Official Title: “Efficacy and Safety of Olanzapine in the Treatment of Patients With Bipolar I Disorder, Depressed: A Randomized, Double-Blind Comparison With Placebo”

The purpose of this study is to assess whether olanzapine is superior to placebo in patients with bipolar depression.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2010

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

Intervention(s) in this Clinical Trial

• Drug: Olanzapine
  • 5-20 mg, oral, once daily, for 24 weeks (pts randomized to olanzapine in SPII) or 18 weeks (pts randomized to placebo in SPII).
• Drug: Placebo
  • placebo tablets, oral, once daily at bedtime, 6 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • olanzapine, double-blind treatment
• Placebo Comparator: 2
  • Placebo, double-blind treatment
• Experimental: 3
  • Olanzapine, open label extension

Primary Measures

• Assess whether olanzapine is superior to placebo in patients with bipolar depression based on improvements in overall symptomatology, measured by the mean change in the Montgomery-Åsberg Depression Rating Scale total score.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No

Secondary Measures

• Assess olanzapine compared with placebo in terms of rate of response.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of remission of depression.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of improvement in clinical symptomatology, based on reductions from baseline in scores of the Clinical Global Impressions-Bipolar Version Severity of Illness scale.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of the rate of recovery, defined as a reduction in the Montgomery-Åsberg Depression Rating Scale total score for at least 4 weeks of treatment (post-baseline) and completion of the double-blind treatment.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of the improvement in clinical symptomology, based on the reductions of scores from baseline on the Young Mania Rating Scale.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of the improvement in clinical symptomatology, based on reductions from baseline in the Hamilton Depression Rating Scale-17 items scores.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms the presence of specific syndromic criteria, assessed by the Mini International Neuropsychiatric Interview major depressive episode (or major depressive episode with melancholic features) module.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of the presence of specific syndromic criteria, assessed by the Mini International Neuropsychiatric Interview manic episode module.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of the presence or absence of specific syndromic criteria, assessed by the Mini International Neuropsychiatric Interview psychotic disorders module.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in Mini International Neuropsychiatric Interview alcohol dependence/abuse module.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of the presence or absence of specific syndromic criteria, assessed by the Mini International Neuropsychiatric Interview substance dependence/abuse module.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: No
• Assess olanzapine compared with placebo in terms of the emergence of mania, defined as an increase in the Young Mania Rating Scale total score.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: Yes
• Assess olanzapine compared with placebo in terms of the incidence and severity of extrapyramidal symptoms as measured by the Drug-Induced Extrapyramidal Symptoms Scale.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: Yes
• Assess olanzapine compared with placebo in terms of safety as measured by treatment-emergent adverse events.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: Yes
• Assess olanzapine compared with placebo in terms of safety as measured by changes in vital signs.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: Yes
• Assess olanzapine compared with placebo in terms of safety as measured by changes in laboratory analytes.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: Yes
• Assess olanzapine compared with placebo in terms of safety as measured by changes in Electrocardiograms.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: Yes
• Assess olanzapine compared with placebo in terms of suicidality or serious suicide risk, as determined by an investigator's clinical judgement or increase on the suicidality module of the Mini International Neuropsychiatric Interview.
  • Time Frame: 10 weeks (includes screening period of 2-28 days)
    Safety Issue?: Yes
• Assess open-label olanzapine in terms of the rate of response with response defined as a reduction (from baseline to endpoint) of 50% or more in the Montgomery-Åsberg Depression Rating Scale total score.
  • Time Frame: 14 weeks (open-label extension period)
    Safety Issue?: No
• Assess open-label olanzapine in terms of the rate of remission of depression as defined as a score of less than or equal to 12 in the Montgomery-Åsberg Depression Rating Scale total score.
  • Time Frame: 14 weeks (open-label extension period)
    Safety Issue?: No
• Assess open-label olanzapine in terms of the rate of recovery as defined as a value of less than or equal to 12 in the Montgomery-Åsberg Depression Rating Scale total score for at least 4 weeks of treatment (post-baseline).
  • Time Frame: 14 weeks (open-label extension)
    Safety Issue?: No
• Assess open-label olanzapine in terms of the rate of improvement in clinical symptomatology, based on reductions of Young Mania Rating Scale scale scores from baseline.
  • Time Frame: 14 weeks (open-label extension)
    Safety Issue?: No
• Assess open-label olanzapine in terms of the rate of emergence of mania, defined as a Young Mania Rating Scale total score greater than or equal to 15.
  • Time Frame: 14 weeks (open-label extension)
    Safety Issue?: Yes
• Assess open-label olanzapine in terms of the rate of the incidence and severity of extra-pyramidal symptoms as measured by the Drug-Induced Extrapyramidal Symptoms Scale.
  • Time Frame: 14 weeks (open-label extension)
    Safety Issue?: Yes
• Assess open-label olanzapine in terms of safety, as measured by Treatment Emergent Adverse Events.
  • Time Frame: 14 weeks (open-label extension)
    Safety Issue?: Yes
• Assess open-label olanzapine in terms of safety, as measured by change in vital signs.
  • Time Frame: 14 weeks (open-label extension)
    Safety Issue?: Yes
• Assess open-label olanzapine in terms of safety as measured by electrocardiograms.
  • Time Frame: 14 weeks (open-label extension)
    Safety Issue?: Yes
• Assess open-label olanzapine in terms of suicidality rate or serious suicide risk, determined by an investigator's clinical judgement or by a score greater than or equal to 17 on the Mini International Neuropsychiatric Interview suicidality module.
  • Time Frame: 14 weeks (open-label extension)
    Safety Issue?: Yes

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 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, at study entry
• Patients must have a current HAMD-17 score greater than or equal to 18 at V1 and V2
• Patients must have a current YMRS total score less than or equal to 8 at V2.

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

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 was prescribed at an appropriate dose and duration

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 64 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eli Lilly and Company

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5hrs, EST) Study Director Eli Lilly and Company  

Overall Contact: There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00510146

Study ID Number: 11218

ClinicalTrials.gov Identifier: NCT00510146

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry