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A Study in Relapse Prevention of Treatment-Resistant Depression

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ClinicalTrials.gov Identifier: NCT00958568
Recruitment Status : Completed
First Posted : August 13, 2009
Results First Posted : April 1, 2014
Last Update Posted : April 1, 2014
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Treatment Resistant Depression
Interventions Drug: Olanzapine and Fluoxetine combination (OFC)
Drug: Fluoxetine
Enrollment 892
Recruitment Details  
Pre-assignment Details The study consisted of 4 treatment phases: a screening phase (Study Period I [SPI]) of 3 to 14 days; a 6- to 8-week (wk) acute open-label treatment phase (SPII); a 12-week open-label stabilization treatment phase (SPIII); and a 27-week double-blind (DB) randomized relapse prevention treatment phase (SPIV).
Arm/Group Title OFC (SPII ) OFC (SPIII) OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description Olanzapine and Fluoxetine Combination (OFC): 3 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (3/25), 6/25, 12/25, 6/50, 12/50 or 18/50, oral, daily, for 6-8 weeks during open-label acute treatment phase (SPII). Flexible dosing with initial forced titration. 6 mg Olanzapine and 25 mg Fluoxetine Combination (OFC): 6 mg Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50 oral, daily, for 12 weeks during open-label stabilization treatment phase (SPIII). Flexible dosing. Olanzapine and Fluoxetine Combination (OFC): 6 mg Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV). Fixed dosing. Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Period Title: SPII (Wk 0-8, Acute Open-label)
Started 892 0 0 0
Completed 655 0 0 0
Not Completed 237 0 0 0
Reason Not Completed
Response Criteria Not Met             80             0             0             0
Adverse Event             44             0             0             0
Entry Criteria Not Met             34             0             0             0
Withdrawal by Subject             39             0             0             0
Lost to Follow-up             14             0             0             0
Protocol Violation             13             0             0             0
Physician Decision             4             0             0             0
Sponsor Decision             8             0             0             0
Unknown, Not Otherwise Specified             1             0             0             0
Period Title: SPIII (Wk 9-20,Open-label Stabilization)
Started 0 655 0 0
Completed 0 444 0 0
Not Completed 0 211 0 0
Reason Not Completed
Stabilization Criteria Not Met             0             62             0             0
Blinded Randomization Criteria Not Met             0             30             0             0
Adverse Event             0             28             0             0
Withdrawal by Subject             0             41             0             0
Protocol Violation             0             24             0             0
Lost to Follow-up             0             9             0             0
Entry Criteria Not Met             0             6             0             0
Sponsor Decision             0             5             0             0
Physician Decision             0             4             0             0
Relapse Criteria Met             0             1             0             0
Unknown, Not Otherwise Specified             0             1             0             0
Period Title: SPIV (Wk 21-47, DB Relapse Prevention)
Started 0 0 221 223
Completed 0 0 139 117
Not Completed 0 0 82 106
Reason Not Completed
Relapse Criteria Met             0             0             24             63
Adverse Event             0             0             19             10
Withdrawal by Subject             0             0             16             15
Protocol Violation             0             0             11             5
Lost to Follow-up             0             0             3             8
Sponsor Decision             0             0             5             4
Entry Criteria Not Met             0             0             2             1
Death             0             0             1             0
Physician Decision             0             0             1             0
Arm/Group Title OFC (SPII-Wk 0-8, Acute Open-label)
Hide Arm/Group Description Olanzapine and Fluoxetine Combination (OFC): 3 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (3/25), 6/25, 12/25, 6/50, 12/50 or 18/50, oral, daily, for 6-8 weeks during open-label acute treatment phase (SPII). Flexible dosing with initial forced titration.
Overall Number of Baseline Participants 892
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 892 participants
44.38  (11.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 892 participants
Female
591
  66.3%
Male
301
  33.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 892 participants
Hispanic or Latino
167
  18.7%
Not Hispanic or Latino
725
  81.3%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 892 participants
American Indian or Alaska Native
27
   3.0%
Asian
115
  12.9%
Native Hawaiian or Other Pacific Islander
1
   0.1%
Black or African American
101
  11.3%
White
634
  71.1%
More than one race
11
   1.2%
Unknown or Not Reported
3
   0.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 892 participants
United States 533
Mexico 44
Puerto Rico 20
Argentina 53
Turkey 28
Russian Federation 66
South Africa 40
India 108
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms/square meter (kg/m²)
Number Analyzed 892 participants
29.12  (7.36)
[1]
Measure Description: N=892, data was not reported for 1 participant
1.Primary Outcome
Title Time to Relapse by Any Criteria
Hide Description Relapse defined as meeting any of these criteria: 50% increase in Montgomery-Asberg Depression Rating Scale (MADRS) score from randomization with a Clinical Global Impressions-Severity (CGI-S) of Depression score increase to a score of 4 or more; Hospitalized for depression or suicidality; Discontinued due to lack of efficacy/worsening of depression/suicidality. MADRS is a 10-item rating scale for depressive mood symptoms severity, items rated on 0-6 scale, with total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). CGI-S measures severity of illness at time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (the most extremely ill). Lack of Efficacy/Worsening of depression was at discretion of investigator based on clinical observation. Suicidality is thoughts or actions of self-harm as determined by the investigator. Those who did not relapse were "censored" at their last observation.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants are included in the time to event analyses. The numbers of participants censored are 186 and 152 for OFC and Flu groups, respectively.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Median (Full Range)
Unit of Measure: days
NA [1] 
(6.0 to NA)
NA [1] 
(7.0 to NA)
[1]
Not calculable due to few participants reaching the time-to-event endpoint of relapse at study completion.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments Power estimate assumes approximately 1230 participants enter SPII. With a 60% drop-out/disqualification rate in SPII, then 492 participants enter SPIII. If 26% of participants drop out during SPIII, then 364 participants enter SPIV. Assuming 20% drop-out rate, 25% relapse rate on OFC and 40% relapse rate for fluoxetine (hazard ratio = 0.56), the log-rank test is 80% powered to detect a difference at a 2-sided 0.05 level. A total of 95 relapse events during SPIV should satisfy these assumptions.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Relapse by Any Criteria
Hide Description Relapse is defined as meeting any of the following criteria: 50% increase in Montgomery-Asberg Depression Rating Scale (MADRS) score from randomization with concomitant Clinical Global Impressions-Severity (CGI-S) of Depression score increase to a score of 4 or more; Hospitalization for depression or suicidality; Discontinuation due to lack of efficacy/worsening of depression/suicidality. MADRS is a rating scale for severity of depressive mood symptoms with 10 items 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). CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (the most extremely ill). Lack of Efficacy/Worsening of depression was at the discretion of the investigator and based on clinical observation. Suicidality is thoughts or actions of self-harm as determined by the investigator.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Unit of Measure: percentage of participants
15.8 31.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments Relapse rates were analyzed using the Cochran-Mantel-Haenszel test adjusting for country.
3.Secondary Outcome
Title Percentage of Participants Who Relapse Based on Montgomery-Åsberg Depression Rating Scale (MADRS) Score With Concomitant Clinical Global Impressions-Severity (CGI-S) of Depression Score
Hide Description Relapse is defined as a 50% increase in the Montgomery-Asberg Depression Rating Scale (MADRS) score from randomization with concomitant Clinical Global Impressions-Severity (CGI-S) of Depression score increase to a score of 4 or more. The MADRS has a 10-item checklist with items 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). CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (the most extremely ill).
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Unit of Measure: percentage of participants
14.0 28.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments Relapse rates were analyzed using the Cochran-Mantel-Haenszel test adjusting for country.
4.Secondary Outcome
Title Percentage of Participants Who Relapse as Measured by Hospitalization for Depression or Suicidality
Hide Description [Not Specified]
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Unit of Measure: percentage of participants
1.8 1.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.713
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments Relapse rates were analyzed using the Cochran-Mantel-Haenszel test adjusting for country.
5.Secondary Outcome
Title Percentage of Participants Who Relapse as Measured by Discontinuation Due to Lack of Efficacy/Worsening of Depression/Suicidality
Hide Description Lack of Efficacy/Worsening of depression was at the discretion of the investigator and was based on clinical observation. Suicidality is thoughts or actions of self-harm as determined by the investigator.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Unit of Measure: percentage of participants
10.9 28.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments Relapse rates were analyzed using the Cochran-Mantel-Haenszel test adjusting for country.
6.Secondary Outcome
Title Time to Relapse Based on the Montgomery-Åsberg Depression Rating Scale (MADRS) Score With Concomitant Clinical Global Impressions-Severity (CGI-S) of Depression Score
Hide Description Relapse is defined as a 50% increase in the Montgomery-Asberg Depression Rating Scale (MADRS) score from randomization with concomitant Clinical Global Impressions-Severity (CGI-S) of Depression score increase to a score of 4 or more. The MADRS has a 10-item checklist with items 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). CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (the most extremely ill). Those who did not relapse were "censored" at their last observation.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants are included in the time to event analyses. The numbers of participants censored are 190 and 160 for OFC and Flu groups, respectively.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Median (Full Range)
Unit of Measure: days
NA [1] 
(6 to NA)
NA [1] 
(7 to NA)
[1]
Not calculable due to few participants reaching the time-to-event endpoint of relapse at study completion.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Log Rank
Comments [Not Specified]
7.Secondary Outcome
Title Time to Relapse as Measured by Hospitalization for Depression or Suicidality
Hide Description Those who did not relapse were "censored" at their last observation.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants are included in the time to event analyses. The numbers of participants censored are 217 and 220 for OFC and Flu groups, respectively.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Median (Full Range)
Unit of Measure: days
NA [1] 
(6 to NA)
NA [1] 
(7 to NA)
[1]
Not calculable due to few participants reaching the time-to-event endpoint of relapse at study completion.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.831
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Log Rank
Comments [Not Specified]
8.Secondary Outcome
Title Time to Relapse as Measured by Discontinuation Due to Lack of Efficacy/Worsening of Depression/Suicidality
Hide Description Lack of Efficacy/Worsening of depression was at the discretion of the investigator and was based on clinical observation. Suicidality is thoughts or actions of self-harm as determined by the investigator. Those who did not relapse were "censored" at their last observation.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants are included in the time to event analyses. The numbers of participants censored are 197 and 160 for OFC and Flu groups, respectively.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Median (Full Range)
Unit of Measure: days
NA [1] 
(6 to NA)
NA [1] 
(7 to NA)
[1]
Not calculable due to few participants reaching the time-to-event endpoint of relapse at study completion.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Log Rank
Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants Responding to Treatment During Open-Label Acute Treatment Phase
Hide Description A 50% or greater improvement from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) and a Clinical Global Impressions-Severity (CGI-S) of Depression score ≤3 will be considered as response criteria met. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist with items 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). CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time Frame Week 0 to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who entered open-label acute treatment phase (SPII).
Arm/Group Title OFC (SPII-Wk 0-8, Acute Open-label)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 3 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (3/25), 6/25, 12/25, 6/50, 12/50 or 18/50, oral, daily, for 6-8 weeks during open-label acute treatment phase (SPII). Flexible dosing with initial forced titration.
Overall Number of Participants Analyzed 892
Measure Type: Number
Unit of Measure: percentage of participants
78.0
10.Secondary Outcome
Title Percentage of Participants Maintaining Response at Any Point During Stabilization Treatment Phase
Hide Description A 50% or greater improvement from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) and a Clinical Global Impressions-Severity (CGI-S) of Depression score ≤3 will be considered as response criteria met. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist with items 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). CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time Frame Week 8 to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who entered open-label stabilization treatment phase (SPIII).
Arm/Group Title OFC (SPIII)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 mg Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50 oral, daily, for 12 weeks during open-label stabilization treatment phase (SPIII). Flexible dosing.
Overall Number of Participants Analyzed 655
Measure Type: Number
Unit of Measure: percentage of participants
68.2
11.Secondary Outcome
Title Percentage of Participants Achieving Remission at Any Point During Stabilization Treatment Phase
Hide Description Remission is defined as the Montgomery-Asberg Depression Rating Scale (MADRS) score ≤8. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time Frame Week 8 to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who entered open-label stabilization treatment phase (SPIII).
Arm/Group Title OFC (SPIII)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 mg Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50 oral, daily, for 12 weeks during open-label stabilization treatment phase (SPIII). Flexible dosing.
Overall Number of Participants Analyzed 655
Measure Type: Number
Unit of Measure: percentage of participants
77.9
12.Secondary Outcome
Title Percentage of Participants Maintaining Remission
Hide Description Remission is defined as the Montgomery-Asberg Depression Rating Scale (MADRS) score ≤8. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist with items rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Unit of Measure: percentage of participants
86.4 78.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Cochran-Mantel-Haenszel
Comments Remission rates were analyzed using the Cochran-Mantel-Haenszel test adjusting for country.
13.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Montgomery-Asberg Depression Rating Scale (MADRS) Using Mixed-Effects Model Repeated Measures (MMRM) Analysis
Hide Description The MADRS has a 10-item checklist with items 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). Least Squares (LS) Mean values were controlled for baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) MADRS measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 220 221
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.06  (0.56) 4.97  (0.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.91
Confidence Interval (2-Sided) 95%
-4.46 to -1.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.78
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Montgomery-Asberg Depression Rating Scale (MADRS) Using Last Observation Carried Forward (LOCF) Analysis
Hide Description The MADRS has a 10-item checklist with items 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). Least Squares (LS) Mean values were controlled for baseline (Week 20), treatment and country.
Time Frame Randomization (Week 20), up to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) MADRS measurements. LOCF principle was used.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 220 221
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.03  (0.71) 6.84  (0.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment and country.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.82
Confidence Interval (2-Sided) 95%
-5.39 to -2.24
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Clinical Global Impressions - Severity (CGI-S) of Depression Using Mixed-Effects Model Repeated Measures (MMRM) Analysis
Hide Description CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) Mean values were controlled for baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) CGI-S measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 220 221
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.20  (0.08) 0.54  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.55 to -0.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Resource Utilization - Average Number of Hours Worked for Pay Per Week at Week 47
Hide Description [Not Specified]
Time Frame Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who worked for pay at Week 47.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 70 63
Mean (Standard Deviation)
Unit of Measure: hours
37.49  (16.95) 37.76  (14.58)
17.Secondary Outcome
Title Resource Utilization (Number of Psychiatric Visits, Number of Emergency Room or Equivalent Facility Visits for Psychiatric Illness)
Hide Description Resource utilization is defined as the average number of psychiatric visits and number of emergency room or equivalent facility visits for psychiatric illness.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who provided information of psychiatric visits and emergency room or equivalent facility visits for psychiatric illness from Week 21 to Week 47.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 138 115
Mean (Standard Deviation)
Unit of Measure: visits per participant
Psychiatric visits (n=136, 113) 0.65  (1.43) 0.81  (1.52)
Emergency room or equivalent facility visits 0.00  (0.00) 0.00  (0.00)
18.Secondary Outcome
Title Change From Week 20 to Week 47 Endpoint in the Sheehan Disability Scale (SDS)
Hide Description The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work or school (Item 1), social (Item 2), and family life and home responsibilities (Item 3). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Total scores is the sum of the 3 items and range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Least Squares (LS) Mean values were controlled for baseline (Week 20), treatment and country.
Time Frame Randomization (Week 20), up to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) SDS score measurements. Last observation carried forward (LOCF) principle was used.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 154 167
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.30  (0.72) 3.24  (0.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment and country.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.94
Confidence Interval (2-Sided) 95%
-3.36 to -0.53
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.72
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Percent of Participants With Treatment-Emergent Akathisia
Hide Description Barnes Akathisia Scale (BAS) rates observable, restless movements of drug-induced akathisia as well as the subjective awareness of restlessness and any distress associated with the akathisia. It consists of 4 items. 3 items (objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness) rated on a 4-point scale, with 0 being no akathisia and 3 being severe akathisia. Item 4 (global clinical assessment of Akathisia) is derived from the responses on Items 1-3 rated on a 6-point scale, with 0 being absence and 5 being extreme Akathisia. Treatment emergent akathisia is defined as a global clinical assessment score on BAS <2 at baseline (Week 20) and a global clinical assessment score on BAS ≥2 post-baseline (Weeks 21-47).
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) BAS measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 217 213
Measure Type: Number
Unit of Measure: percentage of participants
0.9 0.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
20.Secondary Outcome
Title Percent of Participants With Treatment-Emergent Parkinsonism
Hide Description Simpson-Angus Scale is used to measure Parkinsonian-type symptoms in participants exposed to neuroleptics. The scale consists of 10 items, each rated on a 5-point scale, with 0 meaning complete absence of the condition and 4 meaning the presence of the condition in extreme form. The total score is obtained by adding the items and ranges from 0-40 with higher scores indicating worse conditions. Treatment emergent parkinsonism is defined as total score ≤3 of items 1 through 10 of the Simpson-Angus scale at baseline (Week 20) and a total score >3 of items 1 through 10 post-baseline (Weeks 21-47).
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) Simpson-Angus Scale measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 214 208
Measure Type: Number
Unit of Measure: percentage of participants
1.4 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.248
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
21.Secondary Outcome
Title Percent of Participants With Treatment-Emergent Dyskinesia
Hide Description Abnormal Involuntary Movement Scale (AIMS) is a 12-item scale designed to record the occurrence of dyskinetic movements. Items 1 through 10 are rated on a 5-point scale, with 0 being no dyskinetic movements and 4 being severe dyskinetic movements. Items 11 and 12 are yes/no questions regarding the dental condition of the participants. Treatment emergent dyskinesia is defined as a score ≥3 on any one of the AIMS items 1-7 post-baseline (Weeks 21-47) or scores ≥2 on any two of the AIMS items 1-7 post-baseline (Weeks 21-47) among participants without either criteria at baseline (Week 20).
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) AIMS measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 212 208
Measure Type: Number
Unit of Measure: percentage of participants
0.5 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
22.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Fasting Total Cholesterol
Hide Description Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and standard error (SE). LS Mean values were controlled for baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) cholesterol measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 212 209
Least Squares Mean (Standard Error)
Unit of Measure: milligrams/deciliter (mg/dL)
-2.65  (3.24) -1.74  (3.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.839
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.91
Confidence Interval (2-Sided) 95%
-9.71 to 7.89
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.47
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Percent of Participants With Treatment-Emergent High Fasting Total Cholesterol
Hide Description Borderline to High fasting total cholesterol: ≥200 milligrams/deciliter (mg/dL) and <240 mg/dL at baseline and ≥240 mg/dL any time post baseline; Normal to Borderline fasting total cholesterol: <200 mg/dL at baseline, ≥200 mg/dL and <240 mg/dL any time post baseline; Normal to High fasting total cholesterol: <200 mg/dL at baseline and ≥240 mg/dL any time post baseline.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had borderline or normal cholesterol level at baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) cholesterol measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 75 83
Measure Type: Number
Unit of Measure: percentage of participants
Borderline to High (n= 75, 83) 28.0 20.5
Normal to Borderline (n=47, 59) 17.0 16.9
Normal to High (n=47, 59) 2.1 3.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.352
Comments P-value is for Borderline to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments P-value is for Normal to Borderline. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments P-value is for Normal to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
24.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Fasting Low-Density Lipoprotein (LDL) Cholesterol
Hide Description Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and standard error (SE). LS Mean values were controlled for baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) LDL cholesterol measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 200 203
Least Squares Mean (Standard Error)
Unit of Measure: milligrams/deciliter (mg/dL)
-0.72  (2.96) 0.85  (3.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.703
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.57
Confidence Interval (2-Sided) 95%
-9.69 to 6.54
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.12
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Percent of Participants With Treatment-Emergent High Fasting Low-Density Lipoprotein (LDL) Cholesterol
Hide Description Borderline to High fasting LDL cholesterol: ≥100 milligrams/deciliter (mg/dL) and <160 mg/dL at baseline and ≥160 mg/dL any time post baseline; Normal to Borderline fasting LDL cholesterol: <100 mg/dL at baseline, ≥100 mg/dL and <160 mg/dL any time post baseline; Normal to High fasting LDL cholesterol: <100 mg/dL at baseline and ≥160 mg/dL any time post baseline.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had borderline or normal LDL cholesterol value at baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) LDL cholesterol measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 115 134
Measure Type: Number
Unit of Measure: percent of participants
Borderline to High (n= 115, 134) 17.4 10.4
Normal to Borderline (n=22, 26) 22.7 30.8
Normal to High (n=22, 26) 4.5 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments P-value is for Borderline to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.746
Comments P-value is for Normal to Borderline. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.458
Comments P-value is for Normal to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
26.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Fasting High-Density Lipoprotein (HDL) Cholesterol
Hide Description Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and standard error (SE). LS Mean values were controlled for baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) HDL cholesterol measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 211 207
Least Squares Mean (Standard Error)
Unit of Measure: milligrams/deciliter (mg/dL)
-1.71  (0.84) 2.02  (0.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.73
Confidence Interval (2-Sided) 95%
-5.99 to -1.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.15
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Percent of Participants With Treatment-Emergent Low Fasting High-Density Lipoprotein (HDL) Cholesterol
Hide Description Normal to Low fasting HDL cholesterol is ≥40 milligrams/deciliter (mg/dL) at baseline and <40 mg/dL anytime post baseline.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had normal HDL cholesterol value at baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) HDL cholesterol measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 199 208
Measure Type: Number
Unit of Measure: percentage of participants
39.2 25.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
28.Secondary Outcome
Title Percent of Participants With Treatment-Emergent Hepatic Events
Hide Description Participants with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3 times the upper limit of normal (ULN) at baseline, with ALT or AST >=3 times the ULN post-baseline and total bilirubin >=2 times ULN at the same time are considered having treatment-emergent hepatic events.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and post-baseline (Weeks 21-47) hepatic function measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 209 208
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
29.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Fasting Triglycerides
Hide Description Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and standard error (SE). LS Mean values were controlled for baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) triglycerides measurement.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 211 209
Least Squares Mean (Standard Error)
Unit of Measure: milligrams/deciliter (mg/dL)
-8.24  (5.70) -21.51  (6.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.083
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 13.27
Confidence Interval (2-Sided) 95%
-1.72 to 28.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 7.62
Estimation Comments [Not Specified]
30.Secondary Outcome
Title Percent of Participants With Treatment-Emergent High Fasting Triglycerides
Hide Description Borderline to High fasting triglycerides: ≥150 milligrams/deciliter (mg/dL) and <200 mg/dL at baseline and ≥200 mg/dL any time post baseline; Normal to Borderline fasting triglycerides: <150 mg/dL at baseline, ≥150 mg/dL and <200 mg/dL any time post baseline; Normal to High fasting triglycerides: <150 mg/dL at baseline and ≥200 mg/dL any time post baseline.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had borderline or normal triglycerides value at baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) triglyceride measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 68 74
Measure Type: Number
Unit of Measure: percentage of participants
Borderline to High (n=47, 41) 51.1 26.8
Normal to Borderline (n= 68, 74) 22.1 6.8
Normal to High (n=68, 74) 16.2 5.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments P-value is for Borderline to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments P-value is for Normal to Borderline. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.054
Comments P-value is for Normal to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
31.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Fasting Glucose
Hide Description Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and standard error (SE). LS Mean values were controlled for baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) glucose measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 200 198
Least Squares Mean (Standard Error)
Unit of Measure: milligrams/deciliter (mg/dL)
3.67  (1.36) -2.22  (1.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 5.89
Confidence Interval (2-Sided) 95%
2.22 to 9.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.87
Estimation Comments [Not Specified]
32.Secondary Outcome
Title Percent of Participants With Treatment-Emergent High Fasting Glucose
Hide Description Impaired to High fasting glucose: ≥100 milligrams/deciliter (mg/dL) and <126 mg/dL at baseline and ≥126 mg/dL any time post baseline; Normal to High glucose: <100 mg/dL at baseline and ≥126 mg/dL any time post baseline; Normal to Impaired fasting glucose is <100 mg/dL at baseline, ≥100 mg/dL and <126 mg/dL any time post baseline; Normal/Impaired to High fasting glucose: <126 mg/dL at baseline and ≥126 mg/dL any time post baseline.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had impaired or normal glucose value at baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) glucose measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 188 193
Measure Type: Number
Unit of Measure: percentage of participants
Impaired to High (n=98, 97) 18.4 7.2
Normal to High (n=90, 96) 4.4 5.2
Normal to Impaired (n=90, 96) 35.6 28.1
Normal/Impaired to High (n= 188, 193) 11.7 6.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments P-value is for Impaired to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments P-value is for Normal to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.344
Comments P-value is for Normal to Impaired. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments P-value is for Normal/Impaired to High. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
33.Secondary Outcome
Title Mean Change From Week 20 to Week 47 in Weight
Hide Description Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and standard error (SE). LS Mean values were controlled for baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) weight measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 220 222
Least Squares Mean (Standard Error)
Unit of Measure: kilograms (kg)
1.14  (0.33) -2.78  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.92
Confidence Interval (2-Sided) 95%
2.96 to 4.88
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.49
Estimation Comments [Not Specified]
34.Secondary Outcome
Title Percent of Participants With Week 20-to-Week 47 Endpoint Increase in Weight of at Least 7%
Hide Description [Not Specified]
Time Frame Week 20 to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had Week 20 and at least 1 post-baseline (Weeks 21-47) weight measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 220 222
Measure Type: Number
Unit of Measure: percentage of participants
11.8 2.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The threshold for statistical significance was 0.05.
Method Fisher Exact
Comments [Not Specified]
35.Secondary Outcome
Title Percent of Participants With Suicide-Related Thoughts and Behaviors
Hide Description Columbia Suicide Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) C-SSRS measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 220 221
Measure Type: Number
Unit of Measure: percentage of participants
Suicidal Ideation 4.1 6.3
Suicidal Behavior 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.392
Comments P-value is for suicidal ideation. The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
36.Secondary Outcome
Title Mean Change in Corrected (for Rate) Cardiac QT Interval Using Fridericia’s Formula (QTcF) on Electrocardiogram
Hide Description Least Squares (LS) Mean values were obtained from a mixed model repeated measures (MMRM) analysis. Model includes baseline (Week 20), treatment, country, visit, and treatment by visit interaction.
Time Frame Randomization (Week 20), Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) electrocardiogram (ECG) measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 201 194
Least Squares Mean (Standard Error)
Unit of Measure: milliseconds (msec)
-3.12  (1.48) -1.55  (1.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OFC (SPIV), Flu (SPIV)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.421
Comments The test was run using an a priori 2-sided threshold for statistical significance of 0.05. No adjustments were made for multiple comparisons.
Method t-test, 2 sided
Comments The model adjusted for baseline (Week 20), treatment, country, visit, and treatment-by-visit interaction.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.57
Confidence Interval (2-Sided) 95%
-5.42 to 2.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.95
Estimation Comments [Not Specified]
37.Secondary Outcome
Title Percent of Participants With Treatment-Emergent Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) on Electrocardiogram ≥500 Milliseconds (Msec)
Hide Description Data presented are the percent of participants whose baseline corrected (for rate) cardiac QT interval <500 msec with post-baseline corrected (for rate) cardiac QT interval ≥500 msec.
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had <500 msec QTc interval at baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) electrocardiogram (ECG) measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 214 214
Measure Type: Number
Unit of Measure: percentage of participants
0 0
38.Secondary Outcome
Title Percent of Participants With a 60 Milliseconds (Msec) Increase in Fridericia-Corrected (for Rate) Cardiac QT Interval (QTcF) on Electrocardiogram
Hide Description [Not Specified]
Time Frame Randomization (Week 20) to Week 47
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had baseline (Week 20) and at least 1 post-baseline (Weeks 21-47) electrocardiogram (ECG) measurements.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 214 214
Measure Type: Number
Unit of Measure: percentage of participants
0 0
39.Other Pre-specified Outcome
Title Kaplan-Meier Estimate of Percentage of Subjects Not Relapsing at Week 27 (Day 189)
Hide Description Relapse is defined as meeting any of the following criteria (Relapse-any reason): 50% increase in MADRS score from randomization with concomitant CGI-S of Depression score increase to a score of 4 or more (MADRS score/CGI-S Depression Score); Hospitalization for depression or suicidality; Discontinuation due to lack of efficacy/worsening of depression/suicidality. MADRS is a rating scale for severity of depressive mood symptoms with 10 items 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). CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (the most extremely ill). Lack of Efficacy/Worsening of depression was at the discretion of the investigator and based on clinical observation. Suicidality is thoughts or actions of self-harm as determined by the investigator.
Time Frame Randomization (Week 20) to Week 27
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description:
Olanzapine and Fluoxetine Combination (OFC): 6 mg Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV). Fixed dosing.
Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Relapse-any criteria
83.6
(77.6 to 88.1)
66.5
(59.6 to 72.5)
Relapse-MADRS score/CGI-S Depression Score
85.3
(79.3 to 89.6)
69.6
(62.7 to 75.5)
Relapse-Hospitalization for depression/suicidality
97.7
(94.0 to 99.1)
98.6
(95.6 to 99.5)
Relapse-Discontinued for lack efficacy/worsening
87.4
(81.7 to 91.4)
69.8
(63.0 to 75.6)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OFC (SPII) OFC (SPIII) OFC (SPIV) Flu (SPIV)
Hide Arm/Group Description Olanzapine and Fluoxetine Combination (OFC): 3 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (3/25), 6/25, 12/25, 6/50, 12/50 or 18/50, oral, daily, for 6-8 weeks during open-label acute treatment phase (SPII). Flexible dosing with initial forced titration. Olanzapine and Fluoxetine Combination (OFC): 6 mg Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50 oral, daily, for 12 weeks during open-label stabilization treatment phase (SPIII). Flexible dosing. Olanzapine and Fluoxetine Combination (OFC): 6 mg Olanzapine and 25 mg Fluoxetine Combination (6/25), 12/25, 6/50, 12/50 or 18/50, oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV). Fixed dosing. Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).
All-Cause Mortality
OFC (SPII) OFC (SPIII) OFC (SPIV) Flu (SPIV)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
OFC (SPII) OFC (SPIII) OFC (SPIV) Flu (SPIV)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/892 (1.46%)      9/655 (1.37%)      9/221 (4.07%)      7/223 (3.14%)    
Cardiac disorders         
Acute myocardial infarction  1  1/892 (0.11%)  1 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
General disorders         
Chest pain  1  0/892 (0.00%)  0 0/655 (0.00%)  0 0/221 (0.00%)  0 1/223 (0.45%)  1
Device failure  1  1/892 (0.11%)  1 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
Hepatobiliary disorders         
Cholelithiasis  1  0/892 (0.00%)  0 0/655 (0.00%)  0 1/221 (0.45%)  1 0/223 (0.00%)  0
Infections and infestations         
Abscess limb  1  1/892 (0.11%)  1 1/655 (0.15%)  1 0/221 (0.00%)  0 1/223 (0.45%)  1
Cellulitis  1  1/892 (0.11%)  1 1/655 (0.15%)  1 1/221 (0.45%)  1 0/223 (0.00%)  0
Pilonidal cyst  1  1/892 (0.11%)  1 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
Injury, poisoning and procedural complications         
Overdose  1  2/892 (0.22%)  2 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
Metabolism and nutrition disorders         
Hypokalaemia  1  0/892 (0.00%)  0 0/655 (0.00%)  0 0/221 (0.00%)  0 1/223 (0.45%)  1
Hyponatraemia  1  0/892 (0.00%)  0 0/655 (0.00%)  0 0/221 (0.00%)  0 1/223 (0.45%)  1
Musculoskeletal and connective tissue disorders         
Osteonecrosis  1  0/892 (0.00%)  0 1/655 (0.15%)  1 0/221 (0.00%)  0 0/223 (0.00%)  0
Pain in extremity  1  1/892 (0.11%)  1 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Metastatic neoplasm  1 [1]  0/892 (0.00%)  0 0/655 (0.00%)  0 1/221 (0.45%)  1 0/223 (0.00%)  0
Nervous system disorders         
Headache  1  1/892 (0.11%)  4 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
Syncope  1  1/892 (0.11%)  1 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
Psychiatric disorders         
Aggression  1  0/892 (0.00%)  0 0/655 (0.00%)  0 1/221 (0.45%)  1 0/223 (0.00%)  0
Anxiety  1  3/892 (0.34%)  3 2/655 (0.31%)  2 0/221 (0.00%)  0 1/223 (0.45%)  1
Confusional state  1  0/892 (0.00%)  0 0/655 (0.00%)  0 0/221 (0.00%)  0 1/223 (0.45%)  1
Depression  1  1/892 (0.11%)  1 1/655 (0.15%)  1 3/221 (1.36%)  3 3/223 (1.35%)  3
Homicidal ideation  1  0/892 (0.00%)  0 0/655 (0.00%)  0 1/221 (0.45%)  1 0/223 (0.00%)  0
Major depression  1  0/892 (0.00%)  0 1/655 (0.15%)  1 0/221 (0.00%)  0 0/223 (0.00%)  0
Suicidal ideation  1  1/892 (0.11%)  1 1/655 (0.15%)  1 1/221 (0.45%)  1 0/223 (0.00%)  0
Suicide attempt  1  2/892 (0.22%)  2 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Haemoptysis  1  0/892 (0.00%)  0 0/655 (0.00%)  0 1/221 (0.45%)  1 0/223 (0.00%)  0
Surgical and medical procedures         
Hip arthroplasty  1  0/892 (0.00%)  0 0/655 (0.00%)  0 0/221 (0.00%)  0 1/223 (0.45%)  1
Vascular disorders         
Hypertensive crisis  1  0/892 (0.00%)  0 1/655 (0.15%)  1 0/221 (0.00%)  0 0/223 (0.00%)  0
Thrombophlebitis superficial  1  0/892 (0.00%)  0 0/655 (0.00%)  0 1/221 (0.45%)  1 0/223 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
[1]
Event resulted in death
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
OFC (SPII) OFC (SPIII) OFC (SPIV) Flu (SPIV)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   606/892 (67.94%)      348/655 (53.13%)      100/221 (45.25%)      105/223 (47.09%)    
Gastrointestinal disorders         
Constipation  1  24/892 (2.69%)  25 3/655 (0.46%)  3 0/221 (0.00%)  0 0/223 (0.00%)  0
Diarrhoea  1  20/892 (2.24%)  20 5/655 (0.76%)  5 5/221 (2.26%)  5 6/223 (2.69%)  7
Dry mouth  1  125/892 (14.01%)  129 8/655 (1.22%)  8 0/221 (0.00%)  0 1/223 (0.45%)  1
Dyspepsia  1  15/892 (1.68%)  17 7/655 (1.07%)  7 2/221 (0.90%)  2 3/223 (1.35%)  3
Nausea  1  34/892 (3.81%)  37 18/655 (2.75%)  19 10/221 (4.52%)  10 8/223 (3.59%)  9
Vomiting  1  12/892 (1.35%)  12 15/655 (2.29%)  15 6/221 (2.71%)  6 4/223 (1.79%)  5
General disorders         
Fatigue  1  68/892 (7.62%)  74 15/655 (2.29%)  15 2/221 (0.90%)  2 2/223 (0.90%)  2
Irritability  1  12/892 (1.35%)  12 2/655 (0.31%)  2 1/221 (0.45%)  1 1/223 (0.45%)  1
Oedema peripheral  1  32/892 (3.59%)  34 11/655 (1.68%)  12 0/221 (0.00%)  0 0/223 (0.00%)  0
Pain  1  4/892 (0.45%)  5 9/655 (1.37%)  9 2/221 (0.90%)  2 2/223 (0.90%)  2
Pyrexia  1  9/892 (1.01%)  9 10/655 (1.53%)  12 2/221 (0.90%)  2 1/223 (0.45%)  1
Infections and infestations         
Gastroenteritis  1  4/892 (0.45%)  4 6/655 (0.92%)  6 6/221 (2.71%)  7 3/223 (1.35%)  3
Influenza  1  8/892 (0.90%)  8 12/655 (1.83%)  12 3/221 (1.36%)  3 2/223 (0.90%)  2
Nasopharyngitis  1  37/892 (4.15%)  40 23/655 (3.51%)  23 9/221 (4.07%)  12 12/223 (5.38%)  13
Upper respiratory tract infection  1  9/892 (1.01%)  9 20/655 (3.05%)  20 11/221 (4.98%)  22 7/223 (3.14%)  9
Investigations         
Blood creatine phosphokinase increased  1  0/892 (0.00%)  0 3/655 (0.46%)  3 3/221 (1.36%)  3 1/223 (0.45%)  1
Blood glucose increased  1  9/892 (1.01%)  10 4/655 (0.61%)  4 4/221 (1.81%)  4 1/223 (0.45%)  1
Blood prolactin increased  1  0/892 (0.00%)  0 12/655 (1.83%)  12 0/221 (0.00%)  0 0/223 (0.00%)  0
Blood triglycerides increased  1  17/892 (1.91%)  18 15/655 (2.29%)  15 4/221 (1.81%)  4 1/223 (0.45%)  1
Glycosylated haemoglobin increased  1  0/892 (0.00%)  0 3/655 (0.46%)  3 3/221 (1.36%)  3 0/223 (0.00%)  0
Neutrophil count increased  1  1/892 (0.11%)  1 1/655 (0.15%)  1 3/221 (1.36%)  3 0/223 (0.00%)  0
Weight increased  1  151/892 (16.93%)  155 59/655 (9.01%)  60 8/221 (3.62%)  8 5/223 (2.24%)  5
White blood cell count increased  1  1/892 (0.11%)  1 1/655 (0.15%)  1 3/221 (1.36%)  3 0/223 (0.00%)  0
Metabolism and nutrition disorders         
Decreased appetite  1  9/892 (1.01%)  9 0/655 (0.00%)  0 1/221 (0.45%)  1 4/223 (1.79%)  4
Hypercholesterolaemia  1  1/892 (0.11%)  1 4/655 (0.61%)  4 3/221 (1.36%)  3 0/223 (0.00%)  0
Hypertriglyceridaemia  1  2/892 (0.22%)  2 2/655 (0.31%)  2 3/221 (1.36%)  3 0/223 (0.00%)  0
Increased appetite  1  123/892 (13.79%)  129 11/655 (1.68%)  11 3/221 (1.36%)  3 1/223 (0.45%)  1
Musculoskeletal and connective tissue disorders         
Arthralgia  1  11/892 (1.23%)  12 6/655 (0.92%)  7 3/221 (1.36%)  3 0/223 (0.00%)  0
Back pain  1  13/892 (1.46%)  13 9/655 (1.37%)  9 3/221 (1.36%)  3 2/223 (0.90%)  2
Muscle spasms  1  9/892 (1.01%)  10 0/655 (0.00%)  0 0/221 (0.00%)  0 0/223 (0.00%)  0
Neck pain  1  3/892 (0.34%)  4 1/655 (0.15%)  1 1/221 (0.45%)  1 4/223 (1.79%)  4
Nervous system disorders         
Akathisia  1  12/892 (1.35%)  12 9/655 (1.37%)  9 0/221 (0.00%)  0 0/223 (0.00%)  0
Disturbance in attention  1  13/892 (1.46%)  13 2/655 (0.31%)  2 0/221 (0.00%)  0 0/223 (0.00%)  0
Dizziness  1  29/892 (3.25%)  31 6/655 (0.92%)  6 0/221 (0.00%)  0 3/223 (1.35%)  3
Headache  1  64/892 (7.17%)  76 39/655 (5.95%)  55 15/221 (6.79%)  60 13/223 (5.83%)  24
Hypersomnia  1  12/892 (1.35%)  12 6/655 (0.92%)  6 2/221 (0.90%)  2 1/223 (0.45%)  1
Lethargy  1  10/892 (1.12%)  10 0/655 (0.00%)  0 1/221 (0.45%)  1 0/223 (0.00%)  0
Restless legs syndrome  1  9/892 (1.01%)  9 1/655 (0.15%)  1 1/221 (0.45%)  1 1/223 (0.45%)  1
Sedation  1  61/892 (6.84%)  66 17/655 (2.60%)  20 3/221 (1.36%)  5 0/223 (0.00%)  0
Somnolence  1  76/892 (8.52%)  82 20/655 (3.05%)  21 1/221 (0.45%)  1 3/223 (1.35%)  3
Tremor  1  33/892 (3.70%)  34 10/655 (1.53%)  11 1/221 (0.45%)  1 2/223 (0.90%)  2
Psychiatric disorders         
Anxiety  1  21/892 (2.35%)  23 12/655 (1.83%)  12 2/221 (0.90%)  2 9/223 (4.04%)  9
Depression  1  2/892 (0.22%)  2 4/655 (0.61%)  4 2/221 (0.90%)  2 12/223 (5.38%)  12
Initial insomnia  1  10/892 (1.12%)  18 7/655 (1.07%)  8 1/221 (0.45%)  1 1/223 (0.45%)  1
Insomnia  1  20/892 (2.24%)  24 16/655 (2.44%)  17 8/221 (3.62%)  11 16/223 (7.17%)  26
Libido decreased  1  14/892 (1.57%)  14 6/655 (0.92%)  6 0/221 (0.00%)  0 0/223 (0.00%)  0
Restlessness  1  22/892 (2.47%)  24 7/655 (1.07%)  7 1/221 (0.45%)  1 0/223 (0.00%)  0
Reproductive system and breast disorders         
Prostatomegaly  1  0/892 (0.00%)  0 0/655 (0.00%)  0 1/78 (1.28%)  1 0/70 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Epistaxis  1  9/892 (1.01%)  9 1/655 (0.15%)  1 0/221 (0.00%)  0 0/223 (0.00%)  0
Vascular disorders         
Hypertension  1  9/892 (1.01%)  9 5/655 (0.76%)  5 2/221 (0.90%)  2 0/223 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00958568     History of Changes
Other Study ID Numbers: 12115
H6P-MC-HDAY ( Other Identifier: Eli Lilly and Company )
CTRI/2009/091/000654 ( Registry Identifier: Clinical Trials Register India )
First Submitted: August 12, 2009
First Posted: August 13, 2009
Results First Submitted: March 22, 2013
Results First Posted: April 1, 2014
Last Update Posted: April 1, 2014