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Switching to Duloxetine in Patients With Depression (ARDENT)

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00696774
First received: June 11, 2008
Last updated: September 2, 2010
Last verified: September 2010
Results First Received: July 15, 2010  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Depressive Disorder, Major
Intervention: Drug: Duloxetine

  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
270 participants began the study. 26 were screen failures (17 did not meet entry criteria, 7 decided to withdraw, and 2 withdrew based on the physician's decision). 2 participants discontinued before enrollment (1 was lost to follow-up and 1 decided to withdraw).

Reporting Groups
  Description
Responders 60 milligram (mg) duloxetine capsules, once daily (QD), for 4 weeks (Study Period II). Responder group - 60 mg capsules, QD, for 4 weeks more (Study Period III).
Non-Responders 60 mg duloxetine capsules, QD, for 4 weeks (Study Period II). Non-Responder group - 120 mg capsules, QD, for 4 weeks more (Study Period III).
Unclassified Participants who received 60 milligram (mg) duloxetine capsules, once daily (QD), for 4 weeks (Study Period II) with unknown response status.

Participant Flow for 2 periods

Period 1:   Period II
    Responders   Non-Responders   Unclassified
STARTED   115   91   36 [1] 
COMPLETED   115   91   0 
NOT COMPLETED   0   0   36 
Adverse Event                0                0                15 
Lost to Follow-up                0                0                4 
Protocol Violation                0                0                11 
Withdrawal by Subject                0                0                4 
Sponsor Decision                0                0                0 
Lack of Efficacy                0                0                2 
[1] 1 participant did not receive study drug and was not included in the safety analyses.

Period 2:   Period III
    Responders   Non-Responders   Unclassified
STARTED   113 [1]   88 [2]   0 
COMPLETED   106   81 [3]   0 
NOT COMPLETED   7   7   0 
Adverse Event                1                1                0 
Lost to Follow-up                2                1                0 
Protocol Violation                1                1                0 
Withdrawal by Subject                1                2                0 
Sponsor Decision                2                0                0 
Lack of Efficacy                0                2                0 
[1] 115 reported at Week 4; 113 started Period 3 (1 lost to follow-up and 1 protocol violation).
[2] 91 reported at Week 4; 88 start Period 3 (1 adverse event, 1 protocol violation, 1 lack of efficacy)
[3] 82 participants were reported at Week 8; 81 completed Week 8 as 1 participant decided to withdraw.



  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 Responders 60 milligram (mg) duloxetine capsules, once daily (QD), for 4 weeks (Study Period II). Responder group - 60 mg capsules, QD, for 4 weeks more (Study Period III).
Duloxetine Non-Responders 60 mg duloxetine capsules, QD, for 4 weeks (Study Period II). Non-responder group - 120 mg capsules, QD, for 4 weeks more (Study Period III).
Unclassified Participants who received 60 milligram (mg) duloxetine capsules, once daily (QD), for 4 weeks (Study Period II) with unknown response status.
Total Total of all reporting groups

Baseline Measures
   Duloxetine Responders   Duloxetine Non-Responders   Unclassified   Total 
Overall Participants Analyzed 
[Units: Participants]
 115   91   36   242 
Age 
[Units: Years]
Mean (Standard Deviation)
 43.5  (12.9)   45.6  (12.5)   47.4  (10.6)   44.9  (12.5) 
Gender 
[Units: Participants]
       
Female   88   64   30   182 
Male   27   27   6   60 
Race/Ethnicity, Customized 
[Units: Participants]
       
Caucasian   67   66   17   150 
East Asian   43   23   12   78 
African   1   0   2   3 
Hispanic   2   2   3   7 
West Asian   2   0   2   4 
Region of Enrollment 
[Units: Participants]
       
Korea, Republic of   18   11   9   38 
Brazil   9   11   13   33 
China   25   13   3   41 
Canada   63   56   11   130 
Had Major Depressive Disorder (MDD) Hospitalizations in the Past 24 Months 
[Units: Participants]
       
Yes   8   5   2   15 
No   107   86   34   227 
Had Previous MDD in the Past 24 Months 
[Units: Participants]
       
Yes   79   54   24   157 
No   36   37   12   85 
Had at Least One Historical Illness 
[Units: Participants]
       
Yes   44   32   15   91 
No   71   59   21   151 
Previous Treatment [1] 
[Units: Participants]
       
SSRI   83   69   25   177 
SNRI   31   21   9   61 
Missing or Unknown   1   1   2   4 
[1] Previous selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) treatment.
17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 7.7  (2.1)   8.0  (2.0)   7.4  (1.7)   7.8  (2.0) 
[1] The Anxiety/Somatization Subscale (Items 10-13, 15, 17) evaluates severity of psychic and somatic manifestations of anxiety as well as agitation. Total subscale scores range from 0 (normal) to 18 (severe).
17-Item Hamilton Depression Rating Scale (HAMD-17) Core Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 8.1  (2.6)   9.0  (2.6)   7.9  (2.8)   8.4  (2.7) 
[1] The Core subscale (Items 1,2,3,7,8) evaluates "core" symptoms of depression. Total subscale scores range from 0 (normal) to 20 (severe).
17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 10.7  (2.6)   11.7  (2.6)   10.0  (2.7)   11.0  (2.7) 
[1] The Maier subscale (Items 1,2,7,8,9,10) represents the "core" symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe).
17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 7.1  (2.1)   8.2  (1.9)   7.2  (2.4)   7.5  (2.1) 
[1] The Retardation Subscale (Items 1,7,8,14) evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation. Total subscale scores range from 0 (normal) to 14 (severe).
17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 3.1  (1.6)   3.4  (1.4)   3.2  (1.7)   3.2  (1.5) 
[1] The Sleep Subscale (Items 4,5,6) evaluates initial, middle, and late insomnia. Total subscale scores range from 0 (no difficulty) to 6 (difficulty).
17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 21.3  (4.5)   23.3  (4.5)   20.7  (4.5)   21.9  (4.6) 
[1] The HAMD-17 measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Age of First Episode of MDD 
[Units: Years]
Mean (Standard Deviation)
 35.2  (11.7)   33.5  (13.6)   36.9  (12.8)   34.8  (12.6) 
Brief Pain Inventory - Short Form (BPI-SF) Average Pain Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 4.7  (1.9)   5.0  (2.0)   4.4  (2.2)   4.8  (2.0) 
[1] A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Brief Pain Inventory - Short Form Interference Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 5.2  (1.6)   5.9  (1.8)   5.2  (1.9)   5.5  (1.8) 
[1] The BPI-SF interference score asks about the degree to which pain interferes with mood, walking and other physical activity, work, social activity, relations with others, and sleep. BPI-SF interference score ranges from 0 (no interference) to 10 (interferes completely).
Changes in Sexual Function Questionnaire (CSFQ) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 35.3  (10.3)   35.4  (9.8)   33.8  (9.4)   35.1  (10.0) 
[1] A 14-item patient-rated scale designed to assess medication-related changes in sexual activity/functioning. Items are rated from 1 (never, low enjoyment or pleasure) to 5 (every day/great enjoyment or pleasure). CSFQ measures 5 dimensions of sexual behavior: pleasure; desire/frequency; desire/interest; arousal; orgasm. CSFQ total score is obtained across all 5 dimensions. Lower scores are associated with sexual dysfunction/diminished sexual functioning. Total scores <=47 (men) and <=41 (women) indicate global sexual dysfunction, with all phases of the sexual response cycle being affected.
Clinical Global Impressions - Severity (CGI-Severity) Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 4.2  (0.6)   4.4  (0.6)   4.3  (0.7)   4.3  (0.6) 
[1] 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 patients).
Duration of the Current Episode 
[Units: Days]
Mean (Standard Deviation)
 249.4  (378.3)   264.5  (318.1)   194.1  (182.6)   247.3  (333.3) 
Hamilton Anxiety Rating Scale (HAMA) Total Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 17.9  (6.8)   21.4  (6.8)   17.9  (7.6)   19.2  (7.1) 
[1] The HAMA scale measures anxiety symptoms accompanying major depressive disorder (MDD). Each item of the 14-item HAMA was scored from 0 (not present) to 4 (very severe), with a resulting maximum total score of 56.
Number of MDD Hospitalizations in the Past 24 Months 
[Units: Hospitalizations]
Mean (Standard Deviation)
 1.0  (0.0)   1.0  (0.0)   1.0  (0.0)   1.0  (0.0) 
Number of Previous MDD Episodes in the Past 24 Months 
[Units: MDD episodes]
Mean (Standard Deviation)
 1.6  (0.8)   1.5  (0.7)   1.8  (1.5)   1.6  (0.9) 
Sheehan Disability Scale (SDS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 5.4  (2.9)   6.3  (3.0)   5.5  (3.0)   5.7  (3.0) 
[1] The SDS is completed by the patient and is used to assess the effect of the patient's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life.
Treatment Satisfaction Questionnaire for Medication (TSQM) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 44.2  (17.6)   41.6  (18.2)   47.2  (20.8)   43.7  (18.3) 
[1] The TSQM is a participant-reported measure that best describes how the study medication makes them feel since the last study visit, assessing perceived effectiveness, severity of side effects, and convenience. Convenience, Effectiveness, Side-Effects, and Global Satisfaction scale scores range from 0 (extremely dissatisfied) to 100 (extremely satisfied).


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Brief Pain Inventory-Modified Short Form (BPI-SF) Interference Score Between Responder and Non-Responder Participants at 4 Weeks   [ Time Frame: Baseline, 4 weeks ]

2.  Secondary:   Percentage of Participants Meeting Criteria for Response on the 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale at 4 and 8 Weeks   [ Time Frame: Baseline, 4 weeks, 8 weeks ]

3.  Secondary:   Change From Baseline HAMD-17 Total Score at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

4.  Secondary:   Change From Baseline HAMD-17 Core Subscale at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

5.  Secondary:   Change From Baseline HAMD-17 Maier Subscale at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

6.  Secondary:   Change From Baseline HAMD-17 Anxiety/Somatization Subscale at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

7.  Secondary:   Change From Baseline HAMD-17 Retardation/Somatization Subscale at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

8.  Secondary:   Change From Baseline HAMD-17 Sleep Subscale at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

9.  Secondary:   Change From Baseline in the Hamilton Anxiety Rating Scale (HAMA) at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

10.  Secondary:   Change From Baseline in the Clinical Global Impression – Severity (CGI-Severity) Scale at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

11.  Secondary:   Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks   [ Time Frame: Baseline, 8 weeks ]

12.  Secondary:   Change From Baseline in Patient Global Impression - Improvement (PGI–I) Scale Score at 8 Weeks   [ Time Frame: 8 weeks ]

13.  Secondary:   Change From Baseline in the Sexual Functioning Questionnaire Clinical Version (CSFQ) at 4 and 8 Weeks   [ Time Frame: Baseline, 4 Weeks, 8 weeks ]

14.  Secondary:   Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM) at 4 and 8 Weeks   [ Time Frame: Baseline, 4 weeks, 8 weeks ]

15.  Secondary:   Change From Baseline in the Sheehan Disability Scale (SDS) at 4 and 8 Weeks   [ Time Frame: Baseline, 4 weeks, 8 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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



Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00696774     History of Changes
Other Study ID Numbers: 12349
F1J-CR-S022 ( Other Identifier: Eli Lilly and Company )
Study First Received: June 11, 2008
Results First Received: July 15, 2010
Last Updated: September 2, 2010
Health Authority: Brazil: National Health Surveillance Agency
Canada: Health Canada
China: Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)