Trial of Olanzapine in Patients With Manic or Mixed Episode of Bipolar I Disorder

Study Overview
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Brief Summary
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The purpose of this study is to confirm the efficacy of olanzapine in the treatment of manic or mixed symptoms associated with bipolar I disorder.

Official Title
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Placebo- and Haloperidol-Controlled Double-Blind Trial of Olanzapine in Patients With Manic or Mixed Episode of Bipolar I Disorder

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: olanzapine
* Drug: haloperidol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the criteria for manic or mixed episodes according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) and have a diagnosis of 294.4x Bipolar I Disorder, Most Recent Episode Manic or 296.6x Bipolar I Disorder, Most Recent Episode Mixed. Have a total score on the Young Mania Rating Scale (YMRS) of at least 20 at Visit 1 and Visit 2. Exclusion Criteria: Have received an antidepressant or a psychostimulant within 5 days prior to Visit 1. The duration of the current episode is more than 90 days at Visit 1. Have a history or a diagnosis of diabetes mellitus. Have received any psychotropic medication within 2 days prior to Visit 2 (except for benzodiazepines).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine<br>olanzapine: 5 to 20 mg per day for 6 weeks | Drug: olanzapine<br>* 5-20 mg, oral, once daily (evening), for 6 weeks<br>* Other names: Zyprexa;|
| Active Comparator: Haloperidol<br>haloperidol: 2.5 to 10 mg per day for 6 weeks | Drug: haloperidol<br>* 2.5-10 mg, oral, twice daily (morning and evening), for 6 weeks.<br>|
| Placebo Comparator: Placebo<br>placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks | Drug: placebo<br>* placebo, oral tablets, twice daily (morning and evening), for 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score | 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, 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) | 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, 6 weeks | 
| Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol) | Remission of bipolar disorder was defined as completing the 6-week period with meeting the criteria for Young Mania Rating Scale (YMRS) total score of 12 or less and 17-Item Hamilton Depression Rating Scale (HAMD-17) total scores of 7 or less at Week 6. YMRS is an 11-item scale measuring severity of manic episodes; total score ranges = 0 (normal) to 60 (severe). The 17-item HAMD measures depression severity; total score ranges = 0 (normal) to 52 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100. | 6 weeks | 
| Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness | A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of overall mood symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Baseline, 6 weeks | 
| Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale | A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of manic symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Baseline, 3 weeks, 6 weeks | 
| Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks | Participants who had 50 percent or more decrease from the baseline in YMRS total scores were defined as a responder. 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. Response Rate (percent) = number of patients meeting response criterion for manic symptom divided by number of patients in treatment arm, multiplied by 100. | Baseline, 3 weeks, 6 weeks | 
| Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks | Participants who had a YMRS total score of 12 or less were considered to be in remission of manic symptoms. YMRS is an 11-item scale that measures severity of manic episodes; total score ranges from 0 (normal) to 60 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100. | 3 weeks, 6 weeks | 
| Percentage of Participants Who Switched to Symptomatic Depression | Switch to symptomatic depression was defined as HAMD-17 total score ≥13 at any time in the participants with HAMD-17 total scores ≤7 at baseline. 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). | 3 weeks, 6 weeks | 
| Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) | Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total Positive Subscale scores range from 7 to 49. For this study, the score was converted to 0 to 6 for each item range; hence, the total positive subscale score ranges from 0 to 42. | Baseline, 3 weeks, 6 weeks | 
| Percentage of Participants Who Switched to Syndromic Depression | Switch to syndromic depression was operationally defined by meeting both of the following criteria: At baseline, the symptoms did not meet the criteria for a mixed episode based on the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). The critiera were met for a Major Depressive Episode (MDE), at any point after randomization, based on DSM-IV-TR. Rather than the 2-week period required for an MDE in the DSM-IV-TR, the patient had to meet the criteria of an MDE for at least 7 consecutive days (during Weeks 1 through 6). | 3 weeks, 6 weeks | 
| Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score | Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the sum of the 8 item scores, for a total range of 0 (normal) to 32 (severe). | Baseline to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Manic or mixed episode associated with bipolar I disorder