Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| F1D-US-HGMO |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Whether treatment with olanzapine in combination with mood stabilizer reduces symptoms of both mania and depression more than treatment with mood stabilizer alone, in patients with a mixed episode of bipolar I disorder.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | olanzapine and divalproex |
|
| 2 | Placebo Comparator | placebo and divalproex |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| olanzapine | Drug | 15mg, capsules, by mouth every evening, daily for minimum of one day, followed by 5-20mg, capsules, by mouth every evening, daily for remainder of study (6 weeks total). |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in Young Mania Rating Scale (YMRS) Scores From Baseline to Endpoint. | 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. | Baseline to endpoint (6 weeks) |
| Mean Change in Hamilton Depression Rating Scale-21 (HAMD) Scores From Baseline to Endpoint. | The 21-item HAMD measures depression severity. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 60. | Baseline to endpoint (6 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Meeting the Criteria for Mixed Onset of Action | The original outcome measure was Time to Mixed Onset of Action (at least a 25% reduction on HAMD and YMRS total scores from baseline); however since upper limit of measure of dispersion could not be computed by observed data, which is not allowed on this system, number of patients with event are presented instead. | Baseline to endpoint (6 weeks) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hialeah | Florida | 33016 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21044339 | Derived | Houston JP, Gatz JL, Degenhardt EK, Jamal HH. Symptoms predicting remission after divalproex augmentation with olanzapine in partially nonresponsive patients experiencing mixed bipolar I episode: a post-hoc analysis of a randomized controlled study. BMC Res Notes. 2010 Nov 2;3:276. doi: 10.1186/1756-0500-3-276. | |
| 19778495 | Derived |
Not provided
Not provided
Study Period 1 was a 2-28 day day period allowing for screening, divalproex treatment initiation (if appropriate) and washout. Patients meeting diagnostic criteria and having therapeutic serum levels of divalproex in target range of 75 to 125 µg/mL (≥80 µg/mL recommended) during Study Period I, will be randomized into either placebo or olanzapine.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Olanzapine | Olanzapine: 15mg, capsules, by mouth every evening, daily for minimum of one day, followed by 5-20mg, capsules, by mouth every evening, daily for remainder of study (6 weeks total). Divalproex: dose to maintain blood levels of 75-125 ug/mL, by mouth, twice a day, daily for 6 weeks (following dose achieved in Study Period I). |
| FG001 | Placebo | Placebo: placebo capsules, by mouth every evening, daily, for 6 weeks. Divalproex: dose to maintain blood levels of 75-125 ug/mL, by mouth, twice a day, daily for 6 weeks (following dose achieved in Study Period I). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Olanzapine | Olanzapine: 15mg, capsules, by mouth every evening, daily for minimum of one day, followed by 5-20mg, capsules, by mouth every evening, daily for remainder of study (6 weeks total). Divalproex: dose to maintain blood levels of 75-125 ug/mL, by mouth, twice a day, daily for 6 weeks (following dose achieved in Study Period I). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change in Young Mania Rating Scale (YMRS) Scores From Baseline to Endpoint. | 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. | Intent to Treat analysis. All randomized patients with baseline & at least one post-baseline measure. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to endpoint (6 weeks) |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Olanzapine | Olanzapine: 15mg, capsules, PO at Q HS, daily for 1 week followed by 5-20mg, capsules, PO at Q HS daily for 5 weeks (6 weeks total). Divalproex: dose to maintain blood levels of 75-125 ug/mL, PO, BID, daily for 6 weeks (following d ose achieved in Study Period I) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | MedDRA11.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA11.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 1-800-545-5979 |
| ID | Term |
|---|---|
| D000077152 | Olanzapine |
| D014635 | Valproic Acid |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| placebo | Drug | placebo, capsules, by mouth every evening, daily, for 6 weeks. |
|
| divalproex | Drug | dose to maintain blood levels of 75-125 ug/mL, by mouth, twice a day, daily for 52 days (Study Period I and Study Period II). |
|
| Number of Participants Meeting the Criteria for Mixed Response | The original outcome measure was Time to Mixed Response(at least a 50% reduction on HAMD and YMRS total scores from baseline); however since upper limit of measure of dispersion could not be computed by observed data, which is not allowed on this system, number of patients with event are presented instead. | baseline to endpoint (6 weeks) |
| Mean Change in Clinical Global Impression for Bipolar Illness Severity (CGI-BP) From Baseline to Endpoint | CGI-BP Severity is used by the clinician to record the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Baseline to endpoint (6 weeks) |
| Number of Patients Hospitalized Due to Relapse of Mania or Depression. | Number of participants hospitalized as a result of relapse of mania or depression. | Baseline to endpoint (6 weeks) |
| Clinically Significant Laboratory Values - Fasting Cholesterol Change From Baseline | Change from Baseline to endpoint in cholesterol: value of cholesterol measure at endpoint minus the value at baseline. | Baseline to endpoint (6 weeks) |
| Clinically Significant Laboratory Values - Fasting Triglycerides Change From Baseline | Change from baseline to endpoint in triglycerides: Value of triglyceride measure at endpoint minus value at baseline. | Baseline to endpoint (6 weeks) |
| Clinically Significant Laboratory Values - Fasting Blood Glucose Change From Baseline | Change from baseline to endpoint in fasting blood glucose: Value of fasting blood glucose measure at endpoint minus value at baseline. | Baseline to endpoint (6 weeks) |
| Clinically Significant Laboratory Values - Bilirubin Total Change From Baseline | Change from baseline to endpoint in bilirubin total: Value of bilirubin total measure at endpoint minus value at baseline. | Baseline to endpoint (6 weeks) |
| Clinically Significant Vital Signs - Body Mass Index Change From Baseline | Change from baseline to endpoint in body mass index (an estimate of body fat derived by dividing body weight by height squared): Value of body mass index measure at endpoint minus value at baseline. | Baseline to endpoint (6 weeks) |
| Clinically Significant Vital Signs - Weight Change From Baseline | Change from baseline to endpoint: Value of weight measure at endpoint minus value at baseline. | Baseline to endpoint (6 weeks) |
| Clinically Significant Vital Signs - Percentage of Participants With Baseline-to-Endpoint Weight Increase of at Least Seven Percent (7%) | Percentages of participants in each group who experienced an increase in weight of at least 7% from baseline to endpoint. | Baseline to endpoint (6 weeks) |
| United States |
| Houston JP, Tohen M, Degenhardt EK, Jamal HH, Liu LL, Ketter TA. Olanzapine-divalproex combination versus divalproex monotherapy in the treatment of bipolar mixed episodes: a double-blind, placebo-controlled study. J Clin Psychiatry. 2009 Nov;70(11):1540-7. doi: 10.4088/JCP.08m04895yel. Epub 2009 Sep 22. |
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Physician Decision |
|
| Sponsor Decision |
|
| Lack of Efficacy |
|
| Adverse Event |
|
| Death |
|
| BG001 |
| Placebo |
Placebo: placebo capsules, by mouth every evening, daily, for 6 weeks. Divalproex: dose to maintain blood levels of 75-125 ug/mL, by mouth, twice a day, daily for 6 weeks (following dose achieved in Study Period I). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Race/Ethnicity | Number | participants |
|
| Body Mass Index (BMI) | Body mass index is an estimate of body fat based on body weight divided by height squared. | Mean | Standard Deviation | kilograms per square meters |
|
| Body Weight | Mean | Standard Deviation | kilograms |
|
| OG001 | Placebo | Placebo: placebo capsules, by mouth every evening, daily, for 6 weeks. Divalproex: dose to maintain blood levels of 75-125 ug/mL, by mouth, twice a day, daily for 6 weeks (following dose achieved in Study Period I). |
|
|
|
| Primary | Mean Change in Hamilton Depression Rating Scale-21 (HAMD) Scores From Baseline to Endpoint. | The 21-item HAMD measures depression severity. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 60. | Intent to Treat analysis. All randomized patients with baseline & at least one post-baseline measure. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Number of Participants Meeting the Criteria for Mixed Onset of Action | The original outcome measure was Time to Mixed Onset of Action (at least a 25% reduction on HAMD and YMRS total scores from baseline); however since upper limit of measure of dispersion could not be computed by observed data, which is not allowed on this system, number of patients with event are presented instead. | All randomized participants with both baseline and post-baseline measures. Intention to Treat analysis. | Posted | Number | participants | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Number of Participants Meeting the Criteria for Mixed Response | The original outcome measure was Time to Mixed Response(at least a 50% reduction on HAMD and YMRS total scores from baseline); however since upper limit of measure of dispersion could not be computed by observed data, which is not allowed on this system, number of patients with event are presented instead. | All randomized participants with both baseline and post-baseline measures. Intention to Treat analysis. | Posted | Number | participants | baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Mean Change in Clinical Global Impression for Bipolar Illness Severity (CGI-BP) From Baseline to Endpoint | CGI-BP Severity is used by the clinician to record the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Intent to Treat analysis. Number of randomized patients with baseline and at least one nonmissing postbaseline value. Last observation carried forward. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Number of Patients Hospitalized Due to Relapse of Mania or Depression. | Number of participants hospitalized as a result of relapse of mania or depression. | Intent to Treat analysis. All randomized patients. | Posted | Number | participants | Baseline to endpoint (6 weeks) |
|
|
|
| Secondary | Clinically Significant Laboratory Values - Fasting Cholesterol Change From Baseline | Change from Baseline to endpoint in cholesterol: value of cholesterol measure at endpoint minus the value at baseline. | All randomized participants with both baseline and at least one post-baseline measure. Intention to Treat analysis. | Posted | Mean | Standard Deviation | milligrams per deciliter | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Clinically Significant Laboratory Values - Fasting Triglycerides Change From Baseline | Change from baseline to endpoint in triglycerides: Value of triglyceride measure at endpoint minus value at baseline. | All randomized participants with both baseline and post-baseline measures. Intention to Treat analysis. | Posted | Mean | Standard Deviation | milligrams per deciliter | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Clinically Significant Laboratory Values - Fasting Blood Glucose Change From Baseline | Change from baseline to endpoint in fasting blood glucose: Value of fasting blood glucose measure at endpoint minus value at baseline. | All randomized participants with both baseline and post-baseline measures. Intention to Treat analysis. | Posted | Mean | Standard Deviation | milligrams per deciliter | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Clinically Significant Laboratory Values - Bilirubin Total Change From Baseline | Change from baseline to endpoint in bilirubin total: Value of bilirubin total measure at endpoint minus value at baseline. | All randomized participants with both baseline and post-baseline measures. Intention to Treat analysis. | Posted | Mean | Standard Deviation | micromoles per Liter | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Clinically Significant Vital Signs - Body Mass Index Change From Baseline | Change from baseline to endpoint in body mass index (an estimate of body fat derived by dividing body weight by height squared): Value of body mass index measure at endpoint minus value at baseline. | All randomized participants with both baseline and post-baseline measures. Intention to Treat analysis. | Posted | Least Squares Mean | Standard Error | kilograms per square meters | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Clinically Significant Vital Signs - Weight Change From Baseline | Change from baseline to endpoint: Value of weight measure at endpoint minus value at baseline. | All randomized participants with both baseline and post-baseline measures. Intention to Treat analysis. | Posted | Least Squares Mean | Standard Error | kilograms | Baseline to endpoint (6 weeks) |
|
|
|
|
| Secondary | Clinically Significant Vital Signs - Percentage of Participants With Baseline-to-Endpoint Weight Increase of at Least Seven Percent (7%) | Percentages of participants in each group who experienced an increase in weight of at least 7% from baseline to endpoint. | All randomized participants with both baseline and post-baseline measures. Intention to Treat analysis. | Posted | Number | percentage of participants | Baseline to endpoint (6 weeks) |
|
|
|
|
| 3 |
| 80 |
| EG001 | Placebo | Placebo: placebo capsules, PO, at Q HS, daily, for 6 weeks. Divalproex: dose to maintain blood levels of 75-125 ug/mL, PO, BID, daily for 6 weeks (following dose achieved in Study Period I). | 5 | 63 |
| Chest pain | General disorders | MedDRA11.0 | Systematic Assessment |
|
| Death | General disorders | MedDRA11.0 | Systematic Assessment |
|
| Acute hepatic failure | Hepatobiliary disorders | MedDRA11.0 | Systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA11.0 | Systematic Assessment |
|
| Overdose | Injury, poisoning and procedural complications | MedDRA11.0 | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA11.0 | Systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA11.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA11.0 | Systematic Assessment |
|
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA11.0 | Systematic Assessment |
|
| Bipolar I disorder | Psychiatric disorders | MedDRA11.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA11.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA11.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA11.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA11.0 | Systematic Assessment |
|
| Stomach discomfort | Gastrointestinal disorders | MedDRA11.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA11.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA11.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA11.0 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA11.0 | Systematic Assessment |
|
| Increased appetite | Metabolism and nutrition disorders | MedDRA11.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA11.0 | Systematic Assessment |
|
| Akathisia | Nervous system disorders | MedDRA11.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA11.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA11.0 | Systematic Assessment |
|
| Sedation | Nervous system disorders | MedDRA11.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA11.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA11.0 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA11.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA11.0 | Systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA11.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA11.0 | Systematic Assessment |
|
Not provided
| D006571 | Heterocyclic Compounds |
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| Low Density Lipoprotein Baseline (N=62,N=64) |
|
| Low Density Lipoprotein Change (N=62,N=64) |
|
| High Density Lipoprotein Baseline |
|
| High Density Lipoprotein Change from Baseline |
|
Type III sums of squares of ANOVA model: Ranked Change= Treatment + Pooled Investigator |
| 0.924 |
P-value for Low Density Lipoprotein Change from Baseline |
| 95 |
| No |
| Superiority or Other |
| ANOVA | Type III sums of squares of ANOVA model: Ranked Change= Treatment + Pooled Investigator | 0.122 | P-value for High Density Lipoprotein Change from Baseline | 95 | No | Superiority or Other |