A Comparison of Olanzapine in Combination With a Mood Stabilizer vs Mood Stabilizer Alone, in Mixed Bipolar Patients

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Double-Blind Placebo Controlled Trial of Divalproex and Olanzapine in Bipolar I Disorder, Mixed Episode

Conditions
-----------------
Bipolar I Disorder

Intervention / Treatment
-----------------
* Drug: olanzapine
* Drug: placebo
* Drug: divalproex


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with a mixed episode of bipolar I disorder. Have had at least one previous manic or mixed episode associated with bipolar disorder You must be between 18 and 60 years old. You must be able to visit the doctor's office three times in the first week and then once every week for the next five weeks. If you are a female, you must have a negative pregnancy test and be using an effective method of contraception. Exclusion Criteria: You have a diagnosis of schizophrenia, schizoaffective disorder or substance abuse or dependence. You have diseases of the intestinal tract, lungs, liver, kidney, nervous or endocrine systems, or blood. Have required a recent thyroid hormone supplement to treat hypothyroidism (must have been on a stable dose of the medication for at least 2 months prior to Visit 3). You are allergic to any of the medications involved in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>olanzapine and divalproex | Drug: olanzapine<br>* 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).<br>* Other names: Zyprexa;Drug: divalproex<br>* 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).<br>|
| Placebo Comparator: 2<br>placebo and divalproex | Drug: placebo<br>* placebo, capsules, by mouth every evening, daily, for 6 weeks.<br>Drug: divalproex<br>* 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).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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) | 

Secondary Outcome Measures

| Outcome Measure | 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) | 
| 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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mixed episode associated with Bipolar I