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Trial of Olanzapine in Patients With Manic or Mixed Episode of Bipolar I Disorder

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ClinicalTrials.gov Identifier: NCT00129220
Recruitment Status : Completed
First Posted : August 11, 2005
Results First Posted : February 15, 2010
Last Update Posted : December 28, 2010
Sponsor:
Information provided by:
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Bipolar Disorder
Interventions Drug: olanzapine
Drug: haloperidol
Drug: placebo
Enrollment 224
Recruitment Details  
Pre-assignment Details Study Period I was a week-long Screening Period. Study Period II was a 3-week-long Early Double-Blind Period. Study Period III was a 3-week-long Last Double-Blind Period.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description olanzapine: 5 to 20 mg per day for 6 weeks haloperidol: 2.5 to 10 mg per day for 6 weeks placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Period Title: Study Period II
Started 105 20 99
Received at Least One Dose of Study Drug 104 20 97
Completed 72 8 52
Not Completed 33 12 47
Reason Not Completed
Adverse Event             9             5             7
Lack of Efficacy             15             1             28
Entry Criteria Not Met             2             0             2
Protocol Violation             4             2             1
Physician Decision             0             1             0
Withdrawal by Subject             1             3             4
Reason Not Specified             2             0             5
Period Title: Study Period III
Started 72 8 52
Completed 59 7 42
Not Completed 13 1 10
Reason Not Completed
Adverse Event             1             0             3
Protocol Violation             1             1             2
Withdrawal by Subject             1             0             3
Sponsor Decision             1             0             0
Reason Not Specified             9             0             2
Arm/Group Title Olanzapine Haloperidol Placebo Total
Hide Arm/Group Description olanzapine: 5 to 20 mg per day for 6 weeks haloperidol: 2.5 to 10 mg per day for 6 weeks placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks Total of all reporting groups
Overall Number of Baseline Participants 104 20 97 221
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 104 participants 20 participants 97 participants 221 participants
43.1  (12.0) 49.3  (11.9) 42.5  (10.9) 43.4  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 20 participants 97 participants 221 participants
Female
55
  52.9%
9
  45.0%
57
  58.8%
121
  54.8%
Male
49
  47.1%
11
  55.0%
40
  41.2%
100
  45.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Japanese Number Analyzed 104 participants 20 participants 97 participants 221 participants
104 20 97 221
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 104 participants 20 participants 97 participants 221 participants
104 20 97 221
Current Illness Episode: Manic versus Mixed  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 104 participants 20 participants 97 participants 221 participants
Manic 95 19 89 203
Mixed 9 1 8 18
Current Illness Episode: Psychotic versus Nonpsychotic  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 104 participants 20 participants 97 participants 221 participants
Psychotic 17 4 19 40
Nonpsychotic 87 16 78 181
Hospitalization Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 104 participants 20 participants 97 participants 221 participants
In-Patients 41 10 38 89
Out-Patients 63 10 59 132
Psychosis   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 104 participants 20 participants 97 participants 221 participants
Mood-Congruent 16 4 19 39
Mood-Incongruent 1 0 0 1
[1]
Measure Description: Type of psychosis for those participants who had a current illness episode of psychotic (total number of participants with data in this baseline measure will be less than the total in each arm)
17-Item Hamilton Depression Rating Scale Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 104 participants 20 participants 97 participants 221 participants
4.5  (3.9) 4.1  (3.7) 4.9  (4.5) 4.7  (4.1)
[1]
Measure Description: 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).
Age of Onset of Illness  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 104 participants 20 participants 97 participants 221 participants
31.2  (11.6) 37.7  (12.5) 30.9  (10.7) 31.6  (11.4)
Clinical Global Impression-Severity of Illness, Bipolar Version (CGI-BP)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 104 participants 20 participants 97 participants 221 participants
Mania 4.2  (1.0) 4.6  (0.8) 4.1  (1.1) 4.2  (1.0)
Depression 1.3  (0.6) 1.1  (0.2) 1.3  (0.7) 1.2  (0.6)
Overall Mood 4.1  (1.0) 4.4  (1.2) 4.1  (1.1) 4.1  (1.1)
[1]
Measure Description: A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of manic symptoms, depressive symptoms, and overall mood symptoms. Each of the three symptoms are on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 104 participants 20 participants 97 participants 221 participants
162.74  (8.07) 162.10  (7.87) 163.09  (9.66) 162.84  (8.76)
Length of Current Illness Episode  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 104 participants 20 participants 97 participants 221 participants
34.6  (22.9) 34.2  (22.0) 33.5  (25.4) 34.1  (23.9)
Positive and Negative Syndrome Scale Positive Subscale Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 104 participants 20 participants 97 participants 221 participants
11.5  (4.8) 11.3  (4.5) 10.7  (4.7) 11.1  (4.7)
[1]
Measure Description: Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total Positive Subscale scores range from 7 to 49. For this study, the score was converted to 0 to 6 for each item range; hence, the total positive subscale score ranges from 0 to 42.
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 104 participants 20 participants 97 participants 221 participants
60.88  (11.69) 59.20  (9.87) 61.86  (13.78) 61.17  (12.49)
Young Mania Rating Scale (YMRS) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 104 participants 20 participants 97 participants 221 participants
27.7  (5.9) 26.6  (4.5) 26.9  (5.6) 27.3  (5.7)
[1]
Measure Description: 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.
1.Primary Outcome
Title Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score
Hide Description 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.
Time Frame Baseline, 3 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 104 20 97
Mean (Standard Deviation)
Unit of Measure: units on a scale
-12.6  (10.0) -14.3  (11.4) -6.8  (14.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -5.62
Confidence Interval (2-Sided) 95%
-8.87 to -2.37
Estimation Comments Least Squares Mean Difference = Olanzapine minus Placebo.
2.Secondary Outcome
Title Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS)
Hide Description 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.
Time Frame Baseline, 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 104 20 97
Mean (Standard Deviation)
Unit of Measure: units on a scale
-16.0  (11.4) -14.7  (13.1) -10.1  (15.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.774
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.78
Confidence Interval (2-Sided) 95%
-6.15 to 4.59
Estimation Comments Least Squares Mean Difference = Olazapine minus Haloperidol.
3.Secondary Outcome
Title Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol)
Hide Description Remission of bipolar disorder was defined as completing the 6-week period with meeting the criteria for Young Mania Rating Scale (YMRS) total score of 12 or less and 17-Item Hamilton Depression Rating Scale (HAMD-17) total scores of 7 or less at Week 6. YMRS is an 11-item scale measuring severity of manic episodes; total score ranges = 0 (normal) to 60 (severe). The 17-item HAMD measures depression severity; total score ranges = 0 (normal) to 52 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100.
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
Arm/Group Title Olanzapine Haloperidol
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day
haloperidol: 2.5 to 10 mg per day
Overall Number of Participants Analyzed 104 20
Measure Type: Number
Unit of Measure: percentage of participants
44.2 20.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.064
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 21.0
Confidence Interval (2-Sided) 95%
1.6 to 40.4
Estimation Comments Least Squares Mean Difference = Olanzapine minus Haloperidol.
4.Secondary Outcome
Title Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness
Hide Description A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of overall mood symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time Frame Baseline, 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 104 20 97
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.6  (1.5) -1.3  (1.8) -0.9  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.171
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-1.15 to 0.21
Estimation Comments Least Squares Mean Difference = Olanzapine minus Haloperidol.
5.Secondary Outcome
Title Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale
Hide Description A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of manic symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time Frame Baseline, 3 weeks, 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 104 20 97
Mean (Standard Deviation)
Unit of Measure: units on a scale
3-Week Change -1.2  (1.2) -1.7  (1.7) -0.6  (1.5)
6-Week Change -1.7  (1.5) -1.9  (1.9) -1.0  (1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments P-value for 3-Week Change.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-0.87 to -0.15
Estimation Comments Least Squares Mean Difference = Olanzapine minus Placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.722
Comments P-value for 6-Week Change.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.82 to 0.57
Estimation Comments Least Squares Mean Difference = Olanzapine minus Haloperidol.
6.Secondary Outcome
Title Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks
Hide Description Participants who had 50 percent or more decrease from the baseline in YMRS total scores were defined as a responder. 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. Response Rate (percent) = number of patients meeting response criterion for manic symptom divided by number of patients in treatment arm, multiplied by 100.
Time Frame Baseline, 3 weeks, 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 104 20 97
Measure Type: Number
Unit of Measure: percentage of participants
3 Week Response Rate 51.0 65.0 44.3
6 Week Response Rate 67.3 65.0 55.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.333
Comments P-value for 3-Week Response Rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.7
Confidence Interval (2-Sided) 95%
-6.7 to 20.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.908
Comments P-value for 6-Week Response Rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-21.0 to 18.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks
Hide Description Participants who had a YMRS total score of 12 or less were considered to be in remission of manic symptoms. YMRS is an 11-item scale that measures severity of manic episodes; total score ranges from 0 (normal) to 60 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100.
Time Frame 3 weeks, 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 104 20 97
Measure Type: Number
Unit of Measure: percentage of participants
3-Week Remission Rate 47.1 65.0 41.2
6-Week Remission Rate 63.5 60.0 52.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.384
Comments P-value for 3-Week Remission Rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 5.9
Confidence Interval (2-Sided) 95%
-7.3 to 19.2
Estimation Comments Least Squares Mean Difference = Olanzapine minus Placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.982
Comments P-value is for 6-Week Remission Rate
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-21.3 to 21.8
Estimation Comments Least Squares Mean Difference = Olanzapine minus Haloperidol.
8.Secondary Outcome
Title Percentage of Participants Who Switched to Symptomatic Depression
Hide Description Switch to symptomatic depression was defined as HAMD-17 total score ≥13 at any time in the participants with HAMD-17 total scores ≤7 at baseline. 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).
Time Frame 3 weeks, 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (participants who had baseline and post-baseline measurement) who had HAMD-17 total scores ≤7 at baseline.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 83 18 75
Measure Type: Number
Unit of Measure: percentage of participants
3-Week Symptomatic Depression Rate 2.4 16.7 1.3
6-Week Symptomatic Depression Rate 2.4 16.7 2.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.698
Comments P-value for 3-Week Symptomatic Depression Rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-3.2 to 4.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments P-value for 6-Week Symptomatic Depression Rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -14.1
Confidence Interval (2-Sided) 95%
-31.7 to 3.4
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS)
Hide Description Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total Positive Subscale scores range from 7 to 49. For this study, the score was converted to 0 to 6 for each item range; hence, the total positive subscale score ranges from 0 to 42.
Time Frame Baseline, 3 weeks, 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 104 20 97
Mean (Standard Deviation)
Unit of Measure: units on a scale
3-Week Change -1.8  (4.1) -1.8  (4.3) -0.0  (5.3)
6-Week Change -2.2  (4.4) -1.6  (4.3) -0.3  (5.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments P-value for 3-Week Change.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.48
Confidence Interval (2-Sided) 95%
-2.71 to -0.25
Estimation Comments Least Squares Mean Difference = Olanzapine minus Placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.855
Comments P-value for 6-Week Change.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-1.95 to 1.62
Estimation Comments Least Squares Mean Difference = Olanzapine minus Haloperidol.
10.Secondary Outcome
Title Percentage of Participants Who Switched to Syndromic Depression
Hide Description Switch to syndromic depression was operationally defined by meeting both of the following criteria: At baseline, the symptoms did not meet the criteria for a mixed episode based on the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). The critiera were met for a Major Depressive Episode (MDE), at any point after randomization, based on DSM-IV-TR. Rather than the 2-week period required for an MDE in the DSM-IV-TR, the patient had to meet the criteria of an MDE for at least 7 consecutive days (during Weeks 1 through 6).
Time Frame 3 weeks, 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (participants who had baseline and post-baseline measurement) who had manic (not mixed) episode at baseline.
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description:
olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 95 19 89
Measure Type: Number
Unit of Measure: percentage of participants
3-Week Syndromic Depression Rate 0.0 5.3 0.0
6-Week Syndromic Depression Rate 1.1 5.3 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.136
Comments P-value for 6-Week Syndromic Depression Rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.6
Confidence Interval (2-Sided) 95%
-14.9 to 5.7
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score
Hide Description Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the sum of the 8 item scores, for a total range of 0 (normal) to 32 (severe).
Time Frame Baseline to 6 weeks
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Hide Analysis Population Description
Participants in the Safety Analysis Set (participants who had baseline and post-baseline measurements). Participants were included in the treatment group for which they actually received treatment.
Arm/Group Title Olanzapine Haloperidol Placebo
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olanzapine: 5 to 20 mg per day for 6 weeks
haloperidol: 2.5 to 10 mg per day for 6 weeks
placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Overall Number of Participants Analyzed 105 20 96
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 0.20  (0.66) 0.50  (1.19) 0.30  (0.91)
Maximum Change from Baseline 0.70  (1.51) 2.70  (2.89) 0.09  (1.09)
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Statistical Analysis Overview Comparison Group Selection Olanzapine, Haloperidol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments P-value for Maximum Change from Baseline.
Method Wilcoxon Rank Sum
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Olanzapine Haloperidol Placebo
Hide Arm/Group Description olanzapine: 5 to 20 mg per day for 6 weeks haloperidol: 2.5 to 10 mg per day for 6 weeks placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
All-Cause Mortality
Olanzapine Haloperidol Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Olanzapine Haloperidol Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/105 (0.95%)      0/20 (0.00%)      3/96 (3.13%)    
Nervous system disorders       
Status epilepticus  1  0/105 (0.00%)  0 0/20 (0.00%)  0 1/96 (1.04%)  1
Psychiatric disorders       
Bipolar I disorder  1  1/105 (0.95%)  1 0/20 (0.00%)  0 1/96 (1.04%)  1
Mania  1  0/105 (0.00%)  0 0/20 (0.00%)  0 1/96 (1.04%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Olanzapine Haloperidol Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   78/105 (74.29%)      14/20 (70.00%)      64/96 (66.67%)    
Eye disorders       
Asthenopia  1  0/105 (0.00%)  0 0/20 (0.00%)  0 2/96 (2.08%)  2
Gastrointestinal disorders       
Cheilitis  1  1/105 (0.95%)  1 1/20 (5.00%)  1 0/96 (0.00%)  0
Constipation  1  10/105 (9.52%)  10 2/20 (10.00%)  2 3/96 (3.13%)  3
Diarrhoea  1  1/105 (0.95%)  1 0/20 (0.00%)  0 4/96 (4.17%)  4
Nausea  1  2/105 (1.90%)  2 0/20 (0.00%)  0 2/96 (2.08%)  2
Salivary hypersecretion  1  0/105 (0.00%)  0 1/20 (5.00%)  1 0/96 (0.00%)  0
Vomiting  1  2/105 (1.90%)  2 1/20 (5.00%)  1 1/96 (1.04%)  1
General disorders       
Hunger  1  3/105 (2.86%)  3 0/20 (0.00%)  0 0/96 (0.00%)  0
Malaise  1  6/105 (5.71%)  6 2/20 (10.00%)  2 4/96 (4.17%)  4
Oedema  1  0/105 (0.00%)  0 0/20 (0.00%)  0 2/96 (2.08%)  2
Thirst  1  16/105 (15.24%)  16 1/20 (5.00%)  1 2/96 (2.08%)  2
Infections and infestations       
Nasopharyngitis  1  9/105 (8.57%)  9 2/20 (10.00%)  2 9/96 (9.38%)  9
Injury, poisoning and procedural complications       
Contusion  1  4/105 (3.81%)  5 0/20 (0.00%)  0 1/96 (1.04%)  1
Fall  1  2/105 (1.90%)  2 1/20 (5.00%)  1 1/96 (1.04%)  1
Subcutaneous haematoma  1  0/105 (0.00%)  0 1/20 (5.00%)  1 0/96 (0.00%)  0
Investigations       
Blood pressure decreased  1  0/105 (0.00%)  0 1/20 (5.00%)  1 0/96 (0.00%)  0
Blood triglycerides increased  1  5/105 (4.76%)  5 0/20 (0.00%)  0 2/96 (2.08%)  2
Electrocardiogram qt prolonged  1  1/105 (0.95%)  1 0/20 (0.00%)  0 2/96 (2.08%)  2
Glycosylated haemoglobin increased  1  0/105 (0.00%)  0 0/20 (0.00%)  0 2/96 (2.08%)  2
Weight decreased  1  0/105 (0.00%)  0 0/20 (0.00%)  0 2/96 (2.08%)  2
Weight increased  1  10/105 (9.52%)  10 1/20 (5.00%)  1 4/96 (4.17%)  4
Metabolism and nutrition disorders       
Increased appetite  1  7/105 (6.67%)  7 1/20 (5.00%)  1 4/96 (4.17%)  4
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/105 (0.95%)  1 1/20 (5.00%)  1 0/96 (0.00%)  0
Muscular weakness  1  0/105 (0.00%)  0 0/20 (0.00%)  0 2/96 (2.08%)  2
Osteoarthritis  1  0/105 (0.00%)  0 1/20 (5.00%)  1 0/96 (0.00%)  0
Nervous system disorders       
Akathisia  1  3/105 (2.86%)  3 3/20 (15.00%)  5 0/96 (0.00%)  0
Dizziness  1  7/105 (6.67%)  8 0/20 (0.00%)  0 1/96 (1.04%)  2
Dystonia  1  0/105 (0.00%)  0 3/20 (15.00%)  3 1/96 (1.04%)  1
Headache  1  5/105 (4.76%)  5 1/20 (5.00%)  1 3/96 (3.13%)  3
Sedation  1  2/105 (1.90%)  2 1/20 (5.00%)  1 0/96 (0.00%)  0
Somnolence  1  25/105 (23.81%)  26 3/20 (15.00%)  3 15/96 (15.63%)  17
Tremor  1  3/105 (2.86%)  3 2/20 (10.00%)  2 1/96 (1.04%)  1
Psychiatric disorders       
Depressive symptom  1  0/105 (0.00%)  0 1/20 (5.00%)  1 0/96 (0.00%)  0
Insomnia  1  1/105 (0.95%)  1 1/20 (5.00%)  1 1/96 (1.04%)  1
Mania  1  1/105 (0.95%)  1 1/20 (5.00%)  1 0/96 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Pharyngolaryngeal pain  1  1/105 (0.95%)  1 0/20 (0.00%)  0 2/96 (2.08%)  2
Skin and subcutaneous tissue disorders       
Pruritus  1  0/105 (0.00%)  0 1/20 (5.00%)  1 1/96 (1.04%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
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Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00129220     History of Changes
Other Study ID Numbers: 9636
F1D-JE-BMAC ( Other Identifier: Eli Lilly and Company )
First Submitted: August 8, 2005
First Posted: August 11, 2005
Results First Submitted: January 21, 2010
Results First Posted: February 15, 2010
Last Update Posted: December 28, 2010