A Study in Relapse Prevention of Treatment-Resistant Depression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00958568
First received: August 12, 2009
Last updated: February 17, 2014
Last verified: February 2014
Results First Received: March 22, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Treatment Resistant Depression
Interventions: Drug: Olanzapine and Fluoxetine combination (OFC)
Drug: Fluoxetine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups
  Description
OFC (SPII ) 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.
OFC (SPIII) 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.
OFC (SPIV) 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.
Flu (SPIV) Fluoxetine (Flu): 25 or 50 mg oral, daily, for 27 weeks during double-blind randomized relapse prevention treatment phase (SPIV).

Participant Flow for 3 periods

Period 1:   SPII (Wk 0-8, Acute Open-label)
    OFC (SPII )     OFC (SPIII)     OFC (SPIV)     Flu (SPIV)  
STARTED     892     0     0     0  
COMPLETED     655     0     0     0  
NOT COMPLETED     237     0     0     0  
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 2:   SPIII (Wk 9-20,Open-label Stabilization)
    OFC (SPII )     OFC (SPIII)     OFC (SPIV)     Flu (SPIV)  
STARTED     0     655     0     0  
COMPLETED     0     444     0     0  
NOT COMPLETED     0     211     0     0  
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 3:   SPIV (Wk 21-47, DB Relapse Prevention)
    OFC (SPII )     OFC (SPIII)     OFC (SPIV)     Flu (SPIV)  
STARTED     0     0     221     223  
COMPLETED     0     0     139     117  
NOT COMPLETED     0     0     82     106  
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  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
OFC (SPII-Wk 0-8, Acute Open-label) 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.

Baseline Measures
    OFC (SPII-Wk 0-8, Acute Open-label)  
Number of Participants  
[units: participants]
  892  
Age  
[units: years]
Mean ± Standard Deviation
  44.38  ± 11.98  
Gender  
[units: participants]
 
Female     591  
Male     301  
Ethnicity (NIH/OMB)  
[units: participants]
 
Hispanic or Latino     167  
Not Hispanic or Latino     725  
Unknown or Not Reported     0  
Race (NIH/OMB)  
[units: participants]
 
American Indian or Alaska Native     27  
Asian     115  
Native Hawaiian or Other Pacific Islander     1  
Black or African American     101  
White     634  
More than one race     11  
Unknown or Not Reported     3  
Region of Enrollment  
[units: 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]
[units: kilograms/square meter (kg/m²)]
Mean ± Standard Deviation
  29.12  ± 7.36  
[1] N=892, data was not reported for 1 participant



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to Relapse by Any Criteria   [ Time Frame: Randomization (Week 20) to Week 47 ]

2.  Secondary:   Percentage of Participants Who Relapse by Any Criteria   [ Time Frame: Randomization (Week 20) to Week 47 ]

3.  Secondary:   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   [ Time Frame: Randomization (Week 20) to Week 47 ]

4.  Secondary:   Percentage of Participants Who Relapse as Measured by Hospitalization for Depression or Suicidality   [ Time Frame: Randomization (Week 20) to Week 47 ]

5.  Secondary:   Percentage of Participants Who Relapse as Measured by Discontinuation Due to Lack of Efficacy/Worsening of Depression/Suicidality   [ Time Frame: Randomization (Week 20) to Week 47 ]

6.  Secondary:   Time to Relapse Based on the Montgomery-Åsberg Depression Rating Scale (MADRS) Score With Concomitant Clinical Global Impressions-Severity (CGI-S) of Depression Score   [ Time Frame: Randomization (Week 20) to Week 47 ]

7.  Secondary:   Time to Relapse as Measured by Hospitalization for Depression or Suicidality   [ Time Frame: Randomization (Week 20) to Week 47 ]

8.  Secondary:   Time to Relapse as Measured by Discontinuation Due to Lack of Efficacy/Worsening of Depression/Suicidality   [ Time Frame: Randomization (Week 20) to Week 47 ]

9.  Secondary:   Percentage of Participants Responding to Treatment During Open-Label Acute Treatment Phase   [ Time Frame: Week 0 to Week 8 ]

10.  Secondary:   Percentage of Participants Maintaining Response at Any Point During Stabilization Treatment Phase   [ Time Frame: Week 8 to Week 20 ]

11.  Secondary:   Percentage of Participants Achieving Remission at Any Point During Stabilization Treatment Phase   [ Time Frame: Week 8 to Week 20 ]

12.  Secondary:   Percentage of Participants Maintaining Remission   [ Time Frame: Randomization (Week 20) to Week 47 ]

13.  Secondary:   Mean Change From Week 20 to Week 47 in Montgomery-Asberg Depression Rating Scale (MADRS) Using Mixed-Effects Model Repeated Measures (MMRM) Analysis   [ Time Frame: Randomization (Week 20), Week 47 ]

14.  Secondary:   Mean Change From Week 20 to Week 47 in Montgomery-Asberg Depression Rating Scale (MADRS) Using Last Observation Carried Forward (LOCF) Analysis   [ Time Frame: Randomization (Week 20), up to Week 47 ]

15.  Secondary:   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   [ Time Frame: Randomization (Week 20), Week 47 ]

16.  Secondary:   Resource Utilization - Average Number of Hours Worked for Pay Per Week at Week 47   [ Time Frame: Week 47 ]

17.  Secondary:   Resource Utilization (Number of Psychiatric Visits, Number of Emergency Room or Equivalent Facility Visits for Psychiatric Illness)   [ Time Frame: Randomization (Week 20) to Week 47 ]

18.  Secondary:   Change From Week 20 to Week 47 Endpoint in the Sheehan Disability Scale (SDS)   [ Time Frame: Randomization (Week 20), up to Week 47 ]

19.  Secondary:   Percent of Participants With Treatment-Emergent Akathisia   [ Time Frame: Randomization (Week 20) to Week 47 ]

20.  Secondary:   Percent of Participants With Treatment-Emergent Parkinsonism   [ Time Frame: Randomization (Week 20) to Week 47 ]

21.  Secondary:   Percent of Participants With Treatment-Emergent Dyskinesia   [ Time Frame: Randomization (Week 20) to Week 47 ]

22.  Secondary:   Mean Change From Week 20 to Week 47 in Fasting Total Cholesterol   [ Time Frame: Randomization (Week 20), Week 47 ]

23.  Secondary:   Percent of Participants With Treatment-Emergent High Fasting Total Cholesterol   [ Time Frame: Randomization (Week 20) to Week 47 ]

24.  Secondary:   Mean Change From Week 20 to Week 47 in Fasting Low-Density Lipoprotein (LDL) Cholesterol   [ Time Frame: Randomization (Week 20), Week 47 ]

25.  Secondary:   Percent of Participants With Treatment-Emergent High Fasting Low-Density Lipoprotein (LDL) Cholesterol   [ Time Frame: Randomization (Week 20) to Week 47 ]

26.  Secondary:   Mean Change From Week 20 to Week 47 in Fasting High-Density Lipoprotein (HDL) Cholesterol   [ Time Frame: Randomization (Week 20), Week 47 ]

27.  Secondary:   Percent of Participants With Treatment-Emergent Low Fasting High-Density Lipoprotein (HDL) Cholesterol   [ Time Frame: Randomization (Week 20) to Week 47 ]

28.  Secondary:   Percent of Participants With Treatment-Emergent Hepatic Events   [ Time Frame: Randomization (Week 20) to Week 47 ]

29.  Secondary:   Mean Change From Week 20 to Week 47 in Fasting Triglycerides   [ Time Frame: Randomization (Week 20), Week 47 ]

30.  Secondary:   Percent of Participants With Treatment-Emergent High Fasting Triglycerides   [ Time Frame: Randomization (Week 20) to Week 47 ]

31.  Secondary:   Mean Change From Week 20 to Week 47 in Fasting Glucose   [ Time Frame: Randomization (Week 20), Week 47 ]

32.  Secondary:   Percent of Participants With Treatment-Emergent High Fasting Glucose   [ Time Frame: Randomization (Week 20) to Week 47 ]

33.  Secondary:   Mean Change From Week 20 to Week 47 in Weight   [ Time Frame: Randomization (Week 20), Week 47 ]

34.  Secondary:   Percent of Participants With Week 20-to-Week 47 Endpoint Increase in Weight of at Least 7%   [ Time Frame: Week 20 to Week 47 ]

35.  Secondary:   Percent of Participants With Suicide-Related Thoughts and Behaviors   [ Time Frame: Randomization (Week 20) to Week 47 ]

36.  Secondary:   Mean Change in Corrected (for Rate) Cardiac QT Interval Using Fridericia’s Formula (QTcF) on Electrocardiogram   [ Time Frame: Randomization (Week 20), Week 47 ]

37.  Secondary:   Percent of Participants With Treatment-Emergent Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) on Electrocardiogram ≥500 Milliseconds (Msec)   [ Time Frame: Randomization (Week 20) to Week 47 ]

38.  Secondary:   Percent of Participants With a 60 Milliseconds (Msec) Increase in Fridericia-Corrected (for Rate) Cardiac QT Interval (QTcF) on Electrocardiogram   [ Time Frame: Randomization (Week 20) to Week 47 ]

39.  Other Pre-specified:   Kaplan-Meier Estimate of Percentage of Subjects Not Relapsing at Week 27 (Day 189)   [ Time Frame: Randomization (Week 20) to Week 27 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided


Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00958568     History of Changes
Other Study ID Numbers: 12115, H6P-MC-HDAY, CTRI/2009/091/000654
Study First Received: August 12, 2009
Results First Received: March 22, 2013
Last Updated: February 17, 2014
Health Authority: United States: Food and Drug Administration