Safety and Efficacy of Olanzapine in the Long-term Treatment for Bipolar I Disorder, Depressed

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00618748
• Collaborator: (none)
• Enrollment: 101
• Locations: 10
• Arms: 3
• Duration (Months): 31
• Patients Per Site: 10.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To assess the efficacy and safety of olanzapine in the long-term treatment for patients with bipolar I disorder, depressed.

Condition or Disease	Intervention/Treatment	Phase
Bipolar I Disorder	Drug: Olanzapine	Phase 3

Detailed Description

This is an open-label, multi-center, long-term treatment study conducted only in Japanese sites. The subjects are patients who fulfill the diagnostic criteria for bipolar I disorder, most recent episode depressed, as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) (296.50=unspecified, 296.52=moderate severity, 296.53=severe without psychotic features, 296.54=severe with psychotic features), who have completed Study HGMP (NCT#00510146) and patients who did not participate in Study HGMP who have been recruited to participate in Study HGMS.

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Olanzapine (LY170053) in the Long-term Treatment for Patients With Bipolar I Disorder, Depressed
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pre-Olanzapine Participants who received olanzapine 5-20 mg/day in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Drug: Olanzapine; 5-20 mg/day, oral, daily; Other Names: LY170053
Experimental: Pre-Placebo Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Drug: Olanzapine; 5-20 mg/day, oral, daily; Other Names: LY170053
Experimental: New Olanzapine Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.	Drug: Olanzapine; 5-20 mg/day, oral, daily; Other Names: LY170053

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events Leading to Discontinuation [Baseline through 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

   An adverse event (AE) is an untoward medical event associated with the use of the study drug or study procedure, whether or not it is considered related to the study drug or study procedure. Results presented are the percentage of participants who experienced an adverse event that resulted in the discontinuation of the study.

Secondary Outcome Measures

1. Change From Baseline in Glucose and Lipid Panel at Week 24 or Week 48 Endpoint [baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

2. Change From Baseline in Weight at Week 24 or Week 48 Endpoint [baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

3. Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 24 or Week 48 Endpoint [baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

   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).

4. Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 24 or Week 48 Endpoint [baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

   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.

5. Change From Baseline in Clinical Global Improvement- Bipolar (CGI-BP) at Week 24 or Week 48 Endpoint [baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

   CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The scores for mania, depression, and overall illness each range from 1 (normal, not ill) to 7 (very seriously ill).

6. Percentage of Participants With Emergence of Mania at Week 24 or Week 48 [24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

   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.

7. Percentage of Participants With High Suicidality at Week 24 or Week 48 [24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

   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).

8. Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Week 24 or Week 48 [24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

   EPS symptoms measured by DIEPSS are grouped into 4 categories: Parkinsonism, akathisia, dystonia, and dyskinesia. Severity ranges from level 0 (none, normal) to 4 (severe). A participant is deemed to have EPS at endpoint if they have an abnormal endpoint. Normal baseline Parkinsonism is defined as a score not ≥3 on 1 item or ≥2 on 2 items; abnormal endpoint is a score ≥3 on 1 item or ≥2 on 2 items, or an increase of 3 on Parkinsonism total. Normal 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.

9. Change From Baseline in Hemoglobin (HbA1c) at Week 24 or Week 48 Endpoint [baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

   HbA1c is a test that measures the amount of glycated hemoglobin in the blood over prolonged periods of time.

10. Change From Baseline in Prolactin at Week 24 or Week 48 Endpoint [baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

11. Change From Baseline to in QTcF at Week 24 or Week 48 Endpoint [baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)]

    Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients must be aged 18 to less than 75 years.

2. 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.

3. All female patients must test negative for pregnancy.

4. 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.

5. Male patients who are not surgically sterilized must agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug.

6. Patients must fulfill the diagnostic criteria for bipolar I disorder, most recent episode depressed, as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR).

7. Patients must have experienced, in the opinion of the investigator, at least one previous manic or mixed episode, as defined in the DSM-IV-TR.

8. Patients must have a current Young Mania Rating Scale (YMRS) Total score =<8.

Exclusion Criteria:

1. Is investigator site personnel directly affiliated with this study or their immediate families.

2. Is a Lilly employee.

3. Has previously completed or withdrawn from this study or any other study investigating olanzapine.

4. Is pregnant or nursing.

5. Has a serious, unstable illness such that death is anticipated within 1 year or intensive care unit hospitalization for the disease is anticipated within 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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.	Aichi		Japan	470-1168
2	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.	Chiba		Japan	270-1694
3	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		Japan	731-0501
4	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.	Iwate		Japan	023-0801
5	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.	Kanagawa		Japan	231-0027
6	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.	Kyoto		Japan	616-8421
7	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.	Saitama		Japan	332-0012
8	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		Japan	525-0037
9	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		Japan	170-0002
10	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.	Yamaguchi		Japan	755-8505

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4599) or 1-317-615-4559 Mon-Fri 9 AM-5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00618748
• Other Study ID Numbers: 11682; F1D-JE-HGMS
• First Posted: Feb 20, 2008
• Last Update Posted: Jul 27, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: Bipolar
• Additional relevant MeSH terms: Disease; Olanzapine

Study Results

Participant Flow

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Period Title: Overall Study
STARTED	56	25	20
COMPLETED	45	20	6
NOT COMPLETED	11	5	14

Baseline Characteristics

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine	Total
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.	Total of all reporting groups
Overall Participants	56	25	20	101
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.31 (10.48)	37.53 (7.64)	39.13 (9.56)	38.84 (9.61)
Sex: Female, Male (Count of Participants)
Female	34 60.7%	14 56%	13 65%	61 60.4%
Male	22 39.3%	11 44%	7 35%	40 39.6%
Race/Ethnicity, Customized (participants) [Number]
East Asian	56 100%	25 100%	20 100%	101 100%
Region of Enrollment (participants) [Number]
Japan	56 100%	25 100%	20 100%	101 100%
Montgomery- Asberg Depression Rating Scale (MADRS) Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.05 (7.50)	9.72 (6.48)	16.45 (9.03)	10.13 (8.18)
Young Mania Rating Scale (YMRS) Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.38 (1.10)	0.40 (0.76)	0.45 (0.83)	0.40 (0.97)
Clinical Global Improvement- Bipolar (CGI-BP) - Mania (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.09 (0.35)	1.00 (0.00)	1.00 (0.00)	1.05 (0.26)
CGI-BP - Depression (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.23 (0.95)	2.48 (0.82)	3.55 (1.15)	2.55 (1.08)
CGI-BP - Overall (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.20 (0.92)	2.40 (0.82)	3.25 (1.02)	2.46 (1.00)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events Leading to Discontinuation
Description	An adverse event (AE) is an untoward medical event associated with the use of the study drug or study procedure, whether or not it is considered related to the study drug or study procedure. Results presented are the percentage of participants who experienced an adverse event that resulted in the discontinuation of the study.
Time Frame	Baseline through 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

All randomized Participants.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Number [percentage of participants]	7.1 12.7%	12.0 48%	40.0 200%

2. Secondary Outcome

Title	Change From Baseline in Glucose and Lipid Panel at Week 24 or Week 48 Endpoint
Time Frame	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and the specified visit result.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Glucose, Fasting	0.03 (0.47)	0.37 (0.55)	0.68 (1.31)
Cholesterol	0.033 (0.699)	0.040 (0.716)	0.086 (1.031)
Low-density lipoprotein ( LDL) Cholesterol	0.141 (0.676)	-0.034 (0.731)	0.008 (0.855)
High-density lipoprotein ( HDL) Cholesterol	-0.036 (0.221)	-0.046 (0.212)	-0.074 (0.239)
Triglycerides	-0.108 (0.543)	0.485 (1.415)	0.382 (1.270)

3. Secondary Outcome

Title	Change From Baseline in Weight at Week 24 or Week 48 Endpoint
Time Frame	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and the specified visit result.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Mean (Standard Deviation) [kilograms]	0.29 (2.79)	0.92 (3.02)	5.36 (4.34)

4. Secondary Outcome

Title	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 24 or Week 48 Endpoint
Description	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).
Time Frame	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Mean (Standard Deviation) [units on a scale]	-0.2 (8.3)	-0.4 (6.5)	-5.8 (11.6)

5. Secondary Outcome

Title	Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 24 or Week 48 Endpoint
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, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Mean (Standard Deviation) [units on a scale]	0.4 (1.5)	-0.2 (1.0)	-0.1 (1.7)

6. Secondary Outcome

Title	Change From Baseline in Clinical Global Improvement- Bipolar (CGI-BP) at Week 24 or Week 48 Endpoint
Description	CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The scores for mania, depression, and overall illness each range from 1 (normal, not ill) to 7 (very seriously ill).
Time Frame	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
CGI-BP Mania	-0.1 (0.4)	0.1 (0.3)	0.1 (0.2)
CGI-BP Depression	-0.3 (0.9)	-0.0 (0.9)	-1.1 (1.3)
CGI-BP Overall Bipolar Illness	-0.3 (1.0)	-0.1 (0.7)	-0.9 (1.1)

7. Secondary Outcome

Title	Percentage of Participants With Emergence of Mania at Week 24 or Week 48
Description	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.
Time Frame	24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

All Randomized participants.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Number [percentage of participants]	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Percentage of Participants With High Suicidality at Week 24 or Week 48
Description	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).
Time Frame	24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and the specified visit value.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Number [percentage of participants]	3.6 6.4%	0 0%	0 0%

9. Secondary Outcome

Title	Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Week 24 or Week 48
Description	EPS symptoms measured by DIEPSS are grouped into 4 categories: Parkinsonism, akathisia, dystonia, and dyskinesia. Severity ranges from level 0 (none, normal) to 4 (severe). A participant is deemed to have EPS at endpoint if they have an abnormal endpoint. Normal baseline Parkinsonism is defined as a score not ≥3 on 1 item or ≥2 on 2 items; abnormal endpoint is a score ≥3 on 1 item or ≥2 on 2 items, or an increase of 3 on Parkinsonism total. Normal 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.
Time Frame	24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with a normal baseline and an endpoint result. For Parkinsonism, normal baseline is defined as a score not ≥3 on 1 item or ≥2 on 2 items. Normal baseline akathisia, dystonia and dyskinesia is defined as a score <2.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Akathisia	0 0%	0 0%	0 0%
Dyskinesia	0 0%	0 0%	0 0%
Dystonia	0 0%	0 0%	0 0%
Parkinsonism	3.6 6.4%	0 0%	5.0 25%

10. Secondary Outcome

Title	Change From Baseline in Hemoglobin (HbA1c) at Week 24 or Week 48 Endpoint
Description	HbA1c is a test that measures the amount of glycated hemoglobin in the blood over prolonged periods of time.
Time Frame	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and the specified visit result.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Mean (Standard Deviation) [percentage of glycated hemoglobin]	-0.016 (0.259)	0.036 (0.243)	0.180 (0.282)

11. Secondary Outcome

Title	Change From Baseline in Prolactin at Week 24 or Week 48 Endpoint
Time Frame	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and the specified visit result.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	25	20
Mean (Standard Deviation) [microgram/Liter]	-1.669 (10.498)	-0.388 (14.179)	3.383 (18.731)

12. Secondary Outcome

Title	Change From Baseline to in QTcF at Week 24 or Week 48 Endpoint
Description	Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval)
Time Frame	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Outcome Measure Data

Analysis Population Description

Participants with non-missing baseline value and the specified visit result.

Arm/Group Title	Pre-Olanzapine	Pre-Placebo	New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
Measure Participants	56	24	20
Mean (Standard Deviation) [millisecond (msec)]	-1.7 (16.6)	-8.5 (13.1)	-3.4 (13.9)

Adverse Events

Arm/Group Title	Pre-Olanzapine		Pre-Placebo		New Olanzapine
Arm/Group Description	Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.		Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.		Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.
All Cause Mortality
	Pre-Olanzapine		Pre-Placebo		New Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Pre-Olanzapine		Pre-Placebo		New Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/56 (1.8%)		0/25 (0%)		1/20 (5%)
Gastrointestinal disorders
Pancreatitis acute	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Hepatobiliary disorders
Cholecystitis acute	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Depressive symptom	1/56 (1.8%)	1	0/25 (0%)	0	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Pre-Olanzapine		Pre-Placebo		New Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/56 (60.7%)		13/25 (52%)		20/20 (100%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/56 (0%)	0	1/25 (4%)	1	0/20 (0%)	0
Ear and labyrinth disorders
Inner ear disorder	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Endocrine disorders
Hyperprolactinaemia	3/56 (5.4%)	5	0/25 (0%)	0	0/20 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Abdominal pain upper	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Constipation	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Diarrhoea	1/56 (1.8%)	1	0/25 (0%)	0	1/20 (5%)	1
Dry mouth	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Nausea	3/56 (5.4%)	3	0/25 (0%)	0	1/20 (5%)	2
Vomiting	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
General disorders
Fatigue	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Irritability	0/56 (0%)	0	0/25 (0%)	0	2/20 (10%)	2
Oedema peripheral	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Thirst	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Hepatobiliary disorders
Hepatic function abnormal	0/56 (0%)	0	2/25 (8%)	2	0/20 (0%)	0
Infections and infestations
Empyema	0/56 (0%)	0	1/25 (4%)	1	0/20 (0%)	0
Influenza	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Nasopharyngitis	7/56 (12.5%)	9	1/25 (4%)	1	3/20 (15%)	3
Injury, poisoning and procedural complications
Arthropod sting	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Investigations
Alanine aminotransferase increased	1/56 (1.8%)	1	0/25 (0%)	0	4/20 (20%)	5
Aspartate aminotransferase increased	1/56 (1.8%)	1	0/25 (0%)	0	2/20 (10%)	2
Blood cholesterol increased	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Blood creatine phosphokinase increased	0/56 (0%)	0	1/25 (4%)	1	4/20 (20%)	5
Blood creatinine increased	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Blood glucose increased	0/56 (0%)	0	1/25 (4%)	1	0/20 (0%)	0
Blood lactate dehydrogenase increased	0/56 (0%)	0	1/25 (4%)	1	0/20 (0%)	0
Blood pressure increased	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Blood prolactin increased	4/56 (7.1%)	4	1/25 (4%)	1	0/20 (0%)	0
Blood triglycerides decreased	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Blood triglycerides increased	0/56 (0%)	0	2/25 (8%)	2	2/20 (10%)	2
Electrocardiogram QT prolonged	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Glucose urine present	1/56 (1.8%)	1	1/25 (4%)	1	0/20 (0%)	0
Glycosylated haemoglobin increased	0/56 (0%)	0	1/25 (4%)	1	0/20 (0%)	0
High density lipoprotein increased	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Liver function test abnormal	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Neutrophil count decreased	1/56 (1.8%)	1	0/25 (0%)	0	1/20 (5%)	1
Neutrophil count increased	0/56 (0%)	0	1/25 (4%)	1	0/20 (0%)	0
Protein urine present	1/56 (1.8%)	1	1/25 (4%)	1	0/20 (0%)	0
Urine ketone body present	1/56 (1.8%)	1	1/25 (4%)	1	0/20 (0%)	0
Weight increased	3/56 (5.4%)	3	1/25 (4%)	1	14/20 (70%)	15
White blood cell count decreased	2/56 (3.6%)	2	0/25 (0%)	0	1/20 (5%)	1
White blood cell count increased	0/56 (0%)	0	1/25 (4%)	1	0/20 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/56 (1.8%)	1	0/25 (0%)	0	3/20 (15%)	3
Glucose tolerance impaired	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Hyperlipidaemia	1/56 (1.8%)	1	0/25 (0%)	0	1/20 (5%)	1
Increased appetite	0/56 (0%)	0	0/25 (0%)	0	9/20 (45%)	9
Musculoskeletal and connective tissue disorders
Arthralgia	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Back pain	2/56 (3.6%)	2	0/25 (0%)	0	2/20 (10%)	2
Nervous system disorders
Akathisia	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	3
Dizziness	1/56 (1.8%)	1	0/25 (0%)	0	1/20 (5%)	1
Dysarthria	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Dystonia	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Headache	4/56 (7.1%)	4	3/25 (12%)	3	2/20 (10%)	2
Hypersomnia	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Parkinsonism	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Somnolence	2/56 (3.6%)	2	0/25 (0%)	0	5/20 (25%)	6
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Apathy	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Depression	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Insomnia	1/56 (1.8%)	1	0/25 (0%)	0	2/20 (10%)	2
Reproductive system and breast disorders
Dysmenorrhoea	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Menstruation irregular	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Eczema	1/56 (1.8%)	1	0/25 (0%)	0	1/20 (5%)	1
Urticaria	0/56 (0%)	0	1/25 (4%)	1	0/20 (0%)	0
Vascular disorders
Orthostatic hypotension	0/56 (0%)	0	0/25 (0%)	0	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.