Safety and Efficacy of Olanzapine in the Long-term Treatment for Bipolar I Disorder, Depressed

Study Overview
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Brief Summary
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To assess the efficacy and safety of olanzapine in the long-term treatment for patients with bipolar I disorder, depressed.

Detailed Description
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This is an open-label, multi-center, long-term treatment study conducted only in Japanese sites. The subjects are patients who fulfill the diagnostic criteria for bipolar I disorder, most recent episode depressed, as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) (296.50=unspecified, 296.52=moderate severity, 296.53=severe without psychotic features, 296.54=severe with psychotic features), who have completed Study HGMP (NCT#00510146) and patients who did not participate in Study HGMP who have been recruited to participate in Study HGMS.

Official Title
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Safety and Efficacy of Olanzapine (LY170053) in the Long-term Treatment for Patients With Bipolar I Disorder, Depressed

Conditions
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Bipolar I Disorder

Intervention / Treatment
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* Drug: Olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be aged 18 to less than 75 years. 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. 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. Male patients who are not surgically sterilized must agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. Patients must fulfill the diagnostic criteria for bipolar I disorder, most recent episode depressed, as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Patients must have experienced, in the opinion of the investigator, at least one previous manic or mixed episode, as defined in the DSM-IV-TR. Patients must have a current Young Mania Rating Scale (YMRS) Total score =<8. Exclusion Criteria: Is investigator site personnel directly affiliated with this study or their immediate families. Is a Lilly employee. Has previously completed or withdrawn from this study or any other study investigating olanzapine. Is pregnant or nursing. Has a serious, unstable illness such that death is anticipated within 1 year or intensive care unit hospitalization for the disease is anticipated within 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-Olanzapine<br>Participants who received olanzapine 5-20 mg/day in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks. | Drug: Olanzapine<br>* 5-20 mg/day, oral, daily<br>* Other names: LY170053;|
| Experimental: Pre-Placebo<br>Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks. | Drug: Olanzapine<br>* 5-20 mg/day, oral, daily<br>* Other names: LY170053;|
| Experimental: New Olanzapine<br>Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks. | Drug: Olanzapine<br>* 5-20 mg/day, oral, daily<br>* Other names: LY170053;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events Leading to Discontinuation | An adverse event (AE) is an untoward medical event associated with the use of the study drug or study procedure, whether or not it is considered related to the study drug or study procedure. Results presented are the percentage of participants who experienced an adverse event that resulted in the discontinuation of the study. | Baseline through 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glucose and Lipid Panel at Week 24 or Week 48 Endpoint |  | baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Change From Baseline in Weight at Week 24 or Week 48 Endpoint |  | baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 24 or Week 48 Endpoint | 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). | baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 24 or Week 48 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, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Change From Baseline in Clinical Global Improvement- Bipolar (CGI-BP) at Week 24 or Week 48 Endpoint | CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The scores for mania, depression, and overall illness each range from 1 (normal, not ill) to 7 (very seriously ill). | baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Percentage of Participants With Emergence of Mania at Week 24 or Week 48 | 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. | 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Percentage of Participants With High Suicidality at Week 24 or Week 48 | 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). | 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Week 24 or Week 48 | EPS symptoms measured by DIEPSS are grouped into 4 categories: Parkinsonism, akathisia, dystonia, and dyskinesia. Severity ranges from level 0 (none, normal) to 4 (severe). A participant is deemed to have EPS at endpoint if they have an abnormal endpoint. Normal baseline Parkinsonism is defined as a score not ≥3 on 1 item or ≥2 on 2 items; abnormal endpoint is a score ≥3 on 1 item or ≥2 on 2 items, or an increase of 3 on Parkinsonism total. Normal 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. | 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Change From Baseline in Hemoglobin (HbA1c) at Week 24 or Week 48 Endpoint | HbA1c is a test that measures the amount of glycated hemoglobin in the blood over prolonged periods of time. | baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Change From Baseline in Prolactin at Week 24 or Week 48 Endpoint |  | baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 
| Change From Baseline to in QTcF at Week 24 or Week 48 Endpoint | Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval) | baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar