Olanzapine Treatment of Patients With Bipolar I Disorder

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.

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 (participants randomized to olanzapine in double-blind treatment period) or 18 weeks (participants randomized to placebo in double-blind treatment period).
• Drug: Placebo
  • placebo tablets, oral, once daily at bedtime, 6 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Olanzapine
  • During double-blind treatment, participants receive olanzapine at a dose of 5 milligram (mg) which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
• Placebo Comparator: Placebo
  • Matching placebo administered once daily, by mouth during double-blind treatment.
• Experimental: Olanzapine (open-label treatment period)
  • During open-label treatment, participants randomized to placebo in double-blind period will receive olanzapine 5 mg starting at Week 6. Participants randomized to olanzapine must be at a 5 mg olanzapine dose at Week 7. Those on higher doses will be reduced between Week 6 and Week 7 (10 mg reduced to 5 mg; 15 mg reduced to 10 mg and then to 5 mg at Week 7; 20 mg reduced to 15 mg and then 10 mg to dosing at 5 mg at Week 7). Dose increases beyond Week 7 are permitted and at the investigator's discretion.

Primary Measures

• Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: No

Secondary Measures

• Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase)
  • Time Frame: Endpoint (Week 6)
    Safety Issue?: No
• Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase)
  • Time Frame: Baseline through Endpoint (Week 6)
    Safety Issue?: No
• Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: No
• Percentage of Participants With Recovery (Acute Phase)
  • Time Frame: Baseline through Endpoint (Week 6 )
    Safety Issue?: No
• Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: No
• Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: No
• Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase)
  • Time Frame: Endpoint (Week 6)
    Safety Issue?: No
• Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase)
  • Time Frame: Endpoint (Week 6)
    Safety Issue?: No
• Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase)
  • Time Frame: Endpoint (Week 6)
    Safety Issue?: No
• Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)
  • Time Frame: Endpoint (Week 6)
    Safety Issue?: No
• Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase)
  • Time Frame: Endpoint (Week 6)
    Safety Issue?: No
• Percentage of Participants With Emergence of Mania During the Study (Acute Phase)
  • Time Frame: Baseline through Endpoint (Week 6)
    Safety Issue?: Yes
• Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)
  • Time Frame: Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Weight (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Albumin (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Hematocrit (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Hemoglobin (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Prolactin (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Heart Rate (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)
  • Time Frame: Baseline, Endpoint (Week 6)
    Safety Issue?: Yes
• Number of Participants With Adverse Events (Acute Phase)
  • Time Frame: Baseline through Week 6 (Acute Phase)
    Safety Issue?: Yes
• Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
    Safety Issue?: No
• Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
    Safety Issue?: No
• Percentage of Participants With Recovery (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
    Safety Issue?: No
• Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: No
• Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
    Safety Issue?: Yes
• Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)
  • Time Frame: Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Weight (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Chloride (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Creatinine (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Platelet Count (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Prolactin (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Uric Acid (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in ECG (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Change From Baseline to Endpoint in Heart Rate (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
    Safety Issue?: Yes
• Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase)
  • Time Frame: Endpoint (Week 24)
    Safety Issue?: Yes
• Number of Participants With Adverse Events (Open-Label Phase)
  • Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
    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 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (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 International Neuropsychiatric Interview (MINI), at study entry
• Patients must have a current 17-item Hamilton Depression Rating Scale (HAMD-17) score greater than or equal to 18 at Visit 1 and Visit 2
• Patients must have a current Young Mania Rating Scale (YMRS) total score less than or equal to 8 at Visit 2.

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 selective serotonin reuptake inhibitor (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 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 Investigator: Eli Lilly and Company Industry

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  

Information obtained from ClinicalTrials.gov on February 08, 2012

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