Recruitment Details

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

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

Reporting Groups

	Description
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.

Participant Flow for 2 periods

Period 1:   Double-Blind Treatment

	Olanzapine	Placebo
STARTED	343	171
COMPLETED	267	122
NOT COMPLETED	76	49
Adverse Event	30	13
Lack of Efficacy	6	13
Lost to Follow-up	3	7
Physician Decision	6	0
Protocol Violation	1	2
Withdrawal by Subject	27	13
Clinical Relapse	0	1
Entry Criteria Not Met	3	0

Period 2:   Open-Label Treatment

	Olanzapine	Placebo
STARTED	267	122
COMPLETED	196	96
NOT COMPLETED	71	26
Adverse Event	22	8
Death	1	1
Lack of Efficacy	4	0
Lost to Follow-up	10	1
Physician Decision	3	1
Protocol Violation	4	2
Withdrawal by Subject	24	12
Clinical Relapse	1	1
Sponsor Decision	2	0

Reporting Groups

	Description
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.

Baseline Measures

	Olanzapine	Placebo	Total
Number of Participants   [units: participants]	343	171	514
Age   [units: years] Mean ± Standard Deviation	35.93  ± 11.13	34.96  ± 11.02	35.61  ± 11.09
Gender   [units: participants]
Female	205	95	300
Male	138	76	214
Race/Ethnicity, Customized   [units: participants]
Caucasian	36	22	58
African	18	4	22
Hispanic	6	3	9
East Asian	282	141	423
Native American	1	1	2
Region of Enrollment   [units: participants]
China	140	70	210
Japan	104	52	156
Korea, Republic of	20	10	30
Taiwan	19	9	28
United States	60	30	90
Age at onset, Bipolar I Disorder   [units: years] Mean ± Standard Deviation	27.57  ± 10.98	26.12  ± 9.90	27.09  ± 10.64

1.  Primary:

Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

2.  Secondary:

Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase)   [ Time Frame: Endpoint (Week 6) ]

3.  Secondary:

Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase)   [ Time Frame: Baseline through Endpoint (Week 6) ]

4.  Secondary:

Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

5.  Secondary:

Percentage of Participants With Recovery (Acute Phase)   [ Time Frame: Baseline through Endpoint (Week 6 ) ]

6.  Secondary:

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

7.  Secondary:

Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

8.  Secondary:

Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase)   [ Time Frame: Endpoint (Week 6) ]

9.  Secondary:

Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase)   [ Time Frame: Endpoint (Week 6) ]

10.  Secondary:

Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase)   [ Time Frame: Endpoint (Week 6) ]

11.  Secondary:

Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)   [ Time Frame: Endpoint (Week 6) ]

12.  Secondary:

Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase)   [ Time Frame: Endpoint (Week 6) ]

13.  Secondary:

Percentage of Participants With Emergence of Mania During the Study (Acute Phase)   [ Time Frame: Baseline through Endpoint (Week 6) ]

14.  Secondary:

Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)   [ Time Frame: Endpoint (Week 6) ]

15.  Secondary:

Change From Baseline to Endpoint in Blood Pressure (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

16.  Secondary:

Change From Baseline to Endpoint in Weight (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

17.  Secondary:

Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)   [ Time Frame: Baseline, Endpoint (Week 6) ]

18.  Secondary:

Change From Baseline to Endpoint in Albumin (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

19.  Secondary:

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)   [ Time Frame: Baseline, Endpoint (Week 6) ]

20.  Secondary:

Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

21.  Secondary:

Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

22.  Secondary:

Change From Baseline to Endpoint in Hematocrit (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

23.  Secondary:

Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

24.  Secondary:

Change From Baseline to Endpoint in Hemoglobin (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

25.  Secondary:

Change From Baseline to Endpoint in Prolactin (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

26.  Secondary:

Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

27.  Secondary:

Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

28.  Secondary:

Change From Baseline to Endpoint in Heart Rate (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

29.  Secondary:

Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)   [ Time Frame: Baseline, Endpoint (Week 6) ]

30.  Secondary:

Number of Participants With Adverse Events (Acute Phase)   [ Time Frame: Baseline through Week 6 (Acute Phase) ]

31.  Secondary:

Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) ]

32.  Secondary:

Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) ]

33.  Secondary:

Percentage of Participants With Recovery (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) ]

34.  Secondary:

Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

35.  Secondary:

Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) ]

36.  Secondary:

Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)   [ Time Frame: Endpoint (Week 24) ]

37.  Secondary:

Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

38.  Secondary:

Change From Baseline to Endpoint in Weight (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24) ]

39.  Secondary:

Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

40.  Secondary:

Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

41.  Secondary:

Change From Baseline to Endpoint in Chloride (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

42.  Secondary:

Change From Baseline to Endpoint in Creatinine (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

43.  Secondary:

Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

44.  Secondary:

Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

45.  Secondary:

Change From Baseline to Endpoint in Platelet Count (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

46.  Secondary:

Change From Baseline to Endpoint in Prolactin (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

47.  Secondary:

Change From Baseline to Endpoint in Uric Acid (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

48.  Secondary:

Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

49.  Secondary:

Change From Baseline to Endpoint in ECG (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

50.  Secondary:

Change From Baseline to Endpoint in Heart Rate (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24) ]

51.  Secondary:

Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase)   [ Time Frame: Endpoint (Week 24) ]

52.  Secondary:

Number of Participants With Adverse Events (Open-Label Phase)   [ Time Frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24) ]