01Wilcoxon (Mann-Whitney)
p-value: 0.354Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Standing Systolic (N=320, 159) | 112.39 mmHg (millimeters of mercury) | Standard Deviation 13.25 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Standing Systolic (N=320, 159) | -0.99 mmHg (millimeters of mercury) | Standard Deviation 10.83 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Sitting Systolic (N=340, 169) | 112.35 mmHg (millimeters of mercury) | Standard Deviation 13.42 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Sitting Systolic (N=340, 169) | -0.36 mmHg (millimeters of mercury) | Standard Deviation 11.1 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Standing Diastolic (N=320, 159) | 74.77 mmHg (millimeters of mercury) | Standard Deviation 10.2 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Standing Diastolic (N=320, 159) | -0.48 mmHg (millimeters of mercury) | Standard Deviation 8.71 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Sitting Diastolic (N=340, 169) | 73.07 mmHg (millimeters of mercury) | Standard Deviation 9.93 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Sitting Diastolic (N=340, 169) | -0.11 mmHg (millimeters of mercury) | Standard Deviation 9.37 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Orthostatic Change-Systolic (N=320, 159) | 0.54 mmHg (millimeters of mercury) | Standard Deviation 6.51 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Orthostatic Change-Systolic (N=320, 159) | -0.65 mmHg (millimeters of mercury) | Standard Deviation 8.2 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Orthostatic Change-Diastolic (N=320, 159 | 1.92 mmHg (millimeters of mercury) | Standard Deviation 5.93 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Orthostatic Change-Diastolic (N=320, 159) | -0.52 mmHg (millimeters of mercury) | Standard Deviation 6.79 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Orthostatic Change-Diastolic (N=320, 159 | 2.96 mmHg (millimeters of mercury) | Standard Deviation 5.57 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Standing Systolic (N=320, 159) | 115.65 mmHg (millimeters of mercury) | Standard Deviation 14.39 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Sitting Diastolic (N=340, 169) | 73.92 mmHg (millimeters of mercury) | Standard Deviation 9.86 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Standing Systolic (N=320, 159) | -0.67 mmHg (millimeters of mercury) | Standard Deviation 11.18 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Orthostatic Change-Systolic (N=320, 159) | -0.45 mmHg (millimeters of mercury) | Standard Deviation 11.45 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Sitting Systolic (N=340, 169) | 114.39 mmHg (millimeters of mercury) | Standard Deviation 13.67 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Sitting Diastolic (N=340, 169) | 0.39 mmHg (millimeters of mercury) | Standard Deviation 9.08 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Sitting Systolic (N=340, 169) | 0.04 mmHg (millimeters of mercury) | Standard Deviation 12.16 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Orthostatic Change-Diastolic (N=320, 159) | -0.47 mmHg (millimeters of mercury) | Standard Deviation 6.78 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Standing Diastolic (N=320, 159) | 76.87 mmHg (millimeters of mercury) | Standard Deviation 10.26 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Baseline- Orthostatic Change-Systolic (N=320, 159) | 1.21 mmHg (millimeters of mercury) | Standard Deviation 7.67 |
| Placebo | Change From Baseline to Endpoint in Blood Pressure (Acute Phase) | Change- Standing Diastolic (N=320, 159) | -0.14 mmHg (millimeters of mercury) | Standard Deviation 8.44 |
p-value: 0.146ANCOVA
p-value: 0.249ANCOVA
p-value: 0.146ANCOVA
p-value: 0.271ANCOVA
p-value: 0.284ANCOVA
p-value: 0.067ANCOVA
Secondary
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Baseline-Standing Diastolic (N=361) | 74.98 millimeters of mercury | Standard Deviation 10.77 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Change- Standing Diastolic (N=361) | 0.15 millimeters of mercury | Standard Deviation 8.28 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Baseline- Sitting Diastolic (N=383) | 73.32 millimeters of mercury | Standard Deviation 10.73 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Change- Sitting Diastolic (N=383) | -0.03 millimeters of mercury | Standard Deviation 8.68 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Baseline- Standing Systolic (N=361) | 112.06 millimeters of mercury | Standard Deviation 14.58 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Change- Standing Systolic (N=361) | 0.96 millimeters of mercury | Standard Deviation 10.37 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Baseline- Sitting Systolic (N=383) | 112.26 millimeters of mercury | Standard Deviation 14.45 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Change- Sitting Systolic (N=383) | 0.27 millimeters of mercury | Standard Deviation 10.28 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Baseline- Orthostatic Change-Diastolic (N=358) | 1.75 millimeters of mercury | Standard Deviation 5.25 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Change- Orthostatic Change- Diastolic (N=358) | 0.16 millimeters of mercury | Standard Deviation 6.56 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Baseline- Orthostatic Change- Systolic (N=358) | 0.19 millimeters of mercury | Standard Deviation 6.19 |
| Olanzapine | Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase) | Change- Orthostatic Change- Systolic (N=358) | 0.65 millimeters of mercury | Standard Deviation 7.92 |
p-value: 0.736t-test, 2 sided
p-value: 0.944t-test, 2 sided
p-value: 0.08t-test, 2 sided
p-value: 0.612t-test, 2 sided
p-value: 0.64t-test, 2 sided
p-value: 0.122t-test, 2 sided
Secondary
Change From Baseline to Endpoint in Chloride (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Chloride (Open-Label Phase) | Baseline | 103.62 millimole/Liter | Standard Deviation 2.16 |
| Olanzapine | Change From Baseline to Endpoint in Chloride (Open-Label Phase) | Change | 0.33 millimole/Liter | Standard Deviation 2.38 |
p-value: 0.01Wilcoxon (Mann-Whitney)
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)
CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The score ranges from 1 (normal, not ill) to 7 (very seriously ill).
Time frame: Baseline, Endpoint (Week 6)
Population: Intention-to-treat population (ITT) with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Baseline-Mania | 1.07 units on a scale | Standard Deviation 0.29 |
| Olanzapine | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Change-Mania | 0.00 units on a scale | Standard Deviation 0.43 |
| Olanzapine | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Baseline-Depression | 4.54 units on a scale | Standard Deviation 0.73 |
| Olanzapine | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Change-Depression | -1.45 units on a scale | Standard Deviation 1.26 |
| Olanzapine | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Baseline- Overall | 4.45 units on a scale | Standard Deviation 0.79 |
| Olanzapine | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Change- Overall | -1.40 units on a scale | Standard Deviation 1.28 |
| Placebo | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Baseline- Overall | 4.44 units on a scale | Standard Deviation 0.79 |
| Placebo | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Baseline-Mania | 1.11 units on a scale | Standard Deviation 0.35 |
| Placebo | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Change-Depression | -1.20 units on a scale | Standard Deviation 1.36 |
| Placebo | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Change-Mania | 0.09 units on a scale | Standard Deviation 0.59 |
| Placebo | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Change- Overall | -1.08 units on a scale | Standard Deviation 1.27 |
| Placebo | Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase) | Baseline-Depression | 4.53 units on a scale | Standard Deviation 0.73 |
p-value: 0.00895% CI: [-0.2, -0.03]ANCOVA
p-value: 0.03795% CI: [-0.47, -0.01]ANCOVA
p-value: 0.00895% CI: [-0.53, -0.08]ANCOVA
Secondary
Change From Baseline to Endpoint in Creatinine (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Creatinine (Open-Label Phase) | Baseline | 67.48 micromole/Liter | Standard Deviation 14.98 |
| Olanzapine | Change From Baseline to Endpoint in Creatinine (Open-Label Phase) | Change | 2.05 micromole/Liter | Standard Deviation 7.9 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Baseline- Direct Bilirubin | 2.45 micromole/Liter | Standard Deviation 1.23 |
| Olanzapine | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Change- Direct Bilirubin | -0.21 micromole/Liter | Standard Deviation 1.03 |
| Olanzapine | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Baseline- Total Bilirubin | 9.74 micromole/Liter | Standard Deviation 5.18 |
| Olanzapine | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Change- Total Bilirubin | -0.68 micromole/Liter | Standard Deviation 4.57 |
| Olanzapine | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Baseline- Uric Acid | 307.19 micromole/Liter | Standard Deviation 92.03 |
| Olanzapine | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Change- Uric Acid | 19.55 micromole/Liter | Standard Deviation 51.1 |
| Placebo | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Baseline- Uric Acid | 314.38 micromole/Liter | Standard Deviation 86.69 |
| Placebo | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Baseline- Direct Bilirubin | 2.40 micromole/Liter | Standard Deviation 1.08 |
| Placebo | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Change- Total Bilirubin | 0.47 micromole/Liter | Standard Deviation 4.27 |
| Placebo | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Change- Direct Bilirubin | 0.12 micromole/Liter | Standard Deviation 1.02 |
| Placebo | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Change- Uric Acid | -1.86 micromole/Liter | Standard Deviation 50.37 |
| Placebo | Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase) | Baseline- Total Bilirubin | 9.42 micromole/Liter | Standard Deviation 4.58 |
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in ECG (Open-Label Phase)
Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval).
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in ECG (Open-Label Phase) | Baseline- QTcF | 410.09 milliseconds | Standard Deviation 19.44 |
| Olanzapine | Change From Baseline to Endpoint in ECG (Open-Label Phase) | Change- QTcF | 1.80 milliseconds | Standard Deviation 15.07 |
| Olanzapine | Change From Baseline to Endpoint in ECG (Open-Label Phase) | Baseline- QTcB | 421.72 milliseconds | Standard Deviation 19.61 |
| Olanzapine | Change From Baseline to Endpoint in ECG (Open-Label Phase) | Change- QTcB | 1.76 milliseconds | Standard Deviation 16.69 |
p-value: 0.023t-test, 2 sided
p-value: 0.044t-test, 2 sided
Secondary
Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase) | Baseline | 4.65 trillion cells per liter ( TRIL/L) | Standard Deviation 0.51 |
| Olanzapine | Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase) | Change | -0.05 trillion cells per liter ( TRIL/L) | Standard Deviation 0.27 |
| Placebo | Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase) | Baseline | 4.71 trillion cells per liter ( TRIL/L) | Standard Deviation 0.52 |
| Placebo | Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase) | Change | 0.02 trillion cells per liter ( TRIL/L) | Standard Deviation 0.27 |
p-value: 0.003Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase) | Baseline | 4.64 trillion cells per liter (Tril/L) | Standard Deviation 0.53 |
| Olanzapine | Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase) | Change | 0.03 trillion cells per liter (Tril/L) | Standard Deviation 0.3 |
p-value: 0.021Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline- Fasting Glucose (N=320, 155) | 5.11 millimole/Liter | Standard Deviation 0.58 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- Fasting Glucose (N=320, 155) | 0.10 millimole/Liter | Standard Deviation 0.61 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline- Cholesterol (N=329, 160) | 4.83 millimole/Liter | Standard Deviation 1.01 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- Cholesterol (N=329, 160) | 0.24 millimole/Liter | Standard Deviation 0.76 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline-Triglycerides (N=329, 160) | 1.39 millimole/Liter | Standard Deviation 0.85 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- Triglycerides (N=329, 160) | 0.26 millimole/Liter | Standard Deviation 0.97 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline- LDL Cholesterol (N=328, 159) | 2.77 millimole/Liter | Standard Deviation 0.87 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- LDL Cholesterol (N=328, 159) | 0.17 millimole/Liter | Standard Deviation 0.66 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline- HDL Cholesterol (N=329, 160) | 1.43 millimole/Liter | Standard Deviation 0.41 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- HDL Cholesterol (N=329, 160) | -0.03 millimole/Liter | Standard Deviation 0.25 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- LDL Cholesterol (N=328, 159) | -0.09 millimole/Liter | Standard Deviation 0.48 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline- Fasting Glucose (N=320, 155) | 5.12 millimole/Liter | Standard Deviation 0.57 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- Triglycerides (N=329, 160) | 0.03 millimole/Liter | Standard Deviation 0.71 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- Fasting Glucose (N=320, 155) | 0.02 millimole/Liter | Standard Deviation 0.54 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- HDL Cholesterol (N=329, 160) | 0.02 millimole/Liter | Standard Deviation 0.21 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline- Cholesterol (N=329, 160) | 4.81 millimole/Liter | Standard Deviation 1 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline- LDL Cholesterol (N=328, 159) | 2.83 millimole/Liter | Standard Deviation 0.84 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Change- Cholesterol (N=329, 160) | -0.07 millimole/Liter | Standard Deviation 0.49 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline- HDL Cholesterol (N=329, 160) | 1.36 millimole/Liter | Standard Deviation 0.35 |
| Placebo | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) | Baseline-Triglycerides (N=329, 160) | 1.34 millimole/Liter | Standard Deviation 0.8 |
p-value: 0.179ANCOVA
p-value: <0.001ANCOVA
p-value: 0.003ANCOVA
p-value: <0.001ANCOVA
p-value: 0.095ANCOVA
Secondary
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Change- Triglycerides (N=380) | 0.10 millimole/Liter | Standard Deviation 0.97 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Baseline- LDL Cholesterol (N=378) | 2.88 millimole/Liter | Standard Deviation 0.91 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Baseline- Fasting Glucose (N=375) | 5.20 millimole/Liter | Standard Deviation 0.57 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Change- Fasting Glucose (N=375) | 0.06 millimole/Liter | Standard Deviation 0.63 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Baseline- Cholesterol (N=380) | 4.96 millimole/Liter | Standard Deviation 1.08 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Change- Cholesterol (N=380) | 0.05 millimole/Liter | Standard Deviation 0.7 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Baseline- Triglycerides (N=380) | 1.55 millimole/Liter | Standard Deviation 1.06 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Change- LDL Cholesterol (N=378) | 0.06 millimole/Liter | Standard Deviation 0.63 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Baseline- HDL Cholesterol (N=380) | 1.39 millimole/Liter | Standard Deviation 0.4 |
| Olanzapine | Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase) | Change- HDL Cholesterol (N=380) | -0.05 millimole/Liter | Standard Deviation 0.24 |
p-value: 0.047t-test, 2 sided
p-value: 0.13t-test, 2 sided
p-value: 0.055t-test, 2 sided
p-value: 0.049t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)
The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time frame: Baseline, Endpoint (Week 6)
Population: Intention-to-treat population (ITT) with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase) | Baseline | 22.62 units on a scale | Standard Deviation 3.47 |
| Olanzapine | Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase) | Change | -11.44 units on a scale | Standard Deviation 7.02 |
| Placebo | Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase) | Baseline | 22.35 units on a scale | Standard Deviation 3.53 |
| Placebo | Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase) | Change | -9.12 units on a scale | Standard Deviation 7.99 |
p-value: 0.00295% CI: [-3.61, -0.81]ANCOVA
Secondary
Change From Baseline to Endpoint in Heart Rate (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Heart Rate (Acute Phase) | Baseline | 69.63 beats per minute (bpm) | Standard Deviation 12.65 |
| Olanzapine | Change From Baseline to Endpoint in Heart Rate (Acute Phase) | Change | 3.49 beats per minute (bpm) | Standard Deviation 11.18 |
| Placebo | Change From Baseline to Endpoint in Heart Rate (Acute Phase) | Baseline | 70.51 beats per minute (bpm) | Standard Deviation 11.94 |
| Placebo | Change From Baseline to Endpoint in Heart Rate (Acute Phase) | Change | 0.87 beats per minute (bpm) | Standard Deviation 11.51 |
p-value: 0.035ANCOVA
Secondary
Change From Baseline to Endpoint in Heart Rate (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Heart Rate (Open-Label Phase) | Baseline | 71.85 beats per minute | Standard Deviation 11.64 |
| Olanzapine | Change From Baseline to Endpoint in Heart Rate (Open-Label Phase) | Change | 0.06 beats per minute | Standard Deviation 10.79 |
p-value: 0.919t-test, 2 sided
Secondary
Change From Baseline to Endpoint in Hematocrit (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Hematocrit (Acute Phase) | Baseline | 0.42 proportion of blood volume | Standard Deviation 0.04 |
| Olanzapine | Change From Baseline to Endpoint in Hematocrit (Acute Phase) | Change | -0.01 proportion of blood volume | Standard Deviation 0.03 |
| Placebo | Change From Baseline to Endpoint in Hematocrit (Acute Phase) | Baseline | 0.43 proportion of blood volume | Standard Deviation 0.05 |
| Placebo | Change From Baseline to Endpoint in Hematocrit (Acute Phase) | Change | 0.00 proportion of blood volume | Standard Deviation 0.03 |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase) | Baseline | 5.34 percent of glycosylated hemoglobin | Standard Deviation 0.37 |
| Olanzapine | Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase) | Change | 0.04 percent of glycosylated hemoglobin | Standard Deviation 0.26 |
| Placebo | Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase) | Change | -0.03 percent of glycosylated hemoglobin | Standard Deviation 0.28 |
| Placebo | Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase) | Baseline | 5.37 percent of glycosylated hemoglobin | Standard Deviation 0.37 |
p-value: 0.009Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Hemoglobin (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Hemoglobin (Acute Phase) | Baseline | 8.65 millimole/Liter of iron (Fe) | Standard Deviation 0.99 |
| Olanzapine | Change From Baseline to Endpoint in Hemoglobin (Acute Phase) | Change | -0.11 millimole/Liter of iron (Fe) | Standard Deviation 0.5 |
| Placebo | Change From Baseline to Endpoint in Hemoglobin (Acute Phase) | Baseline | 8.73 millimole/Liter of iron (Fe) | Standard Deviation 0.97 |
| Placebo | Change From Baseline to Endpoint in Hemoglobin (Acute Phase) | Change | 0.05 millimole/Liter of iron (Fe) | Standard Deviation 0.5 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase) | Baseline | 8.61 millimole/Liter of iron (Fe) | Standard Deviation 1.01 |
| Olanzapine | Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase) | Change | 0.04 millimole/Liter of iron (Fe) | Standard Deviation 0.51 |
p-value: 0.035Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)
The MINI module C (MINI-C) is a rating scale for severity of suicidal thoughts and behaviors. The MINI-C is composed of 12 Yes/No questions with variable scores assigned to each question. The scale ranges from 0 to 52 with higher scores indicating a greater presence of suicidal thoughts and/or behaviors.
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase) | Baseline | 2.09 units on a scale | Standard Deviation 3.44 |
| Olanzapine | Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase) | Change | -0.42 units on a scale | Standard Deviation 3.71 |
| Placebo | Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase) | Baseline | 2.40 units on a scale | Standard Deviation 3.49 |
| Placebo | Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase) | Change | -0.59 units on a scale | Standard Deviation 3.44 |
p-value: 0.94395% CI: [-0.59, 0.64]ANCOVA
Secondary
Change From Baseline to Endpoint in Platelet Count (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Platelet Count (Open-Label Phase) | Baseline | 257.96 billion cells per liter (BILL/L) | Standard Deviation 64.25 |
| Olanzapine | Change From Baseline to Endpoint in Platelet Count (Open-Label Phase) | Change | -4.56 billion cells per liter (BILL/L) | Standard Deviation 49.94 |
p-value: 0.024Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Prolactin (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Prolactin (Acute Phase) | Baseline | 15.40 microgram/Liter | Standard Deviation 16.89 |
| Olanzapine | Change From Baseline to Endpoint in Prolactin (Acute Phase) | Change | 12.07 microgram/Liter | Standard Deviation 24 |
| Placebo | Change From Baseline to Endpoint in Prolactin (Acute Phase) | Baseline | 15.86 microgram/Liter | Standard Deviation 21.54 |
| Placebo | Change From Baseline to Endpoint in Prolactin (Acute Phase) | Change | -1.18 microgram/Liter | Standard Deviation 26.49 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Prolactin (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Prolactin (Open-Label Phase) | Baseline | 21.64 microgram/Liter | Standard Deviation 18.48 |
| Olanzapine | Change From Baseline to Endpoint in Prolactin (Open-Label Phase) | Change | -3.41 microgram/Liter | Standard Deviation 17.2 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Uric Acid (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Uric Acid (Open-Label Phase) | Baseline | 324.74 micromole/Liter | Standard Deviation 89.39 |
| Olanzapine | Change From Baseline to Endpoint in Uric Acid (Open-Label Phase) | Change | 14.73 micromole/Liter | Standard Deviation 56.8 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase) | Baseline | 1.02 ratio | Standard Deviation 0.01 |
| Olanzapine | Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase) | Change | -0.00 ratio | Standard Deviation 0.01 |
| Placebo | Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase) | Baseline | 1.02 ratio | Standard Deviation 0.01 |
| Placebo | Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase) | Change | 0.00 ratio | Standard Deviation 0.01 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Endpoint in Weight (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Weight (Acute Phase) | Baseline | 66.11 kilograms | Standard Deviation 18.11 |
| Olanzapine | Change From Baseline to Endpoint in Weight (Acute Phase) | Endpoint | 2.45 kilograms | Standard Deviation 2.82 |
| Placebo | Change From Baseline to Endpoint in Weight (Acute Phase) | Baseline | 68.30 kilograms | Standard Deviation 18.73 |
| Placebo | Change From Baseline to Endpoint in Weight (Acute Phase) | Endpoint | -0.13 kilograms | Standard Deviation 2.1 |
p-value: <0.001ANCOVA
Secondary
Change From Baseline to Endpoint in Weight (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Weight (Open-Label Phase) | Baseline | 68.31 kilograms | Standard Deviation 18.54 |
| Olanzapine | Change From Baseline to Endpoint in Weight (Open-Label Phase) | Change | 2.27 kilograms | Standard Deviation 4 |
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase)
The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.
Time frame: Baseline, Endpoint (Week 6)
Population: Intention-to-treat population (ITT) with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase) | Baseline | 2.14 units on a scale | Standard Deviation 2.1 |
| Olanzapine | Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase) | Change | -0.78 units on a scale | Standard Deviation 2.56 |
| Placebo | Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase) | Baseline | 1.95 units on a scale | Standard Deviation 2.18 |
| Placebo | Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase) | Change | 0.31 units on a scale | Standard Deviation 4.21 |
p-value: <0.00195% CI: [-1.56, -0.43]ANCOVA
Secondary
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase)
The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase) | Baseline | 1.11 units on a scale | Standard Deviation 2.87 |
| Olanzapine | Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase) | Change | -0.03 units on a scale | Standard Deviation 2.55 |
Secondary
Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval).
Time frame: Baseline, Endpoint (Week 6)
Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Baseline- QTcF | 406.85 milliseconds | Standard Deviation 19.53 |
| Olanzapine | Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Change- QTcF | 2.82 milliseconds | Standard Deviation 14.21 |
| Olanzapine | Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Baseline- QTcB | 415.79 milliseconds | Standard Deviation 20.55 |
| Olanzapine | Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Change- QTcB | 6.58 milliseconds | Standard Deviation 18.01 |
| Placebo | Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Change- QTcB | 1.21 milliseconds | Standard Deviation 16.02 |
| Placebo | Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Baseline- QTcF | 408.10 milliseconds | Standard Deviation 18.72 |
| Placebo | Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Baseline- QTcB | 418.42 milliseconds | Standard Deviation 19.95 |
| Placebo | Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase) | Change- QTcF | 0.50 milliseconds | Standard Deviation 12.27 |
p-value: 0.104ANCOVA
p-value: 0.006ANCOVA
Secondary
Number of Participants With Adverse Events (Acute Phase)
Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events.
Time frame: Baseline through Week 6 (Acute Phase)
Population: All enrolled participants in Acute Phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Number of Participants With Adverse Events (Acute Phase) | Serious | 6 participants |
| Olanzapine | Number of Participants With Adverse Events (Acute Phase) | Non-Serious | 238 participants |
| Placebo | Number of Participants With Adverse Events (Acute Phase) | Serious | 7 participants |
| Placebo | Number of Participants With Adverse Events (Acute Phase) | Non-Serious | 88 participants |
Secondary
Number of Participants With Adverse Events (Open-Label Phase)
Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events.
Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Population: Total participants in the open-label extension phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Number of Participants With Adverse Events (Open-Label Phase) | Serious | 14 participants |
| Olanzapine | Number of Participants With Adverse Events (Open-Label Phase) | Non-Serious | 209 participants |
Secondary
Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)
In the MINI Alcohol Abuse and Dependence Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current alcohol dependence or abuse.
Time frame: Endpoint (Week 6)
Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase) | Dependence | 0.6 percentage of participants |
| Olanzapine | Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase) | Abuse | 0.6 percentage of participants |
| Placebo | Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase) | Dependence | 0.6 percentage of participants |
| Placebo | Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase) | Abuse | 0.0 percentage of participants |
p-value: 1Cochran-Mantel-Haenszel
p-value: 0.324Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase)
In the MINI Manic Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing hypomanic or manic episodes.
Time frame: Endpoint (Week 6)
Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase) | 2.1 percentage of participants |
| Placebo | Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase) | 0.6 percentage of participants |
p-value: 0.195Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Emergence of Mania During the Study (Acute Phase)
Emergence of mania is defined as first occurrence of score of \>=15 in the YMRS total score in the post-baseline period of Acute Phase. The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.
Time frame: Baseline through Endpoint (Week 6)
Population: Intention-to-treat (ITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Emergence of Mania During the Study (Acute Phase) | 0.6 percentage of participants |
| Placebo | Percentage of Participants With Emergence of Mania During the Study (Acute Phase) | 2.9 percentage of participants |
p-value: 0.031Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase)
Emergence of mania is defined as first occurrence of score of \>=15 in the YMRS total score in the Open-Label Extension. The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.
Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Population: Total participants in the open-label extension phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase) | 0.8 percentage of participants |
Secondary
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)
EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not \>=3 on 1 item nor \>=2 on 2 items; abnormal endpoint is defined as a score \>=3 on 1 item or \>=2 on 2 items, or an increase of 3 on Parkinsonism total. Baseline akathisia, dystonia and dyskinesia is defined as a score \<2; abnormal endpoint is a score \>=2 or an increase \>= 2 from that baseline score.
Time frame: Endpoint (Week 6)
Population: Participants with a normal baseline and an endpoint result.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Akathisia (N=335, 169) | 2.7 percentage of participants |
| Olanzapine | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Dyskinesia (N=337, 169) | 0.0 percentage of participants |
| Olanzapine | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Dystonia (N=337, 169) | 0.0 percentage of participants |
| Olanzapine | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Parkinsonism (N=337, 169) | 0.9 percentage of participants |
| Placebo | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Parkinsonism (N=337, 169) | 0.6 percentage of participants |
| Placebo | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Akathisia (N=335, 169) | 1.2 percentage of participants |
| Placebo | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Dystonia (N=337, 169) | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase) | Dyskinesia (N=337, 169) | 0.0 percentage of participants |
p-value: 0.269Cochran-Mantel-Haenszel
p-value: 0.736Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)
EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not \>=3 on 1 item nor \>=2 on 2 items; abnormal endpoint is defined as a score \>=3 on 1 item or \>=2 on 2 items, or an increase of 3 on Parkinsonism total. Baseline akathisia, dystonia and dyskinesia is defined as a score \<2; abnormal endpoint is a score \>=2 or an increase \>= 2 from that baseline score.
Time frame: Endpoint (Week 24)
Population: Participants who entered Open-Label Phase with a normal baseline and at least one post-baseline result.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase) | Akathisia (N=378) | 0.8 percentage of participants |
| Olanzapine | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase) | Dyskinesia (N=385) | 0.3 percentage of participants |
| Olanzapine | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase) | Dystonia (N=385) | 0.0 percentage of participants |
| Olanzapine | Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase) | Parkinsonism (N=385) | 1.0 percentage of participants |
Secondary
Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase)
The MINI module C (MINI-C) is a rating scale for severity of suicidal thoughts and behaviors. The MINI-C is composed of 12 Yes/No questions with variable scores assigned to each question. The scale ranges from 0 to 52 with higher scores indicating a greater presence of suicidal thoughts and/or behaviors. Based upon scores, suicidality is defined as Low (1-8), Medium (9-16), and High (\>=17).
Time frame: Endpoint (Week 24)
Population: Total participants in the open-label extension phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase) | 1.3 percentage of participants |
Secondary
Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase)
In the MINI Major Depressive Episode module, participants are asked a series of Yes/No questions to determine whether or not they are experiencing a major depressive episode or a major depressive episode with melancholic features.
Time frame: Endpoint (Week 6)
Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase) | Major Depressive Episode | 55.5 percentage of participants |
| Olanzapine | Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase) | Major Depressive Episode with Melancholic Features | 77.8 percentage of participants |
| Placebo | Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase) | Major Depressive Episode | 60.4 percentage of participants |
| Placebo | Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase) | Major Depressive Episode with Melancholic Features | 74.1 percentage of participants |
p-value: 0.297Cochran-Mantel-Haenszel
p-value: 0.264Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase)
In the MINI Substance Dependence and Abuse Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current non-alcohol substance use dependence or abuse.
Time frame: Endpoint (Week 6)
Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase) | Dependence | 0.0 percentage of participants |
| Olanzapine | Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase) | Abuse | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase) | Dependence | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase) | Abuse | 0.0 percentage of participants |
Secondary
Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase)
In the MINI Psychotic Features Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing mood disorder with psychotic features or current psychotic disorders.
Time frame: Endpoint (Week 6)
Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase) | Mood Disorder with Psychotic Features | 3.6 percentage of participants |
| Olanzapine | Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase) | Psychotic Disorders | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase) | Mood Disorder with Psychotic Features | 2.4 percentage of participants |
| Placebo | Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase) | Psychotic Disorders | 0.6 percentage of participants |
p-value: 0.163Cochran-Mantel-Haenszel
p-value: 0.442Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Recovery (Acute Phase)
Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Baseline through Endpoint (Week 6 )
Population: Intention-to-treat (ITT) population; all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Recovery (Acute Phase) | 13.7 percentage of participants |
| Placebo | Percentage of Participants With Recovery (Acute Phase) | 9.4 percentage of participants |
p-value: 0.156Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Recovery (Open-Label Phase)
Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Population: Total participants in open-label extension phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Recovery (Open-Label Phase) | 69.9 percentage of participants |
Secondary
Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase)
Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Baseline through Endpoint (Week 6)
Population: Intention-to-treat (ITT) population; all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase) | 53.9 percentage of participants |
| Placebo | Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase) | 49.7 percentage of participants |
p-value: 0.367Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase)
Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Population: Total participants in open-label extension phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase) | 85.1 percentage of participants |
Secondary
Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase)
Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: Endpoint (Week 6)
Population: Intention-to-treat (ITT) population; all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase) | 52.5 percentage of participants |
| Placebo | Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase) | 43.3 percentage of participants |
p-value: 0.05Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase)
The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score.
Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Population: Total participants in the open-label extension phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase) | 43.7 percentage of participants |