A Study of Patients With Major Depressive Disorder and Residual Apathy

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00985504
First received: September 25, 2009
Last updated: December 7, 2011
Last verified: August 2011
Results First Received: August 29, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: Duloxetine
Drug: Escitalopram

  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

Acute treatment period (1 week): Participants randomized to switch to 60 milligrams (mg) duloxetine once daily (QD) by mouth (po) or 10 mg escitalopram QD po.

Optimization period (7 weeks): Participants given duloxetine or escitalopram in acute study period may optimize their QD po doses (60-120 mg duloxetine QD po; 10-20 mg escitalopram QD po).


Reporting Groups
  Description
Duloxetine Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Escitalopram Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.

Participant Flow for 2 periods

Period 1:   Acute Treatment Period
    Duloxetine     Escitalopram  
STARTED     244     239  
COMPLETED     229     227  
NOT COMPLETED     15     12  
Adverse Event                 3                 4  
Entry Criteria Not Met                 1                 2  
Protocol Violation                 2                 0  
Sponsor Decision                 0                 1  
Withdrawal by Subject                 9                 5  

Period 2:   Optimization Period
    Duloxetine     Escitalopram  
STARTED     229     227  
COMPLETED     203     204  
NOT COMPLETED     26     23  
Adverse Event                 7                 9  
Death                 0                 1  
Lack of Efficacy                 5                 3  
Lost to Follow-up                 0                 1  
Physician Decision                 1                 0  
Protocol Violation                 3                 1  
Withdrawal by Subject                 10                 8  



  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
Duloxetine Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Escitalopram Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Total Total of all reporting groups

Baseline Measures
    Duloxetine     Escitalopram     Total  
Number of Participants  
[units: participants]
  244     239     483  
Age  
[units: years]
Mean ± Standard Deviation
  44.15  ± 13.81     44.93  ± 12.89     44.54  ± 13.35  
Gender  
[units: participants]
     
Female     187     179     366  
Male     57     60     117  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     45     44     89  
Not Hispanic or Latino     199     195     394  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB) [1]
[units: participants]
     
American Indian or Alaska Native     34     37     71  
Asian     90     82     172  
Native Hawaiian or Other Pacific Islander     1     0     1  
Black or African American     0     1     1  
White     120     119     239  
More than one race     1     0     1  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
     
Australia     24     25     49  
Canada     44     43     87  
China     47     41     88  
Italy     23     22     45  
Korea, Republic of     18     15     33  
Mexico     42     43     85  
Russian Federation     23     25     48  
Taiwan     23     25     48  
Taking Escitalopram 3 Months Prior to Study Entry [2]
[units: participants]
     
Yes     67     59     126  
No     177     180     357  
Apathy Evaluation Scale - Clinician Rated Version (AES-C) Total Score [3]
[units: units on a scale]
Mean ± Standard Deviation
  46.28  ± 7.82     46.34  ± 8.14     46.31  ± 7.97  
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [4]
[units: units on a scale]
Mean ± Standard Deviation
  10.57  ± 3.49     10.29  ± 3.68     10.43  ± 3.59  
Montgomery-Asberg Depression Rating Scale (MADRS) Item 8 Score [5]
[units: units on a scale]
Mean ± Standard Deviation
  1.82  ± 1.10     1.82  ± 1.15     1.82  ± 1.13  
Clinical Global Impressions of Severity Scale (CGI-S) [6]
[units: units on a scale]
Mean ± Standard Deviation
  3.05  ± 0.91     3.04  ± 0.91     3.05  ± 0.91  
Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total Score [7]
[units: units on a scale]
Mean ± Standard Deviation
  10.72  ± 4.92     10.51  ± 4.95     10.62  ± 4.93  
The Massachusetts General Hospital Cognitive and Physical functioning Questionnaire (MGH-CPFQ) Total [8]
[units: units on a scale]
Mean ± Standard Deviation
  24.78  ± 5.73     24.69  ± 5.83     24.73  ± 5.78  
Sheehan Disability Scale - Total Score (SDS Total) [9]
[units: units on a scale]
Mean ± Standard Deviation
  15.32  ± 6.76     14.62  ± 6.39     14.98  ± 6.58  
[1] One participant selected 2 races. Therefore, the total number of participants in the race category will be larger than the number of participants in the baseline table.
[2] Previous therapy status is defined as the number of participants who had taken escitalopram 3 months prior to study entry.
[3] The AES-C is a validated 18-item instrument used to assess cognitive, behavioral, emotional and other symptoms of apathy. Clinicians rate each item based on verbal and nonverbal information provided by the participant. Item scores range from 1 (not at all characteristic) to 4 (a lot characteristic). Total scores range from 18 to 72 where higher derived scores indicate more severe apathy.
[4] The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
[5] The MADRS Item 8 assesses participants' inability to feel, through evaluation of their interest in their surroundings or activities that normally give pleasure, as well as their ability to react with adequate emotion to circumstances or people. The score ranges from 0 (normal interest in the surroundings and in other people) to 6 (the experience of being emotionally paralyzed, inability to feel anger, grief or pleasure and a complete or even painful failure to feel for close relatives and friends).
[6] The 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).
[7] RSAT assesses symptoms of apathy or decreased motivation among depressed participants who have achieved symptomatic remission with antidepressant treatment and consists of 6 self-report items assessing energy level, motivation and interest, cognitive functioning, weight gain, sleep and sexual functioning, as well as affect. Each item score ranges from 0 to 4 with total scores ranging from 0 to 28. Higher scores indicate greater disease severity.
[8] The MGH-CPFQ is a 7-item participant-rated questionnaire evaluating the participant's cognitive and physical well-being during the past month. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each of the 7 items is scored on a 6-point scale ranging from "greater than normal" (score of 1) to "normal" (score of 2), to "totally absent" (score of 6). Total scores range from 7 to 42. Higher scores indicate greater disease severity.
[9] The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in the Apathy Evaluation Scale - Clinician Rated Version (AES-C) Total Score at Week 8   [ Time Frame: Baseline, 8 weeks ]

2.  Secondary:   Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8   [ Time Frame: Baseline, 8 weeks ]

3.  Secondary:   Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8   [ Time Frame: Baseline, 8 weeks ]

4.  Secondary:   Patient’s Global Impressions of Improvement Scale (PGI-I) Rating Scale Score at Week 8   [ Time Frame: 8 weeks ]

5.  Secondary:   Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Rating Scale at Week 8   [ Time Frame: Baseline, 8 weeks ]

6.  Secondary:   Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Item 8 (Inability to Feel) at Week 8   [ Time Frame: Baseline, 8 weeks ]

7.  Secondary:   Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8   [ Time Frame: Baseline, 8 weeks ]

8.  Secondary:   Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8   [ Time Frame: Baseline, 8 weeks ]

9.  Secondary:   Percentage of Participants Who Relapsed During 8 Weeks   [ Time Frame: Baseline through 8 weeks ]

10.  Secondary:   Number of Days From Baseline to Relapse as Defined by Montgomery-Asberg Depression Rating Scale (MADRS) Total Score ≥16 During 8 Weeks   [ Time Frame: Baseline through 8 weeks ]

11.  Secondary:   Percentage of Participants Who Discontinue Due to Lack of Efficacy During 8 Weeks   [ Time Frame: Baseline through 8 weeks ]


  Serious Adverse Events


  Other Adverse Events


  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.


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
No text entered.  


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: NCT00985504     History of Changes
Other Study ID Numbers: 13018, F1J-CR-HMGM
Study First Received: September 25, 2009
Results First Received: August 29, 2011
Last Updated: December 7, 2011
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Brazil: Ministry of Health
Canada: Canadian Institutes of Health Research
China: Food and Drug Administration
Italy: National Bioethics Committee
Italy: The Italian Medicines Agency
South Korea: Korea Food and Drug Administration (KFDA)
Mexico: Federal Commission for Sanitary Risks Protection
Russia: Ministry of Health of the Russian Federation
Taiwan: National Bureau of Controlled Drugs