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

This study has been completed.

Sponsor:

Information provided by:

Eli Lilly and Company

ClinicalTrials.gov Identifier:

NCT00129220

First received: August 8, 2005

Last updated: December 10, 2010

Last verified: December 2010

History of Changes

Results First Received: January 21, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Bipolar Disorder
Interventions:	Drug: olanzapine Drug: haloperidol Drug: placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Participant Flow for 2 periods

Period 1: Study Period II

	Olanzapine	Haloperidol	Placebo
STARTED	105	20	99
Received at Least One Dose of Study Drug	104	20	97
COMPLETED	72	8	52
NOT COMPLETED	33	12	47
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 2: Study Period III

	Olanzapine	Haloperidol	Placebo
STARTED	72	8	52
COMPLETED	59	7	42
NOT COMPLETED	13	1	10
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

Baseline Characteristics

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Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks
Total	Total of all reporting groups

Baseline Measures

	Olanzapine	Haloperidol	Placebo	Total
Number of Participants [units: participants]	104	20	97	221
Age [units: years] Mean ± Standard Deviation	43.1 ± 12.0	49.3 ± 11.9	42.5 ± 10.9	43.4 ± 11.6
Gender [units: participants]
Female	55	9	57	121
Male	49	11	40	100
Race/Ethnicity, Customized [units: participants]
Japanese	104	20	97	221
Region of Enrollment [units: participants]
Japan	104	20	97	221
Current Illness Episode: Manic versus Mixed [units: participants]
Manic	95	19	89	203
Mixed	9	1	8	18
Current Illness Episode: Psychotic versus Nonpsychotic [units: participants]
Psychotic	17	4	19	40
Nonpsychotic	87	16	78	181
Hospitalization Status [units: participants]
In-Patients	41	10	38	89
Out-Patients	63	10	59	132
Psychosis ^[1] [units: participants]
Mood-Congruent	16	4	19	39
Mood-Incongruent	1	0	0	1
17-Item Hamilton Depression Rating Scale Total Score ^[2] [units: units on a scale] Mean ± Standard Deviation	4.5 ± 3.9	4.1 ± 3.7	4.9 ± 4.5	4.7 ± 4.1
Age of Onset of Illness [units: years] Mean ± Standard Deviation	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) ^[3] [units: units on a scale] Mean ± Standard Deviation
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
Height [units: centimeters (cm)] Mean ± Standard Deviation	162.74 ± 8.07	162.10 ± 7.87	163.09 ± 9.66	162.84 ± 8.76
Length of Current Illness Episode [units: days] Mean ± Standard Deviation	34.6 ± 22.9	34.2 ± 22.0	33.5 ± 25.4	34.1 ± 23.9
Positive and Negative Syndrome Scale Positive Subscale Score ^[4] [units: units on a scale] Mean ± Standard Deviation	11.5 ± 4.8	11.3 ± 4.5	10.7 ± 4.7	11.1 ± 4.7
Weight [units: kilograms (kg)] Mean ± Standard Deviation	60.88 ± 11.69	59.20 ± 9.87	61.86 ± 13.78	61.17 ± 12.49
Young Mania Rating Scale (YMRS) Total Score ^[5] [units: units on a scale] Mean ± Standard Deviation	27.7 ± 5.9	26.6 ± 4.5	26.9 ± 5.6	27.3 ± 5.7

[1]	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)
[2]	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).
[3]	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).
[4]	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.
[5]	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.

Outcome Measures

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1. Primary:

Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score [ Time Frame: Baseline, 3 weeks ]

Measure Type	Primary
Measure Title	Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score
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.
Time Frame	Baseline, 3 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	104	20	97
Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score [units: units on a scale] Mean ± Standard Deviation	-12.6 ± 10.0	-14.3 ± 11.4	-6.8 ± 14.0

Statistical Analysis 1 for Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score

Groups ^[1]	Olanzapine vs. Placebo
Method ^[2]	ANCOVA
P Value ^[3]	<0.001
Least Squares Mean Difference ^[4]	-5.62
95% Confidence Interval	( -8.87 to -2.37 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Placebo.

2. Secondary:

Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) [ Time Frame: Baseline, 6 weeks ]

Measure Type	Secondary
Measure Title	Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS)
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.
Time Frame	Baseline, 6 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	104	20	97
Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) [units: units on a scale] Mean ± Standard Deviation	-16.0 ± 11.4	-14.7 ± 13.1	-10.1 ± 15.8

Statistical Analysis 1 for Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS)

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	ANCOVA
P Value ^[3]	0.774
Least Squares Mean Difference ^[4]	-0.78
95% Confidence Interval	( -6.15 to 4.59 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olazapine minus Haloperidol.

3. Secondary:

Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol) [ Time Frame: 6 weeks ]

Measure Type	Secondary
Measure Title	Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol)
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day
Haloperidol	haloperidol: 2.5 to 10 mg per day

Measured Values

	Olanzapine	Haloperidol
Number of Participants Analyzed [units: participants]	104	20
Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol) [units: percentage of participants]	44.2	20.0

Statistical Analysis 1 for Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol)

Groups ^[1]	All groups
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.064
Least Squares Mean Difference ^[4]	21.0
95% Confidence Interval	( 1.6 to 40.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Haloperidol.

4. Secondary:

Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness [ Time Frame: Baseline, 6 weeks ]

Measure Type	Secondary
Measure Title	Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	104	20	97
Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness [units: units on a scale] Mean ± Standard Deviation	-1.6 ± 1.5	-1.3 ± 1.8	-0.9 ± 1.7

Statistical Analysis 1 for Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	ANCOVA
P Value ^[3]	0.171
Least Squares Mean Difference ^[4]	-0.47
95% Confidence Interval	( -1.15 to 0.21 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Haloperidol.

5. Secondary:

Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale [ Time Frame: Baseline, 3 weeks, 6 weeks ]

Measure Type	Secondary
Measure Title	Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale
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 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	104	20	97
Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale [units: units on a scale] Mean ± Standard Deviation
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

Statistical Analysis 1 for Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale

Groups ^[1]	Olanzapine vs. Placebo
Method ^[2]	ANCOVA
P Value ^[3]	0.006
Least Squares Mean Difference ^[4]	-0.51
95% Confidence Interval	( -0.87 to -0.15 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 3-Week Change.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Placebo.

Statistical Analysis 2 for Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	ANCOVA
P Value ^[3]	0.722
Least Squares Mean Difference ^[4]	-0.13
95% Confidence Interval	( -0.82 to 0.57 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 6-Week Change.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Haloperidol.

6. Secondary:

Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks [ Time Frame: Baseline, 3 weeks, 6 weeks ]

Measure Type	Secondary
Measure Title	Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	104	20	97
Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks [units: percentage of participants]
3 Week Response Rate	51.0	65.0	44.3
6 Week Response Rate	67.3	65.0	55.7

Statistical Analysis 1 for Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks

Groups ^[1]	Olanzapine vs. Placebo
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.333
Mean Difference (Net) ^[4]	6.7
95% Confidence Interval	( -6.7 to 20.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 3-Week Response Rate.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.908
Mean Difference (Net) ^[4]	-1.3
95% Confidence Interval	( -21.0 to 18.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 6-Week Response Rate.
[4]	Other relevant estimation information:
	No text entered.

7. Secondary:

Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks [ Time Frame: 3 weeks, 6 weeks ]

Measure Type	Secondary
Measure Title	Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	104	20	97
Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks [units: percentage of participants]
3-Week Remission Rate	47.1	65.0	41.2
6-Week Remission Rate	63.5	60.0	52.6

Statistical Analysis 1 for Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks

Groups ^[1]	Olanzapine vs. Placebo
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.384
Least Squares Mean Difference ^[4]	5.9
95% Confidence Interval	( -7.3 to 19.2 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 3-Week Remission Rate.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Placebo.

Statistical Analysis 2 for Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.982
Least Squares Mean Difference ^[4]	0.3
95% Confidence Interval	( -21.3 to 21.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value is for 6-Week Remission Rate
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Haloperidol.

8. Secondary:

Percentage of Participants Who Switched to Symptomatic Depression [ Time Frame: 3 weeks, 6 weeks ]

Measure Type	Secondary
Measure Title	Percentage of Participants Who Switched to Symptomatic Depression
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set (participants who had baseline and post-baseline measurement) who had HAMD-17 total scores ≤7 at baseline.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	83	18	75
Percentage of Participants Who Switched to Symptomatic Depression [units: 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

Statistical Analysis 1 for Percentage of Participants Who Switched to Symptomatic Depression

Groups ^[1]	Olanzapine vs. Placebo
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.698
Mean Difference (Net) ^[4]	0.8
95% Confidence Interval	( -3.2 to 4.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 3-Week Symptomatic Depression Rate.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Percentage of Participants Who Switched to Symptomatic Depression

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.014
Mean Difference (Net) ^[4]	-14.1
95% Confidence Interval	( -31.7 to 3.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 6-Week Symptomatic Depression Rate.
[4]	Other relevant estimation information:
	No text entered.

9. Secondary:

Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Baseline, 3 weeks, 6 weeks ]

Measure Type	Secondary
Measure Title	Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS)
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.
Time Frame	Baseline, 3 weeks, 6 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	104	20	97
Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) [units: units on a scale] Mean ± Standard Deviation
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

Statistical Analysis 1 for Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS)

Groups ^[1]	Olanzapine vs. Placebo
Method ^[2]	ANCOVA
P Value ^[3]	0.019
Least Squares Mean Difference ^[4]	-1.48
95% Confidence Interval	( -2.71 to -0.25 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 3-Week Change.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Placebo.

Statistical Analysis 2 for Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS)

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	ANCOVA
P Value ^[3]	0.855
Least Squares Mean Difference ^[4]	-0.16
95% Confidence Interval	( -1.95 to 1.62 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 6-Week Change.
[4]	Other relevant estimation information:
	Least Squares Mean Difference = Olanzapine minus Haloperidol.

10. Secondary:

Percentage of Participants Who Switched to Syndromic Depression [ Time Frame: 3 weeks, 6 weeks ]

Measure Type	Secondary
Measure Title	Percentage of Participants Who Switched to Syndromic Depression
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Full Analysis Set (participants who had baseline and post-baseline measurement) who had manic (not mixed) episode at baseline.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	95	19	89
Percentage of Participants Who Switched to Syndromic Depression [units: 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

Statistical Analysis 1 for Percentage of Participants Who Switched to Syndromic Depression

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.136
Mean Difference (Net) ^[4]	-4.6
95% Confidence Interval	( -14.9 to 5.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for 6-Week Syndromic Depression Rate.
[4]	Other relevant estimation information:
	No text entered.

11. Secondary:

Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score [ Time Frame: Baseline to 6 weeks ]

Measure Type	Secondary
Measure Title	Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score
Measure 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
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Olanzapine	olanzapine: 5 to 20 mg per day for 6 weeks
Haloperidol	haloperidol: 2.5 to 10 mg per day for 6 weeks
Placebo	placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks

Measured Values

	Olanzapine	Haloperidol	Placebo
Number of Participants Analyzed [units: participants]	105	20	96
Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score [units: units on a scale] Mean ± Standard Deviation
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

Statistical Analysis 1 for Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score

Groups ^[1]	Olanzapine vs. Haloperidol
Method ^[2]	Wilcoxon Rank Sum
P Value ^[3]	0.003

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value for Maximum Change from Baseline.

Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Identified errors were corrected.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979

No publications provided by Eli Lilly and Company

Publications automatically indexed to this study:

Katagiri H, Takita Y, Tohen M, Higuchi T, Kanba S, Takahashi M. Efficacy and safety of olanzapine in the treatment of Japanese patients with bipolar I disorder in a current manic or mixed episode: a randomized, double-blind, placebo- and haloperidol-controlled study. J Affect Disord. 2012 Feb;136(3):476-84. Epub 2011 Nov 30.

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00129220 History of Changes
Other Study ID Numbers:	9636, F1D-JE-BMAC
Study First Received:	August 8, 2005
Results First Received:	January 21, 2010
Last Updated:	December 10, 2010
Health Authority:	Japan: Ministry of Health, Labor and Welfare

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