Trial Outcomes & Findings for Efficacy and Safety of Olanzapine in the Extended Treatment for Manic or Mixed Episode of Bipolar I Disorder (NCT NCT00266630)

NCT ID: NCT00266630

Last Updated: 2010-12-28

Results Overview

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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 139 participants
• Primary outcome timeframe: baseline through 18 weeks
• Results posted on: 2010-12-28

Participant Flow

Participant milestones

Measure	Olanzapine Monotherapy Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Overall Study STARTED	100	39
Overall Study COMPLETED	58	11
Overall Study NOT COMPLETED	42	28

Reasons for withdrawal

Measure	Olanzapine Monotherapy Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Overall Study Adverse Event	8	6
Overall Study Lack of Efficacy	1	4
Overall Study Entry Criteria not met	1	0
Overall Study Protocol Violation	1	3
Overall Study Physician Decision	1	2
Overall Study Withdrawal by Subject	10	2
Overall Study Lost to Follow-up	1	0
Overall Study Other	19	11

Baseline Characteristics

Efficacy and Safety of Olanzapine in the Extended Treatment for Manic or Mixed Episode of Bipolar I Disorder

Baseline characteristics by cohort

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.	Total n=139 Participants Total of all reporting groups
Age Continuous	41.8 years STANDARD_DEVIATION 11.7 • n=5 Participants	43.2 years STANDARD_DEVIATION 11.1 • n=7 Participants	42.2 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	21 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	18 Participants n=7 Participants	59 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	100 participants n=5 Participants	39 participants n=7 Participants	139 participants n=5 Participants
Region of Enrollment Japan	100 participants n=5 Participants	39 participants n=7 Participants	139 participants n=5 Participants
Current Episode - Mixed or Manic Manic	88 participants n=5 Participants	39 participants n=7 Participants	127 participants n=5 Participants
Current Episode - Mixed or Manic Mixed	12 participants n=5 Participants	0 participants n=7 Participants	12 participants n=5 Participants
Current Episode - Psychotic or Nonpsychotic Psychotic	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants
Current Episode - Psychotic or Nonpsychotic Nonpsychotic	87 participants n=5 Participants	30 participants n=7 Participants	117 participants n=5 Participants
Rapid Cyclers Rapid Cyclers	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants
Rapid Cyclers Non-Rapid Cyclers	93 participants n=5 Participants	36 participants n=7 Participants	129 participants n=5 Participants
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) overall	1.9 units on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	4.7 units on a scale STANDARD_DEVIATION 0.8 • n=7 Participants	2.7 units on a scale STANDARD_DEVIATION 1.6 • n=5 Participants
Hamilton Depression Scale - 17 item version (HAMD-17) Total Score	1.8 units on a scale STANDARD_DEVIATION 3.1 • n=5 Participants	4.4 units on a scale STANDARD_DEVIATION 3.9 • n=7 Participants	2.5 units on a scale STANDARD_DEVIATION 3.5 • n=5 Participants
Length of Current Episode	33.5 days STANDARD_DEVIATION 23.9 • n=5 Participants	35.0 days STANDARD_DEVIATION 26.7 • n=7 Participants	33.9 days STANDARD_DEVIATION 24.6 • n=5 Participants
Mean Age at Onset of Illness	31.5 years STANDARD_DEVIATION 11.6 • n=5 Participants	29.8 years STANDARD_DEVIATION 8.4 • n=7 Participants	31.0 years STANDARD_DEVIATION 10.8 • n=5 Participants
Young Mania Rating Scale (YMRS) Total Score	5.7 units on a scale STANDARD_DEVIATION 6.4 • n=5 Participants	33.2 units on a scale STANDARD_DEVIATION 6.6 • n=7 Participants	13.4 units on a scale STANDARD_DEVIATION 13.9 • n=5 Participants

PRIMARY outcome

Timeframe: baseline through 18 weeks

Population: The primary objective was only interested in the effects in the olanzapine monotherapy arm, thus the results for the olanzapine + mood stabilizer arm are presented as secondary outcomes. Analyzed were all participants in the olanzapine monotherapy arm who had baseline and post-baseline measurements. Last observation carried forward.

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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Scores - Olanzapine Monotherapy Arm Only	-3.0 units on a scale Standard Deviation 5.6	—

PRIMARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants in the olanzapine monotherapy arm who had baseline and post-baseline measurements. Last observation carried forward.

Defined by a 50% or more reduction in YMRS total score from baseline in Study BMAC to endpoint. 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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Response of Manic Symptoms - Olanzapine Monotherapy Arm Only	97 participants	—

PRIMARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants in the olanzapine monotherapy arm who had baseline and post-baseline measurements. Last observation carried forward.

Remission of Mania was defined as a YMRS total score of less than or equal to 12 at endpoint. 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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Remission of Mania - Olanzapine Monotherapy Arm Only	93 participants	—

PRIMARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants in the olanzapine monotherapy group who were in remission at baseline (end of Study BMAC) with 12 points or less in YMRS total score and 7 points or less in the 17-item Hamilton Depression Rating Scale total score.

Patients achieved remission in Study BMAC (defined as YMRS total score <=12 and HAMD-17 total score <=7) and obtained YMRS total score of >=15 at any time during Study BMEX. 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. The primary objective was only interested in the effects in the olanzapine monotherapy arm.

Outcome measures

Measure	Olanzapine Monotherapy n=79 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Relapse of Manic Symptoms - Olanzapine Monotherapy Arm Only	3 participants	—

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants who had baseline and post-baseline measurements. Last observation carried forward.

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

Measure	Olanzapine Monotherapy n=39 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Change From Baseline to Endpoint on the YMRS Total Score - Olanzapine + Mood Stabilizer Only	-19.8 units on a scale Standard Deviation 17.8	—

SECONDARY outcome

Timeframe: baseline, Weeks 1, 2, 4, 6, 10, 14, 18

Population: Analyzed were all participants who had baseline and post-baseline measurements. Last observation carried forward.

Measures severity of the patient's overall severity of bipolar symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data baseline	1.9 units on a scale Standard Deviation 1.0	4.7 units on a scale Standard Deviation 0.8
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data 1 week	1.8 units on a scale Standard Deviation 1.0	4.1 units on a scale Standard Deviation 1.2
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data 2 weeks	1.8 units on a scale Standard Deviation 1.0	3.7 units on a scale Standard Deviation 1.3
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data 4 weeks	1.7 units on a scale Standard Deviation 1.0	3.5 units on a scale Standard Deviation 1.6
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data 6 weeks	1.7 units on a scale Standard Deviation 1.1	3.4 units on a scale Standard Deviation 1.7
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data 10 weeks	1.7 units on a scale Standard Deviation 1.1	3.0 units on a scale Standard Deviation 1.8
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data 14 weeks	1.8 units on a scale Standard Deviation 1.2	3.0 units on a scale Standard Deviation 1.9
Clinical Global Impressions - Bipolar Version, Severity of Illness (CGI-BP) Overall, Visit Data 18 weeks endpoint	1.7 units on a scale Standard Deviation 1.2	2.9 units on a scale Standard Deviation 2.0

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants who had equal to or less than 7 points on the HAMD-17 total score at baseline.

Incidence of depressive symptoms was defined as a score of equal to or more than 13 points on the HAMD-17. The 17-item HAMD measures depression severity. Each item was evaluated and scored a 3-point scale (e.g. absent, mild, marked) or a 5-point scale (e.g. absent, mild, moderate, severe, very severe). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).

Outcome measures

Measure	Olanzapine Monotherapy n=92 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=30 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants Who Experienced Switch to Symptomatic Depression as Measured by the Hamilton Depression Scale - 17 Item Version (HAMD-17)	4 participants	1 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants in the olanzapine monotherapy group who had 12 points or less in the YMRS total score and 7 points or less in the HAMD-17 total score at baseline.

Assessed were participants meeting remission criteria for bipolar disorder in Study BMAC and have a HAMD-17 total score greater than or equal to 13 at any time. The 17-item HAMD measures depression severity. Each item was evaluated and scored using a 3-point scale (e.g. absent, mild, marked) or a 5-point scale (e.g. absent, mild, moderate, severe, very severe). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).

Outcome measures

Measure	Olanzapine Monotherapy n=79 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Relapse of Depressive Symptoms	4 participants	—

SECONDARY outcome

Timeframe: Week 18

Population: Analyzed were all participants who had baseline and post-baseline measurements. Last observation carried forward.

Participants who had equal to or less than 12 points in YMRS total score and equal to or less than 7 points in HAMD-17 total score at 18 weeks. YMRS: 11-item scale, measures the severity of manic episodes. 4 items are rated from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total: 0 to 60. The 17-item HAMD measures depression severity. Each item was evaluated and scored using a 3-point scale or a 5-point scale. HAMD-17 total score: 0 (normal) to 52 (severe).

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants Who Experienced Remission of Bipolar Disorder	54 participants	12 participants

SECONDARY outcome

Timeframe: baseline, Weeks 1, 2, 4, 6, 10, 14, 18

Population: Analyzed were all participants who had baseline and post-baseline measurements. Last observation carried forward.

Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale. 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 the analysis, the score was converted to 0 to 6 for each item range; hence, the total score ranges from 0 to 42.

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Positive and Negative Syndrome Scale Positive Scores - Visit Data 6 weeks	7.3 units on a scale Standard Deviation 1.2	10.1 units on a scale Standard Deviation 5.4
Positive and Negative Syndrome Scale Positive Scores - Visit Data baseline	7.7 units on a scale Standard Deviation 1.8	12.5 units on a scale Standard Deviation 5.7
Positive and Negative Syndrome Scale Positive Scores - Visit Data 1 week	7.5 units on a scale Standard Deviation 1.6	10.5 units on a scale Standard Deviation 4.1
Positive and Negative Syndrome Scale Positive Scores - Visit Data 2 weeks	7.5 units on a scale Standard Deviation 1.4	10.1 units on a scale Standard Deviation 3.9
Positive and Negative Syndrome Scale Positive Scores - Visit Data 4 weeks	7.4 units on a scale Standard Deviation 1.4	10.1 units on a scale Standard Deviation 5.4
Positive and Negative Syndrome Scale Positive Scores - Visit Data 10 weeks	7.4 units on a scale Standard Deviation 1.7	9.9 units on a scale Standard Deviation 5.4
Positive and Negative Syndrome Scale Positive Scores - Visit Data 14 weeks	7.4 units on a scale Standard Deviation 1.7	9.9 units on a scale Standard Deviation 5.4
Positive and Negative Syndrome Scale Positive Scores - Visit Data 18 week endpoint	7.4 units on a scale Standard Deviation 1.7	9.9 units on a scale Standard Deviation 5.4

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants who had a manic episode at baseline.

As defined as a shift from a Manic Episode at baseline to a Major Depressive Episode, at any post baseline visit, based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision.

Outcome measures

Measure	Olanzapine Monotherapy n=88 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants Who Switched to Syndromic Depression	8 participants	4 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants who had baseline and post-baseline measurements. Last observation carried forward.

A scale used to assess the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). The items for the assessment of individual symptoms are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Parkinsonism is assessed by the total points of items 1 to 5; akathisia, dystonia and dyskinesia are assessed by the points given to the corresponding items.

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Maximum Change From Baseline to Endpoint on the Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) - Total Score Baseline	0.35 units on a scale Standard Deviation 1.01	0.18 units on a scale Standard Deviation 0.60
Maximum Change From Baseline to Endpoint on the Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) - Total Score Maximum Change from baseline to endpoint	0.05 units on a scale Standard Deviation 1.21	0.64 units on a scale Standard Deviation 1.51

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Included were all participants who did not have an abnormal value at baseline.

DIEPSS assesses the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). Parkinsonism is assessed by the total points of items 1 to 5 (total score of 0 to 20). Treatment-emergent parkinsonism was defined as a score of equal or greater than 3 on 1 item, equal or greater than 2 on 2 items, or an increase of equal or greater than 3 from baseline on the parkinsonism total.

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Treatment-Emergent Parkinsonism Based on DIEPSS Scores	1 participants	3 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Included were all participants who did not have an abnormal value at baseline.

DIEPSS assesses the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). The items are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Treatment-emergent akathisia was defined as a score of equal or more than 2 or an increase of equal or more than 2 points from baseline on the akathisia item (total score possible 0 to 4 points).

Outcome measures

Measure	Olanzapine Monotherapy n=98 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=38 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Treatment-Emergent Akathisia Based on DIEPSS Scores	3 participants	2 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Included were all participants who did not have an abnormal value at baseline.

DIEPSS assesses the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). The items are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Treatment-emergent dystonia was defined as a score equal or more than 2 or an increase of equal or more than 2 points from baseline on the dystonia item (total score possible 0 to 4 points).

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=38 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Treatment-Emergent Dystonia Based on DIEPSS Scores	0 participants	1 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Included were all participants who did not have an abnormal value at baseline.

DIEPSS assesses the extrapyramidal symptoms attributable to antipsychotics. Consists of 9 items (8 to assess individual symptoms and 1 to assess global severity). Each item is assessed from 0 (none, normal) to 4 (severe). The total points of 8 items are defined as DIEPSS total (0 to 32 points). The items are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Treatment-emergent dyskenisia was defined as a score of equal or more than 2 or an increase of equal to or more than 2 points from baseline on the dyskenisia item (total score possible 0 to 4 points).

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Treatment-Emergent Dyskenisia Based on DIEPSS Scores	0 participants	0 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants without an abnormal value in the direction at baseline (for example, participants with an abnormally low value at baseline who experienced an abnormally low value at any time post baseline were not included, but were included if they experienced an abnormally high value at any time post baseline).

Triglycerides: high limit equal to or more than 500 milligram/deciliter (mg/dL); Glucose (non-fasting): low limit 2.4975 mmol/liter (L); high limit 13.875 mmol/L; Glucose (fasting): low limit 2.4975 mmol/L; high limit 6.993 mmol/L.

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=38 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Potentially Clinically Significant Changes in Laboratory Analytes High triglycerides; n=100, n=38	5 participants	2 participants
Number of Participants With Potentially Clinically Significant Changes in Laboratory Analytes Low glucose (non-fasting); n=64, n=28	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Changes in Laboratory Analytes High glucose (non-fasting); n=64, n=28	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Changes in Laboratory Analytes Low glucose (fasting); n=40, n=6	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Changes in Laboratory Analytes High glucose (fasting); n=40, n=6	3 participants	0 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all study participants.

Low systolic blood pressure (SBP): <=90 millimeter mercury (mmHg) and decrease of >=20 mmHg; High SBP: >=180 mmHg and increase of >=20 mmHg; Low diastolic blood pressure (DBP): <=50 mmHg and decrease of >=15 mmHg; High DBP: >=105 mmHg and increase of >=15 mmHg; Low pulse: <50 beats per minute (bpm) and decrease of >=15 bpm; High pulse: >120 bpm and an increase of >=15 bpm; Low weight: decrease of >=7%; High weight: increase of >=7%;

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight Low systolic blood pressure	6 participants	2 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight High systolic blood pressure	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight Low diastolic blood pressure	4 participants	1 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight High diastolic blood pressure	1 participants	0 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight Low weight	3 participants	1 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight High weight	17 participants	10 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight Low pulse	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Changes in Vital Signs and Weight High pulse	0 participants	0 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants who had baseline and post-baseline measurements and no abnormal values in the direction at baseline (e.g. participants with an abnormally low value for a given parameter at baseline who showed an abnormally low value for the same parameter at a later visit were not included). Last observation carried forward.

High QTcF: more than or equal to 450 milliseconds (msec) for males; more than or equal to 470 milliseconds (msec) for females

Outcome measures

Measure	Olanzapine Monotherapy n=97 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Potentially Clinically Significant Changes in Electrocardiograms - High Fridericia Corrected QT Interval (QTcF)	0 participants	0 participants

SECONDARY outcome

Timeframe: baseline through 18 weeks

Population: Analyzed were all participants who had baseline and post-baseline measurements. Last observation carried forward.

High density lipoprotein: males low 40 milligram/deciliter (mg/dL), high 80 mg/dL; females low 40 mg/dL, high 90 mg/dL. Low density lipoprotein (LDL): males and females low 70 mg/dL, high 139 mg/dL. Hemoglobin A1C (HBA1C): males and females low 4.3%, high 5.8%.

Outcome measures

Measure	Olanzapine Monotherapy n=100 Participants Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanzapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 Participants Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Number of Participants With Treatment-emergent Abnormal, High, or Low Laboratory Values Low high density lipoprotein (HDL); n=93, n=36	10 participants	3 participants
Number of Participants With Treatment-emergent Abnormal, High, or Low Laboratory Values High high density lipoprotein (HDL); n=95, n=37	5 participants	1 participants
Number of Participants With Treatment-emergent Abnormal, High, or Low Laboratory Values Low low density lipoprotein (LDL); n=97; n=37	1 participants	1 participants
Number of Participants With Treatment-emergent Abnormal, High, or Low Laboratory Values High low density lipoprotein (LDL); n=71, n=31	24 participants	11 participants
Number of Participants With Treatment-emergent Abnormal, High, or Low Laboratory Values Low hemoglobin A1C (HBA1C); n=100, n=39	1 participants	1 participants
Number of Participants With Treatment-emergent Abnormal, High, or Low Laboratory Values High hemoglobin A1C (HBA1C); n=97, n=38	2 participants	0 participants

Adverse Events

Olanzapine Monotherapy

Serious events: 1 serious events

Other events: 59 other events

Deaths: 0 deaths

Olanzapine + Mood Stabilizer

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	Olanzapine Monotherapy n=100 participants at risk Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 participants at risk Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Injury, poisoning and procedural complications Radius fracture	1.0% 1/100 • Number of events 1	0.00% 0/39

Other adverse events

Measure	Olanzapine Monotherapy n=100 participants at risk Olanzapine extension for Study BMAC patients who completed Visit 8. Patients received olanapine 5-20 mg for 18 weeks.	Olanzapine + Mood Stabilizer n=39 participants at risk Olanzapine extension for Study BMAC patients who discontinued at Visit 4 or 5. Patients received an initial dose of olanzapine 10 mg for 1 week and subsequent doses of olanzapine 5-20 mg for 17 weeks. Patients received one (1) mood stabilizer (lithium, valproate or carbamazepine) for 18 weeks.
Gastrointestinal disorders Constipation	3.0% 3/100 • Number of events 3	7.7% 3/39 • Number of events 3
General disorders Thirst	5.0% 5/100 • Number of events 5	5.1% 2/39 • Number of events 2
Infections and infestations Nasopharyngitis	17.0% 17/100 • Number of events 19	15.4% 6/39 • Number of events 6
Injury, poisoning and procedural complications Contusion	2.0% 2/100 • Number of events 3	5.1% 2/39 • Number of events 2
Injury, poisoning and procedural complications Fall	0.00% 0/100	5.1% 2/39 • Number of events 4
Investigations Alanine aminotransferase increased	2.0% 2/100 • Number of events 2	7.7% 3/39 • Number of events 3
Investigations Blood cholesterol increased	3.0% 3/100 • Number of events 3	7.7% 3/39 • Number of events 3
Investigations Blood triglycerides increased	5.0% 5/100 • Number of events 5	15.4% 6/39 • Number of events 6
Investigations Gamma-glutamyltransferase increased	0.00% 0/100	5.1% 2/39 • Number of events 2
Investigations Low density lipoprotein increased	1.0% 1/100 • Number of events 1	5.1% 2/39 • Number of events 2
Investigations Weight increased	9.0% 9/100 • Number of events 9	12.8% 5/39 • Number of events 5
Nervous system disorders Somnolence	15.0% 15/100 • Number of events 15	17.9% 7/39 • Number of events 8
Psychiatric disorders Depressive symptom	7.0% 7/100 • Number of events 7	5.1% 2/39 • Number of events 2
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/100	5.1% 2/39 • Number of events 2

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60