Trial Outcomes & Findings for Olanzapine Treatment of Patients With Bipolar I Disorder (NCT NCT00510146)
NCT ID: NCT00510146
Last Updated: 2011-05-26
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
514 participants
Primary outcome timeframe
Baseline, Endpoint (Week 6)
Results posted on
2011-05-26
Participant Flow
Study Period I (2-28 days) included screening and lead-in period for discontinuation of excluded medications at least 25 hours before day of randomization. Study Period II was 6-week, double-blind (Acute Phase) of treatment. Study Period III was 18-week, open-label extension for those who completed Study Period II.
Participant milestones
| Measure |
Olanzapine
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Double-Blind Treatment
STARTED
|
343
|
171
|
|
Double-Blind Treatment
COMPLETED
|
267
|
122
|
|
Double-Blind Treatment
NOT COMPLETED
|
76
|
49
|
|
Open-Label Treatment
STARTED
|
267
|
122
|
|
Open-Label Treatment
COMPLETED
|
196
|
96
|
|
Open-Label Treatment
NOT COMPLETED
|
71
|
26
|
Reasons for withdrawal
| Measure |
Olanzapine
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Double-Blind Treatment
Adverse Event
|
30
|
13
|
|
Double-Blind Treatment
Lack of Efficacy
|
6
|
13
|
|
Double-Blind Treatment
Lost to Follow-up
|
3
|
7
|
|
Double-Blind Treatment
Physician Decision
|
6
|
0
|
|
Double-Blind Treatment
Protocol Violation
|
1
|
2
|
|
Double-Blind Treatment
Withdrawal by Subject
|
27
|
13
|
|
Double-Blind Treatment
Clinical Relapse
|
0
|
1
|
|
Double-Blind Treatment
Entry Criteria Not Met
|
3
|
0
|
|
Open-Label Treatment
Adverse Event
|
22
|
8
|
|
Open-Label Treatment
Death
|
1
|
1
|
|
Open-Label Treatment
Lack of Efficacy
|
4
|
0
|
|
Open-Label Treatment
Lost to Follow-up
|
10
|
1
|
|
Open-Label Treatment
Physician Decision
|
3
|
1
|
|
Open-Label Treatment
Protocol Violation
|
4
|
2
|
|
Open-Label Treatment
Withdrawal by Subject
|
24
|
12
|
|
Open-Label Treatment
Clinical Relapse
|
1
|
1
|
|
Open-Label Treatment
Sponsor Decision
|
2
|
0
|
Baseline Characteristics
Olanzapine Treatment of Patients With Bipolar I Disorder
Baseline characteristics by cohort
| Measure |
Olanzapine
n=343 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=171 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
Total
n=514 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
35.93 years
STANDARD_DEVIATION 11.13 • n=99 Participants
|
34.96 years
STANDARD_DEVIATION 11.02 • n=107 Participants
|
35.61 years
STANDARD_DEVIATION 11.09 • n=206 Participants
|
|
Sex: Female, Male
Female
|
205 Participants
n=99 Participants
|
95 Participants
n=107 Participants
|
300 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
138 Participants
n=99 Participants
|
76 Participants
n=107 Participants
|
214 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
36 participants
n=99 Participants
|
22 participants
n=107 Participants
|
58 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
African
|
18 participants
n=99 Participants
|
4 participants
n=107 Participants
|
22 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
6 participants
n=99 Participants
|
3 participants
n=107 Participants
|
9 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
282 participants
n=99 Participants
|
141 participants
n=107 Participants
|
423 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Native American
|
1 participants
n=99 Participants
|
1 participants
n=107 Participants
|
2 participants
n=206 Participants
|
|
Region of Enrollment
China
|
140 participants
n=99 Participants
|
70 participants
n=107 Participants
|
210 participants
n=206 Participants
|
|
Region of Enrollment
Japan
|
104 participants
n=99 Participants
|
52 participants
n=107 Participants
|
156 participants
n=206 Participants
|
|
Region of Enrollment
Korea, Republic of
|
20 participants
n=99 Participants
|
10 participants
n=107 Participants
|
30 participants
n=206 Participants
|
|
Region of Enrollment
Taiwan
|
19 participants
n=99 Participants
|
9 participants
n=107 Participants
|
28 participants
n=206 Participants
|
|
Region of Enrollment
United States
|
60 participants
n=99 Participants
|
30 participants
n=107 Participants
|
90 participants
n=206 Participants
|
|
Age at onset, Bipolar I Disorder
|
27.57 years
STANDARD_DEVIATION 10.98 • n=99 Participants
|
26.12 years
STANDARD_DEVIATION 9.90 • n=107 Participants
|
27.09 years
STANDARD_DEVIATION 10.64 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Intention-to-treat population (ITT) with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF)
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).
Outcome measures
| Measure |
Olanzapine
n=339 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)
Baseline
|
29.36 units on a scale
Standard Deviation 5.71
|
28.69 units on a scale
Standard Deviation 6.33
|
|
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)
Change
|
-14.26 units on a scale
Standard Deviation 9.73
|
-11.71 units on a scale
Standard Deviation 11.09
|
SECONDARY outcome
Timeframe: Endpoint (Week 6)Population: Intention-to-treat (ITT) population; all randomized participants.
Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score. 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).
Outcome measures
| Measure |
Olanzapine
n=343 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=171 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase)
|
52.5 percentage of participants
|
43.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through Endpoint (Week 6)Population: Intention-to-treat (ITT) population; all randomized participants.
Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. 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).
Outcome measures
| Measure |
Olanzapine
n=343 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=171 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase)
|
53.9 percentage of participants
|
49.7 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Intention-to-treat population (ITT) with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF)
CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The score ranges from 1 (normal, not ill) to 7 (very seriously ill).
Outcome measures
| Measure |
Olanzapine
n=339 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
Baseline-Mania
|
1.07 units on a scale
Standard Deviation 0.29
|
1.11 units on a scale
Standard Deviation 0.35
|
|
Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
Change-Mania
|
0.00 units on a scale
Standard Deviation 0.43
|
0.09 units on a scale
Standard Deviation 0.59
|
|
Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
Baseline-Depression
|
4.54 units on a scale
Standard Deviation 0.73
|
4.53 units on a scale
Standard Deviation 0.73
|
|
Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
Change-Depression
|
-1.45 units on a scale
Standard Deviation 1.26
|
-1.20 units on a scale
Standard Deviation 1.36
|
|
Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
Baseline- Overall
|
4.45 units on a scale
Standard Deviation 0.79
|
4.44 units on a scale
Standard Deviation 0.79
|
|
Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)
Change- Overall
|
-1.40 units on a scale
Standard Deviation 1.28
|
-1.08 units on a scale
Standard Deviation 1.27
|
SECONDARY outcome
Timeframe: Baseline through Endpoint (Week 6 )Population: Intention-to-treat (ITT) population; all randomized participants.
Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. 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).
Outcome measures
| Measure |
Olanzapine
n=343 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=171 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Recovery (Acute Phase)
|
13.7 percentage of participants
|
9.4 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Intention-to-treat population (ITT) with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF)
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
n=339 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase)
Baseline
|
2.14 units on a scale
Standard Deviation 2.10
|
1.95 units on a scale
Standard Deviation 2.18
|
|
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase)
Change
|
-0.78 units on a scale
Standard Deviation 2.56
|
0.31 units on a scale
Standard Deviation 4.21
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Intention-to-treat population (ITT) with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF)
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).
Outcome measures
| Measure |
Olanzapine
n=318 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=155 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)
Baseline
|
22.62 units on a scale
Standard Deviation 3.47
|
22.35 units on a scale
Standard Deviation 3.53
|
|
Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)
Change
|
-11.44 units on a scale
Standard Deviation 7.02
|
-9.12 units on a scale
Standard Deviation 7.99
|
SECONDARY outcome
Timeframe: Endpoint (Week 6)Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
In the MINI Major Depressive Episode module, participants are asked a series of Yes/No questions to determine whether or not they are experiencing a major depressive episode or a major depressive episode with melancholic features.
Outcome measures
| Measure |
Olanzapine
n=339 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase)
Major Depressive Episode
|
55.5 percentage of participants
|
60.4 percentage of participants
|
|
Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase)
Major Depressive Episode with Melancholic Features
|
77.8 percentage of participants
|
74.1 percentage of participants
|
SECONDARY outcome
Timeframe: Endpoint (Week 6)Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
In the MINI Manic Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing hypomanic or manic episodes.
Outcome measures
| Measure |
Olanzapine
n=332 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase)
|
2.1 percentage of participants
|
0.6 percentage of participants
|
SECONDARY outcome
Timeframe: Endpoint (Week 6)Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
In the MINI Psychotic Features Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing mood disorder with psychotic features or current psychotic disorders.
Outcome measures
| Measure |
Olanzapine
n=339 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase)
Mood Disorder with Psychotic Features
|
3.6 percentage of participants
|
2.4 percentage of participants
|
|
Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase)
Psychotic Disorders
|
0.0 percentage of participants
|
0.6 percentage of participants
|
SECONDARY outcome
Timeframe: Endpoint (Week 6)Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
In the MINI Alcohol Abuse and Dependence Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current alcohol dependence or abuse.
Outcome measures
| Measure |
Olanzapine
n=335 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)
Dependence
|
0.6 percentage of participants
|
0.6 percentage of participants
|
|
Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)
Abuse
|
0.6 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Endpoint (Week 6)Population: Intention-to-treat (ITT) population with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
In the MINI Substance Dependence and Abuse Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current non-alcohol substance use dependence or abuse.
Outcome measures
| Measure |
Olanzapine
n=335 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase)
Dependence
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase)
Abuse
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through Endpoint (Week 6)Population: Intention-to-treat (ITT) population
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.
Outcome measures
| Measure |
Olanzapine
n=343 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=171 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Emergence of Mania During the Study (Acute Phase)
|
0.6 percentage of participants
|
2.9 percentage of participants
|
SECONDARY outcome
Timeframe: Endpoint (Week 6)Population: Participants with a normal baseline and an endpoint result.
EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not \>=3 on 1 item nor \>=2 on 2 items; abnormal endpoint is defined as a score \>=3 on 1 item or \>=2 on 2 items, or an increase of 3 on Parkinsonism total. 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.
Outcome measures
| Measure |
Olanzapine
n=337 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)
Akathisia (N=335, 169)
|
2.7 percentage of participants
|
1.2 percentage of participants
|
|
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)
Dyskinesia (N=337, 169)
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)
Dystonia (N=337, 169)
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)
Parkinsonism (N=337, 169)
|
0.9 percentage of participants
|
0.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=320 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=159 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Baseline- Standing Systolic (N=320, 159)
|
112.39 mmHg (millimeters of mercury)
Standard Deviation 13.25
|
115.65 mmHg (millimeters of mercury)
Standard Deviation 14.39
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Change- Standing Systolic (N=320, 159)
|
-0.99 mmHg (millimeters of mercury)
Standard Deviation 10.83
|
-0.67 mmHg (millimeters of mercury)
Standard Deviation 11.18
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Baseline- Sitting Systolic (N=340, 169)
|
112.35 mmHg (millimeters of mercury)
Standard Deviation 13.42
|
114.39 mmHg (millimeters of mercury)
Standard Deviation 13.67
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Change- Sitting Systolic (N=340, 169)
|
-0.36 mmHg (millimeters of mercury)
Standard Deviation 11.10
|
0.04 mmHg (millimeters of mercury)
Standard Deviation 12.16
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Baseline- Standing Diastolic (N=320, 159)
|
74.77 mmHg (millimeters of mercury)
Standard Deviation 10.20
|
76.87 mmHg (millimeters of mercury)
Standard Deviation 10.26
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Change- Standing Diastolic (N=320, 159)
|
-0.48 mmHg (millimeters of mercury)
Standard Deviation 8.71
|
-0.14 mmHg (millimeters of mercury)
Standard Deviation 8.44
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Baseline- Sitting Diastolic (N=340, 169)
|
73.07 mmHg (millimeters of mercury)
Standard Deviation 9.93
|
73.92 mmHg (millimeters of mercury)
Standard Deviation 9.86
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Change- Sitting Diastolic (N=340, 169)
|
-0.11 mmHg (millimeters of mercury)
Standard Deviation 9.37
|
0.39 mmHg (millimeters of mercury)
Standard Deviation 9.08
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Baseline- Orthostatic Change-Systolic (N=320, 159)
|
0.54 mmHg (millimeters of mercury)
Standard Deviation 6.51
|
1.21 mmHg (millimeters of mercury)
Standard Deviation 7.67
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Change- Orthostatic Change-Systolic (N=320, 159)
|
-0.65 mmHg (millimeters of mercury)
Standard Deviation 8.20
|
-0.45 mmHg (millimeters of mercury)
Standard Deviation 11.45
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Baseline- Orthostatic Change-Diastolic (N=320, 159
|
1.92 mmHg (millimeters of mercury)
Standard Deviation 5.93
|
2.96 mmHg (millimeters of mercury)
Standard Deviation 5.57
|
|
Change From Baseline to Endpoint in Blood Pressure (Acute Phase)
Change- Orthostatic Change-Diastolic (N=320, 159)
|
-0.52 mmHg (millimeters of mercury)
Standard Deviation 6.79
|
-0.47 mmHg (millimeters of mercury)
Standard Deviation 6.78
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=340 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Weight (Acute Phase)
Baseline
|
66.11 kilograms
Standard Deviation 18.11
|
68.30 kilograms
Standard Deviation 18.73
|
|
Change From Baseline to Endpoint in Weight (Acute Phase)
Endpoint
|
2.45 kilograms
Standard Deviation 2.82
|
-0.13 kilograms
Standard Deviation 2.10
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=329 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=160 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Baseline- Fasting Glucose (N=320, 155)
|
5.11 millimole/Liter
Standard Deviation 0.58
|
5.12 millimole/Liter
Standard Deviation 0.57
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Change- Fasting Glucose (N=320, 155)
|
0.10 millimole/Liter
Standard Deviation 0.61
|
0.02 millimole/Liter
Standard Deviation 0.54
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Baseline- Cholesterol (N=329, 160)
|
4.83 millimole/Liter
Standard Deviation 1.01
|
4.81 millimole/Liter
Standard Deviation 1.00
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Change- Cholesterol (N=329, 160)
|
0.24 millimole/Liter
Standard Deviation 0.76
|
-0.07 millimole/Liter
Standard Deviation 0.49
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Baseline-Triglycerides (N=329, 160)
|
1.39 millimole/Liter
Standard Deviation 0.85
|
1.34 millimole/Liter
Standard Deviation 0.80
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Change- Triglycerides (N=329, 160)
|
0.26 millimole/Liter
Standard Deviation 0.97
|
0.03 millimole/Liter
Standard Deviation 0.71
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Baseline- LDL Cholesterol (N=328, 159)
|
2.77 millimole/Liter
Standard Deviation 0.87
|
2.83 millimole/Liter
Standard Deviation 0.84
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Change- LDL Cholesterol (N=328, 159)
|
0.17 millimole/Liter
Standard Deviation 0.66
|
-0.09 millimole/Liter
Standard Deviation 0.48
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Baseline- HDL Cholesterol (N=329, 160)
|
1.43 millimole/Liter
Standard Deviation 0.41
|
1.36 millimole/Liter
Standard Deviation 0.35
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)
Change- HDL Cholesterol (N=329, 160)
|
-0.03 millimole/Liter
Standard Deviation 0.25
|
0.02 millimole/Liter
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=329 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=160 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Albumin (Acute Phase)
Baseline
|
43.07 gram/Liter
Standard Deviation 3.85
|
43.47 gram/Liter
Standard Deviation 3.69
|
|
Change From Baseline to Endpoint in Albumin (Acute Phase)
Change
|
-0.81 gram/Liter
Standard Deviation 2.89
|
0.03 gram/Liter
Standard Deviation 3.11
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=329 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=160 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT)
Baseline (ALT/SGPT)
|
21.68 units/Liter
Standard Deviation 16.53
|
21.18 units/Liter
Standard Deviation 13.17
|
|
Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT)
Change (ALT/SGPT)
|
8.34 units/Liter
Standard Deviation 26.90
|
0.00 units/Liter
Standard Deviation 13.63
|
|
Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT)
Baseline (AST/SGOT)
|
21.61 units/Liter
Standard Deviation 8.34
|
20.25 units/Liter
Standard Deviation 6.70
|
|
Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT)
Change (AST/SGOT)
|
4.31 units/Liter
Standard Deviation 15.66
|
1.26 units/Liter
Standard Deviation 11.06
|
|
Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT)
Baseline (GGT)
|
24.87 units/Liter
Standard Deviation 36.59
|
23.63 units/Liter
Standard Deviation 23.17
|
|
Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT)
Change (GGT)
|
5.36 units/Liter
Standard Deviation 22.70
|
-1.21 units/Liter
Standard Deviation 11.67
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=329 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=160 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Baseline- Direct Bilirubin
|
2.45 micromole/Liter
Standard Deviation 1.23
|
2.40 micromole/Liter
Standard Deviation 1.08
|
|
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Change- Direct Bilirubin
|
-0.21 micromole/Liter
Standard Deviation 1.03
|
0.12 micromole/Liter
Standard Deviation 1.02
|
|
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Baseline- Total Bilirubin
|
9.74 micromole/Liter
Standard Deviation 5.18
|
9.42 micromole/Liter
Standard Deviation 4.58
|
|
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Change- Total Bilirubin
|
-0.68 micromole/Liter
Standard Deviation 4.57
|
0.47 micromole/Liter
Standard Deviation 4.27
|
|
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Baseline- Uric Acid
|
307.19 micromole/Liter
Standard Deviation 92.03
|
314.38 micromole/Liter
Standard Deviation 86.69
|
|
Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)
Change- Uric Acid
|
19.55 micromole/Liter
Standard Deviation 51.10
|
-1.86 micromole/Liter
Standard Deviation 50.37
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=328 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=158 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)
Baseline
|
4.65 trillion cells per liter ( TRIL/L)
Standard Deviation 0.51
|
4.71 trillion cells per liter ( TRIL/L)
Standard Deviation 0.52
|
|
Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)
Change
|
-0.05 trillion cells per liter ( TRIL/L)
Standard Deviation 0.27
|
0.02 trillion cells per liter ( TRIL/L)
Standard Deviation 0.27
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=328 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=158 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Hematocrit (Acute Phase)
Baseline
|
0.42 proportion of blood volume
Standard Deviation 0.04
|
0.43 proportion of blood volume
Standard Deviation 0.05
|
|
Change From Baseline to Endpoint in Hematocrit (Acute Phase)
Change
|
-0.01 proportion of blood volume
Standard Deviation 0.03
|
0.00 proportion of blood volume
Standard Deviation 0.03
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=312 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=146 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)
Baseline
|
5.34 percent of glycosylated hemoglobin
Standard Deviation 0.37
|
5.37 percent of glycosylated hemoglobin
Standard Deviation 0.37
|
|
Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)
Change
|
0.04 percent of glycosylated hemoglobin
Standard Deviation 0.26
|
-0.03 percent of glycosylated hemoglobin
Standard Deviation 0.28
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=328 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=158 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Hemoglobin (Acute Phase)
Baseline
|
8.65 millimole/Liter of iron (Fe)
Standard Deviation 0.99
|
8.73 millimole/Liter of iron (Fe)
Standard Deviation 0.97
|
|
Change From Baseline to Endpoint in Hemoglobin (Acute Phase)
Change
|
-0.11 millimole/Liter of iron (Fe)
Standard Deviation 0.50
|
0.05 millimole/Liter of iron (Fe)
Standard Deviation 0.50
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=318 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=147 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Prolactin (Acute Phase)
Baseline
|
15.40 microgram/Liter
Standard Deviation 16.89
|
15.86 microgram/Liter
Standard Deviation 21.54
|
|
Change From Baseline to Endpoint in Prolactin (Acute Phase)
Change
|
12.07 microgram/Liter
Standard Deviation 24.00
|
-1.18 microgram/Liter
Standard Deviation 26.49
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=314 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=148 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)
Baseline
|
1.02 ratio
Standard Deviation 0.01
|
1.02 ratio
Standard Deviation 0.01
|
|
Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)
Change
|
-0.00 ratio
Standard Deviation 0.01
|
0.00 ratio
Standard Deviation 0.01
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval).
Outcome measures
| Measure |
Olanzapine
n=295 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=145 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
Baseline- QTcB
|
415.79 milliseconds
Standard Deviation 20.55
|
418.42 milliseconds
Standard Deviation 19.95
|
|
Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
Baseline- QTcF
|
406.85 milliseconds
Standard Deviation 19.53
|
408.10 milliseconds
Standard Deviation 18.72
|
|
Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
Change- QTcF
|
2.82 milliseconds
Standard Deviation 14.21
|
0.50 milliseconds
Standard Deviation 12.27
|
|
Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)
Change- QTcB
|
6.58 milliseconds
Standard Deviation 18.01
|
1.21 milliseconds
Standard Deviation 16.02
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=309 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=148 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Heart Rate (Acute Phase)
Baseline
|
69.63 beats per minute (bpm)
Standard Deviation 12.65
|
70.51 beats per minute (bpm)
Standard Deviation 11.94
|
|
Change From Baseline to Endpoint in Heart Rate (Acute Phase)
Change
|
3.49 beats per minute (bpm)
Standard Deviation 11.18
|
0.87 beats per minute (bpm)
Standard Deviation 11.51
|
SECONDARY outcome
Timeframe: Baseline, Endpoint (Week 6)Population: Safety population; participants with non-missing baseline value and at least one non-missing post baseline value, last observation carried forward (LOCF).
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.
Outcome measures
| Measure |
Olanzapine
n=337 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=169 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)
Baseline
|
2.09 units on a scale
Standard Deviation 3.44
|
2.40 units on a scale
Standard Deviation 3.49
|
|
Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)
Change
|
-0.42 units on a scale
Standard Deviation 3.71
|
-0.59 units on a scale
Standard Deviation 3.44
|
SECONDARY outcome
Timeframe: Baseline through Week 6 (Acute Phase)Population: All enrolled participants in Acute Phase
Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events.
Outcome measures
| Measure |
Olanzapine
n=343 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
n=171 Participants
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Number of Participants With Adverse Events (Acute Phase)
Serious
|
6 participants
|
7 participants
|
|
Number of Participants With Adverse Events (Acute Phase)
Non-Serious
|
238 participants
|
88 participants
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)Population: Total participants in the open-label extension phase.
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). Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score.
Outcome measures
| Measure |
Olanzapine
n=389 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase)
|
43.7 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)Population: Total participants in open-label extension phase.
Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. 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).
Outcome measures
| Measure |
Olanzapine
n=389 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase)
|
85.1 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)Population: Total participants in open-label extension phase.
Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. 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).
Outcome measures
| Measure |
Olanzapine
n=389 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Recovery (Open-Label Phase)
|
69.9 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
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
n=385 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase)
Baseline
|
1.11 units on a scale
Standard Deviation 2.87
|
—
|
|
Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase)
Change
|
-0.03 units on a scale
Standard Deviation 2.55
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)Population: Total participants in the open-label extension phase.
Emergence of mania is defined as first occurrence of score of \>=15 in the YMRS total score in the Open-Label Extension. 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
n=389 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase)
|
0.8 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Endpoint (Week 24)Population: Participants who entered Open-Label Phase with a normal baseline and at least one post-baseline result.
EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not \>=3 on 1 item nor \>=2 on 2 items; abnormal endpoint is defined as a score \>=3 on 1 item or \>=2 on 2 items, or an increase of 3 on Parkinsonism total. 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.
Outcome measures
| Measure |
Olanzapine
n=385 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)
Akathisia (N=378)
|
0.8 percentage of participants
|
—
|
|
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)
Dyskinesia (N=385)
|
0.3 percentage of participants
|
—
|
|
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)
Dystonia (N=385)
|
0.0 percentage of participants
|
—
|
|
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)
Parkinsonism (N=385)
|
1.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=383 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Baseline-Standing Diastolic (N=361)
|
74.98 millimeters of mercury
Standard Deviation 10.77
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Change- Standing Diastolic (N=361)
|
0.15 millimeters of mercury
Standard Deviation 8.28
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Baseline- Sitting Diastolic (N=383)
|
73.32 millimeters of mercury
Standard Deviation 10.73
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Change- Sitting Diastolic (N=383)
|
-0.03 millimeters of mercury
Standard Deviation 8.68
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Baseline- Standing Systolic (N=361)
|
112.06 millimeters of mercury
Standard Deviation 14.58
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Change- Standing Systolic (N=361)
|
0.96 millimeters of mercury
Standard Deviation 10.37
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Baseline- Sitting Systolic (N=383)
|
112.26 millimeters of mercury
Standard Deviation 14.45
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Change- Sitting Systolic (N=383)
|
0.27 millimeters of mercury
Standard Deviation 10.28
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Baseline- Orthostatic Change-Diastolic (N=358)
|
1.75 millimeters of mercury
Standard Deviation 5.25
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Change- Orthostatic Change- Diastolic (N=358)
|
0.16 millimeters of mercury
Standard Deviation 6.56
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Baseline- Orthostatic Change- Systolic (N=358)
|
0.19 millimeters of mercury
Standard Deviation 6.19
|
—
|
|
Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)
Change- Orthostatic Change- Systolic (N=358)
|
0.65 millimeters of mercury
Standard Deviation 7.92
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=384 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Weight (Open-Label Phase)
Baseline
|
68.31 kilograms
Standard Deviation 18.54
|
—
|
|
Change From Baseline to Endpoint in Weight (Open-Label Phase)
Change
|
2.27 kilograms
Standard Deviation 4.00
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=381 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)
Baseline- Albumin
|
42.64 gram/Liter
Standard Deviation 3.58
|
—
|
|
Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)
Change- Albumin
|
0.53 gram/Liter
Standard Deviation 2.86
|
—
|
|
Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)
Baseline- Total Protein
|
73.24 gram/Liter
Standard Deviation 4.39
|
—
|
|
Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)
Change- Total Protein
|
0.56 gram/Liter
Standard Deviation 3.78
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=381 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
Baseline- Alkaline Phosphatase
|
68.58 units/Liter
Standard Deviation 19.33
|
—
|
|
Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
Change- Alkaline Phosphatase
|
2.37 units/Liter
Standard Deviation 12.85
|
—
|
|
Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
Baseline- CPK
|
107.36 units/Liter
Standard Deviation 133.21
|
—
|
|
Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
Change- CPK
|
-1.73 units/Liter
Standard Deviation 124.56
|
—
|
|
Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
Baseline- GGT
|
28.90 units/Liter
Standard Deviation 32.08
|
—
|
|
Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)
Change- GGT
|
0.78 units/Liter
Standard Deviation 25.90
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=381 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Chloride (Open-Label Phase)
Baseline
|
103.62 millimole/Liter
Standard Deviation 2.16
|
—
|
|
Change From Baseline to Endpoint in Chloride (Open-Label Phase)
Change
|
0.33 millimole/Liter
Standard Deviation 2.38
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=381 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Creatinine (Open-Label Phase)
Baseline
|
67.48 micromole/Liter
Standard Deviation 14.98
|
—
|
|
Change From Baseline to Endpoint in Creatinine (Open-Label Phase)
Change
|
2.05 micromole/Liter
Standard Deviation 7.90
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=380 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase)
Baseline
|
4.64 trillion cells per liter (Tril/L)
Standard Deviation 0.53
|
—
|
|
Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase)
Change
|
0.03 trillion cells per liter (Tril/L)
Standard Deviation 0.30
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=380 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase)
Baseline
|
8.61 millimole/Liter of iron (Fe)
Standard Deviation 1.01
|
—
|
|
Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase)
Change
|
0.04 millimole/Liter of iron (Fe)
Standard Deviation 0.51
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=380 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Platelet Count (Open-Label Phase)
Baseline
|
257.96 billion cells per liter (BILL/L)
Standard Deviation 64.25
|
—
|
|
Change From Baseline to Endpoint in Platelet Count (Open-Label Phase)
Change
|
-4.56 billion cells per liter (BILL/L)
Standard Deviation 49.94
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=346 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Prolactin (Open-Label Phase)
Baseline
|
21.64 microgram/Liter
Standard Deviation 18.48
|
—
|
|
Change From Baseline to Endpoint in Prolactin (Open-Label Phase)
Change
|
-3.41 microgram/Liter
Standard Deviation 17.20
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=381 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Uric Acid (Open-Label Phase)
Baseline
|
324.74 micromole/Liter
Standard Deviation 89.39
|
—
|
|
Change From Baseline to Endpoint in Uric Acid (Open-Label Phase)
Change
|
14.73 micromole/Liter
Standard Deviation 56.80
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=380 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Baseline- Fasting Glucose (N=375)
|
5.20 millimole/Liter
Standard Deviation 0.57
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Change- Fasting Glucose (N=375)
|
0.06 millimole/Liter
Standard Deviation 0.63
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Baseline- Cholesterol (N=380)
|
4.96 millimole/Liter
Standard Deviation 1.08
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Change- Cholesterol (N=380)
|
0.05 millimole/Liter
Standard Deviation 0.70
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Baseline- Triglycerides (N=380)
|
1.55 millimole/Liter
Standard Deviation 1.06
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Change- Triglycerides (N=380)
|
0.10 millimole/Liter
Standard Deviation 0.97
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Baseline- LDL Cholesterol (N=378)
|
2.88 millimole/Liter
Standard Deviation 0.91
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Change- LDL Cholesterol (N=378)
|
0.06 millimole/Liter
Standard Deviation 0.63
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Baseline- HDL Cholesterol (N=380)
|
1.39 millimole/Liter
Standard Deviation 0.40
|
—
|
|
Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)
Change- HDL Cholesterol (N=380)
|
-0.05 millimole/Liter
Standard Deviation 0.24
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval).
Outcome measures
| Measure |
Olanzapine
n=366 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in ECG (Open-Label Phase)
Baseline- QTcF
|
410.09 milliseconds
Standard Deviation 19.44
|
—
|
|
Change From Baseline to Endpoint in ECG (Open-Label Phase)
Change- QTcF
|
1.80 milliseconds
Standard Deviation 15.07
|
—
|
|
Change From Baseline to Endpoint in ECG (Open-Label Phase)
Baseline- QTcB
|
421.72 milliseconds
Standard Deviation 19.61
|
—
|
|
Change From Baseline to Endpoint in ECG (Open-Label Phase)
Change- QTcB
|
1.76 milliseconds
Standard Deviation 16.69
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)Population: Participants who entered Open-Label Phase with non-missing baseline (end of Acute Phase) and post-baseline visit, last observation carried forward (LOCF).
Outcome measures
| Measure |
Olanzapine
n=370 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Change From Baseline to Endpoint in Heart Rate (Open-Label Phase)
Baseline
|
71.85 beats per minute
Standard Deviation 11.64
|
—
|
|
Change From Baseline to Endpoint in Heart Rate (Open-Label Phase)
Change
|
0.06 beats per minute
Standard Deviation 10.79
|
—
|
SECONDARY outcome
Timeframe: Endpoint (Week 24)Population: Total participants in the open-label extension phase.
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).
Outcome measures
| Measure |
Olanzapine
n=389 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase)
|
1.3 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)Population: Total participants in the open-label extension phase.
Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events.
Outcome measures
| Measure |
Olanzapine
n=389 Participants
During double-blind treatment, participants receive olanzapine at a dose of 5 mg which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
|
Placebo
Matching placebo administered once daily, by mouth during double-blind treatment.
|
|---|---|---|
|
Number of Participants With Adverse Events (Open-Label Phase)
Serious
|
14 participants
|
—
|
|
Number of Participants With Adverse Events (Open-Label Phase)
Non-Serious
|
209 participants
|
—
|
Adverse Events
Olanzapine
Serious events: 6 serious events
Other events: 238 other events
Deaths: 0 deaths
Placebo
Serious events: 7 serious events
Other events: 88 other events
Deaths: 0 deaths
Olanzapine (Open Label Treatment Period
Serious events: 14 serious events
Other events: 209 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Olanzapine
n=343 participants at risk
During double-blind treatment, participants receive olanzapine at a dose of 5 mg. which is increased to 10 mg. per day no later than 3-7 days after Visit 2. Subsequent dose increases above 10 mg. (up to a maximum of 20 mg per day) are permitted in 5 mg. per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg. requires study discontinuation.
|
Placebo
n=171 participants at risk
Matching placebo administered once daily, by mouth during double-blind treatment.
|
Olanzapine (Open Label Treatment Period
n=389 participants at risk
During open-label treatment, participants randomized to placebo in double-blind period will receive olanzapine 5 mg starting at Visit 9. Participants randomized to olanzapine must be at a 5 mg olanzapine dose at Visit 10. Those on higher doses will be reduced between Visit 9 and 10 (10 mg reduced to 5 mg; 15 mg reduced to 10 mg and then to 5 mg at visit 10; 20 mg reduced to 15 mg and then 10 mg to dosing at 5 mg at visit 10). Dose increases beyond visit 10 are permitted and at the investigator's discretion.
|
|---|---|---|---|
|
Gastrointestinal disorders
Pancreatitis
|
0.29%
1/343 • Number of events 1
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
|
Hepatobiliary disorders
Biliary tract disorder
|
0.00%
0/343
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
0.29%
1/343 • Number of events 1
|
0.00%
0/171
|
0.00%
0/389
|
|
Infections and infestations
Appendicitis
|
0.00%
0/343
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
|
Injury, poisoning and procedural complications
Drug exposure during pregnancy
|
0.00%
0/343
|
0.58%
1/171 • Number of events 1
|
0.00%
0/389
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/343
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
|
Nervous system disorders
Paralysis
|
0.29%
1/343 • Number of events 1
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
|
Psychiatric disorders
Adjustment disorder
|
0.00%
0/343
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/343
|
0.58%
1/171 • Number of events 1
|
0.00%
0/389
|
|
Psychiatric disorders
Bipolar I disorder
|
0.29%
1/343 • Number of events 1
|
1.2%
2/171 • Number of events 2
|
0.26%
1/389 • Number of events 1
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/343
|
0.00%
0/171
|
0.51%
2/389 • Number of events 2
|
|
Psychiatric disorders
Depression
|
0.00%
0/343
|
0.58%
1/171 • Number of events 1
|
0.26%
1/389 • Number of events 1
|
|
Psychiatric disorders
Depressive symptom
|
0.00%
0/343
|
0.58%
1/171 • Number of events 1
|
0.00%
0/389
|
|
Psychiatric disorders
Hallucination, auditory
|
0.00%
0/343
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/343
|
0.58%
1/171 • Number of events 1
|
0.00%
0/389
|
|
Psychiatric disorders
Mania
|
0.00%
0/343
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
|
Psychiatric disorders
Suicidal ideation
|
0.29%
1/343 • Number of events 1
|
1.2%
2/171 • Number of events 2
|
0.26%
1/389 • Number of events 1
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/343
|
0.00%
0/171
|
0.51%
2/389 • Number of events 2
|
|
Vascular disorders
Hypertension
|
0.29%
1/343 • Number of events 1
|
0.00%
0/171
|
0.26%
1/389 • Number of events 1
|
Other adverse events
| Measure |
Olanzapine
n=343 participants at risk
During double-blind treatment, participants receive olanzapine at a dose of 5 mg. which is increased to 10 mg. per day no later than 3-7 days after Visit 2. Subsequent dose increases above 10 mg. (up to a maximum of 20 mg per day) are permitted in 5 mg. per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg. requires study discontinuation.
|
Placebo
n=171 participants at risk
Matching placebo administered once daily, by mouth during double-blind treatment.
|
Olanzapine (Open Label Treatment Period
n=389 participants at risk
During open-label treatment, participants randomized to placebo in double-blind period will receive olanzapine 5 mg starting at Visit 9. Participants randomized to olanzapine must be at a 5 mg olanzapine dose at Visit 10. Those on higher doses will be reduced between Visit 9 and 10 (10 mg reduced to 5 mg; 15 mg reduced to 10 mg and then to 5 mg at visit 10; 20 mg reduced to 15 mg and then 10 mg to dosing at 5 mg at visit 10). Dose increases beyond visit 10 are permitted and at the investigator's discretion.
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
5.5%
19/343 • Number of events 21
|
2.9%
5/171 • Number of events 5
|
1.5%
6/389 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
7/343 • Number of events 8
|
3.5%
6/171 • Number of events 6
|
1.3%
5/389 • Number of events 5
|
|
Gastrointestinal disorders
Dry mouth
|
5.2%
18/343 • Number of events 18
|
3.5%
6/171 • Number of events 6
|
1.0%
4/389 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
2.0%
7/343 • Number of events 7
|
4.7%
8/171 • Number of events 9
|
1.0%
4/389 • Number of events 4
|
|
General disorders
Fatigue
|
2.9%
10/343 • Number of events 10
|
3.5%
6/171 • Number of events 8
|
0.77%
3/389 • Number of events 3
|
|
General disorders
Thirst
|
3.2%
11/343 • Number of events 11
|
0.58%
1/171 • Number of events 1
|
0.26%
1/389 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
3.2%
11/343 • Number of events 11
|
0.58%
1/171 • Number of events 1
|
1.5%
6/389 • Number of events 6
|
|
Infections and infestations
Nasopharyngitis
|
7.0%
24/343 • Number of events 25
|
3.5%
6/171 • Number of events 6
|
5.1%
20/389 • Number of events 25
|
|
Infections and infestations
Upper respiratory tract infection
|
1.7%
6/343 • Number of events 7
|
3.5%
6/171 • Number of events 7
|
0.77%
3/389 • Number of events 3
|
|
Investigations
Alanine aminotransferase increased
|
3.2%
11/343 • Number of events 11
|
0.00%
0/171
|
3.1%
12/389 • Number of events 13
|
|
Investigations
Weight increased
|
17.2%
59/343 • Number of events 59
|
3.5%
6/171 • Number of events 6
|
17.2%
67/389 • Number of events 67
|
|
Metabolism and nutrition disorders
Increased appetite
|
13.4%
46/343 • Number of events 46
|
2.3%
4/171 • Number of events 5
|
3.9%
15/389 • Number of events 15
|
|
Nervous system disorders
Akathisia
|
4.1%
14/343 • Number of events 14
|
1.2%
2/171 • Number of events 2
|
2.3%
9/389 • Number of events 9
|
|
Nervous system disorders
Dizziness
|
3.8%
13/343 • Number of events 13
|
3.5%
6/171 • Number of events 6
|
1.5%
6/389 • Number of events 6
|
|
Nervous system disorders
Headache
|
4.4%
15/343 • Number of events 17
|
4.7%
8/171 • Number of events 9
|
2.6%
10/389 • Number of events 12
|
|
Nervous system disorders
Hypersomnia
|
4.4%
15/343 • Number of events 15
|
1.2%
2/171 • Number of events 2
|
3.6%
14/389 • Number of events 14
|
|
Nervous system disorders
Sedation
|
8.5%
29/343 • Number of events 33
|
2.3%
4/171 • Number of events 4
|
0.77%
3/389 • Number of events 3
|
|
Nervous system disorders
Somnolence
|
17.2%
59/343 • Number of events 60
|
6.4%
11/171 • Number of events 11
|
4.4%
17/389 • Number of events 20
|
|
Nervous system disorders
Tremor
|
4.1%
14/343 • Number of events 15
|
2.9%
5/171 • Number of events 5
|
1.8%
7/389 • Number of events 7
|
|
Psychiatric disorders
Anxiety
|
3.2%
11/343 • Number of events 13
|
2.9%
5/171 • Number of events 5
|
2.6%
10/389 • Number of events 10
|
|
Psychiatric disorders
Insomnia
|
3.2%
11/343 • Number of events 11
|
4.7%
8/171 • Number of events 8
|
2.1%
8/389 • Number of events 9
|
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