Depression, BipolarPhase 3NCT00510146
Olanzapine Treatment of Patients With Bipolar I Disorder
A Phase 3 study testing Olanzapine in people with Depression, Bipolar, run by Eli Lilly and Company at 16 sites in 3 countries.
Trial summary
The purpose of this study is to assess whether olanzapine is superior to placebo in patients with bipolar depression. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Depression, Bipolar
- What is being tested?
- Olanzapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 514 participants
- Where
- 16 sitesin 3 countries
- Study dates
- Aug 2007to Jul 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
China11 sites
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.
Beijing, 100088
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Changsha, 410008
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Chengdu, 610041
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Guangzhou, 510370
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Hangzhou, 310003
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Harbin, 150001
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Kunming, 650032
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Nanjing, 210029
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Shanghai, 200030
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Wuhan, 430060
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Xi'an, 710032
Japan3 sites
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.
Hiroshima, 731-0501
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.
Shiga, 525-0037
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.
Tokyo, 170-0002
South Korea2 sites
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.
Seongnam-si, 463-707
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.
Seoul, 110-744
About this study
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.
Read the detailed description
- Dose range and administration mode: Oral Olanzapine 5mg - 20mg/day
- Duration:
- Screening phase is 2-28 days.
- Double-blind treatment phase is 6 weeks
- Open-label extension phase is 18 weeks
- Conditions
- Depression, Bipolar
- Being tested
- Olanzapine, Placebo
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlanzapineDrug
Also called LY170053, Zyprexa
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).
PlaceboDrug
placebo tablets, oral, once daily at bedtime, 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Olanzapine | Experimental | 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. Receives: Drug: Olanzapine |
| Placebo | Placebo comparator | Matching placebo administered once daily, by mouth during double-blind treatment. Receives: Drug: Placebo |
| Olanzapine (open-label treatment period) | Experimental | 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. Receives: Drug: Olanzapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)
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).
Measured: Baseline, Endpoint (Week 6)
Secondary outcomes (51)
Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase)
Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score. 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).
Measured: Endpoint (Week 6)
Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase)
Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. 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).
Measured: Baseline through Endpoint (Week 6)
Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The score ranges from 1 (normal, not ill) to 7 (very seriously ill).
Measured: Baseline, Endpoint (Week 6)
Percentage of Participants With Recovery (Acute Phase)
Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. 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).
Measured: Baseline through Endpoint (Week 6 )
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (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.
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)
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).
Measured: Baseline, Endpoint (Week 6)
Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase)
In the MINI Major Depressive Episode module, participants are asked a series of Yes/No questions to determine whether or not they are experiencing a major depressive episode or a major depressive episode with melancholic features.
Measured: Endpoint (Week 6)
Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase)
In the MINI Manic Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing hypomanic or manic episodes.
Measured: Endpoint (Week 6)
Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase)
In the MINI Psychotic Features Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing mood disorder with psychotic features or current psychotic disorders.
Measured: Endpoint (Week 6)
Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)
In the MINI Alcohol Abuse and Dependence Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current alcohol dependence or abuse.
Measured: Endpoint (Week 6)
Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase)
In the MINI Substance Dependence and Abuse Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current non-alcohol substance use dependence or abuse.
Measured: Endpoint (Week 6)
Percentage of Participants With Emergence of Mania During the Study (Acute Phase)
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.
Measured: Baseline through Endpoint (Week 6)
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)
EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not >=3 on 1 item nor >=2 on 2 items; abnormal endpoint is defined as a score >=3 on 1 item or >=2 on 2 items, or an increase of 3 on Parkinsonism total. 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.
Measured: Endpoint (Week 6)
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Weight (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Albumin (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
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)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Hematocrit (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Hemoglobin (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Prolactin (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval).
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Heart Rate (Acute Phase)
Measured: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)
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.
Measured: Baseline, Endpoint (Week 6)
Number of Participants With Adverse Events (Acute Phase)
Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events.
Measured: Baseline through Week 6 (Acute Phase)
Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase)
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). Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score.
Measured: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase)
Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. 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).
Measured: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Percentage of Participants With Recovery (Open-Label Phase)
Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. 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).
Measured: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label 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.
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase)
Emergence of mania is defined as first occurrence of score of >=15 in the YMRS total score in the Open-Label Extension. 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.
Measured: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)
EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not >=3 on 1 item nor >=2 on 2 items; abnormal endpoint is defined as a score >=3 on 1 item or >=2 on 2 items, or an increase of 3 on Parkinsonism total. 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.
Measured: Endpoint (Week 24)
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Weight (Open-Label Phase)
Measured: Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Chloride (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Creatinine (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Platelet Count (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Prolactin (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Uric Acid (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in ECG (Open-Label Phase)
Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval).
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Heart Rate (Open-Label Phase)
Measured: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase)
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).
Measured: Endpoint (Week 24)
Number of Participants With Adverse Events (Open-Label Phase)
Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events.
Measured: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionMar 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Depression, BipolarStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 514 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00510146
- Sponsor's protocol ID
- 11218
- Other IDs
- F1D-MC-HGMP
- Status last verified
- Apr 2011
- First submitted
- 30 Jul 2007
- Last updated
- 26 May 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24417745Katagiri 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.
PubMed 23672672Tohen 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.
PubMed 22918966
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Olanzapine in the Treatment of Patients With Bipolar I Disorder, Depressed: A Randomized, Double-Blind Comparison With Placebo
- ClinicalTrials.gov ID
- NCT00510146
- Acronym / sponsor ID
- 11218
- Conditions
- Depression, Bipolar
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 514 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- Mar 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 1 Aug 2007 (estimated)
- Results
- Posted 26 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess whether olanzapine is superior to placebo in patients with bipolar depression.
Detailed description
- Dose range and administration mode: Oral Olanzapine 5mg - 20mg/day
- Duration:
- Screening phase is 2-28 days.
- Double-blind treatment phase is 6 weeks
- Open-label extension phase is 18 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Olanzapine | Experimental | Drug: OlanzapineDuring 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 | Placebo comparator | Drug: PlaceboMatching placebo administered once daily, by mouth during double-blind treatment. |
| Olanzapine (open-label treatment period) | Experimental | Drug: OlanzapineDuring 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. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlanzapineAlso: LY170053, Zyprexa5-20 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 | Olanzapine, Olanzapine (open-label treatment period) |
| Placeboplacebo tablets, oral, once daily at bedtime, 6 weeks | Drug | Placebo |
Primary outcome
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
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).
51 secondary outcomes
Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase)
Time frame: Endpoint (Week 6)
Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase)
Time frame: Baseline through Endpoint (Week 6)
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)
Percentage of Participants With Recovery (Acute Phase)
Time frame: Baseline through Endpoint (Week 6 )
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
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)
Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase)
Time frame: Endpoint (Week 6)
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)
Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)
Time frame: Endpoint (Week 6)
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)
Percentage of Participants With Emergence of Mania During the Study (Acute Phase)
Time frame: Baseline through Endpoint (Week 6)
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)
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Weight (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Albumin (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
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)
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Hematocrit (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Hemoglobin (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Prolactin (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in Heart Rate (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)
Time frame: Baseline, Endpoint (Week 6)
Number of Participants With Adverse Events (Acute Phase)
Time frame: Baseline through Week 6 (Acute Phase)
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)
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)
Percentage of Participants With Recovery (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)
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)
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)
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)
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Change From Baseline to Endpoint in Weight (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24)
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)
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)
Change From Baseline to Endpoint in Chloride (Open-Label Phase)
Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24417745Katagiri 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.
- Derived from this study: PubMed 23672672Katagiri 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.
- Derived from this study: PubMed 22918966Tohen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Olanzapine in people with Depression, Bipolar, run by Eli Lilly and Company at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in China, Japan, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 May 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase) (time frame: Baseline, Endpoint (Week 6)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00510146, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2011.