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

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

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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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

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 ]

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2. Secondary:

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

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3. Secondary:

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

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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 ]

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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 ]

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6. Secondary:

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

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7. Secondary:

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

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8. Secondary:

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

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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 ]

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10. Secondary:

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

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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 ]

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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

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