Clinical trial NCT00510146: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depression, Bipolar
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2007-08-01
Enrollment: 514
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
Secondary outcomes:
measure: Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase)
timeFrame: Endpoint (Week 6)
measure: Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase)
timeFrame: Baseline through Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Percentage of Participants With Recovery (Acute Phase)
timeFrame: Baseline through Endpoint (Week 6 )
measure: Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase)
timeFrame: Endpoint (Week 6)
measure: Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase)
timeFrame: Endpoint (Week 6)
measure: Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase)
timeFrame: Endpoint (Week 6)
measure: Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)
timeFrame: Endpoint (Week 6)
measure: Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase)
timeFrame: Endpoint (Week 6)
measure: Percentage of Participants With Emergence of Mania During the Study (Acute Phase)
timeFrame: Baseline through Endpoint (Week 6)
measure: Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)
timeFrame: Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Weight (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Albumin (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: 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)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Hematocrit (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Hemoglobin (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Prolactin (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in Heart Rate (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)
timeFrame: Baseline, Endpoint (Week 6)
measure: Number of Participants With Adverse Events (Acute Phase)
timeFrame: Baseline through Week 6 (Acute Phase)
measure: Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
measure: Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
measure: Percentage of Participants With Recovery (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
measure: Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)
timeFrame: Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Weight (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Chloride (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Creatinine (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Platelet Count (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Prolactin (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Uric Acid (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in ECG (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Change From Baseline to Endpoint in Heart Rate (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
measure: Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase)
timeFrame: Endpoint (Week 24)
measure: Number of Participants With Adverse Events (Open-Label Phase)
timeFrame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Other outcomes:
Locations:
city: Beijing
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Changsha
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Chengdu
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Guang Zhou
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Hangzhou
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Harbin
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Kunming
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Nanjing
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Shanghai
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Wu Han
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Xi'An
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Hiroshima
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Shiga
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Tokyo
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Seongnam-Si
country: Korea, Republic of
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Seoul
country: Korea, Republic of
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Katagiri H, Tohen M, McDonnell DP, Fujikoshi S, Case M, Kanba S, Takahashi M, Gomez JC. Safety and efficacy of olanzapine in the long-term treatment of Japanese patients with bipolar I disorder, depression: an integrated analysis. Psychiatry Clin Neurosci. 2014 Jul;68(7):498-505. doi: 10.1111/pcn.12156. Epub 2014 Mar 4.
citation: Katagiri H, Tohen M, McDonnell DP, Fujikoshi S, Case M, Kanba S, Takahashi M, Gomez JC. Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Japanese subpopulation analysis of a randomized, double-blind, placebo-controlled study. BMC Psychiatry. 2013 May 14;13:138. doi: 10.1186/1471-244X-13-138.
citation: Tohen M, McDonnell DP, Case M, Kanba S, Ha K, Fang YR, Katagiri H, Gomez JC. Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression. Br J Psychiatry. 2012 Nov;201(5):376-82. doi: 10.1192/bjp.bp.112.108357. Epub 2012 Aug 23.