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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
History of Changes
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
  Hide Baseline Characteristics

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  
Number of Participants  
[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  
17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Score [2]
[units: units on a scale]
Mean ± Standard Deviation 		  7.7  ± 2.1     8.0  ± 2.0     7.4  ± 1.7     7.8  ± 2.0  
17-Item Hamilton Depression Rating Scale (HAMD-17) Core Score [3]
[units: units on a scale]
Mean ± Standard Deviation 		  8.1  ± 2.6     9.0  ± 2.6     7.9  ± 2.8     8.4  ± 2.7  
17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Score [4]
[units: units on a scale]
Mean ± Standard Deviation 		  10.7  ± 2.6     11.7  ± 2.6     10.0  ± 2.7     11.0  ± 2.7  
17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation Score [5]
[units: units on a scale]
Mean ± Standard Deviation 		  7.1  ± 2.1     8.2  ± 1.9     7.2  ± 2.4     7.5  ± 2.1  
17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Score [6]
[units: units on a scale]
Mean ± Standard Deviation 		  3.1  ± 1.6     3.4  ± 1.4     3.2  ± 1.7     3.2  ± 1.5  
17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score [7]
[units: units on a scale]
Mean ± Standard Deviation 		  21.3  ± 4.5     23.3  ± 4.5     20.7  ± 4.5     21.9  ± 4.6  
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 [8]
[units: Units on a scale]
Mean ± Standard Deviation 		  4.7  ± 1.9     5.0  ± 2.0     4.4  ± 2.2     4.8  ± 2.0  
Brief Pain Inventory - Short Form Interference Score [9]
[units: Units on a scale]
Mean ± Standard Deviation 		  5.2  ± 1.6     5.9  ± 1.8     5.2  ± 1.9     5.5  ± 1.8  
Changes in Sexual Function Questionnaire (CSFQ) [10]
[units: Units on a scale]
Mean ± Standard Deviation 		  35.3  ± 10.3     35.4  ± 9.8     33.8  ± 9.4     35.1  ± 10.0  
Clinical Global Impressions - Severity (CGI-Severity) Score [11]
[units: Units on a scale]
Mean ± Standard Deviation 		  4.2  ± 0.6     4.4  ± 0.6     4.3  ± 0.7     4.3  ± 0.6  
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 [12]
[units: Units on a scale]
Mean ± Standard Deviation 		  17.9  ± 6.8     21.4  ± 6.8     17.9  ± 7.6     19.2  ± 7.1  
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) [13]
[units: Units on a scale]
Mean ± Standard Deviation 		  5.4  ± 2.9     6.3  ± 3.0     5.5  ± 3.0     5.7  ± 3.0  
Treatment Satisfaction Questionnaire for Medication (TSQM) [14]
[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] Previous selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) treatment.
[2] 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).
[3] The Core subscale (Items 1,2,3,7,8) evaluates "core" symptoms of depression. Total subscale scores range from 0 (normal) to 20 (severe).
[4] 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).
[5] 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).
[6] The Sleep Subscale (Items 4,5,6) evaluates initial, middle, and late insomnia. Total subscale scores range from 0 (no difficulty) to 6 (difficulty).
[7] 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).
[8] 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).
[9] 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).
[10] 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.
[11] 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).
[12] 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.
[13] 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.
[14] 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 ]
  Show Outcome Measure 1

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 ]
  Show Outcome Measure 2

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

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

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

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

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

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

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

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

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 ]
  Hide Outcome Measure 11

Measure Type Secondary
Measure Title Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks
Measure Description 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). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time Frame Baseline, 8 weeks  
Safety Issue No  

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.
Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group "Unclassified" was excluded from statistical testing.

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).

Measured Values
    Duloxetine Responders     Duloxetine Non-Responders  
Number of Participants Analyzed  
[units: participants]
 		  108     85  
Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks  
[units: Units on a scale]
Least Squares Mean ( 95% Confidence Interval ) 		  -2.56  
  ( -3.13 to -1.99 )   		  -2.14  
  ( -2.75 to -1.53 )  


Statistical Analysis 1 for Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks
Groups [1] All groups
Mean Difference (Final Values) [2] -0.42
95% Confidence Interval ( -1.08 to -0.24 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  Least Squares Mean Difference = Responders - Non-Responders.



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

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 ]
  Show Outcome Measure 13

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 ]
  Show Outcome Measure 14

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


  Serious Adverse Events
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  Other Adverse Events
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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.


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: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00696774     History of Changes
Other Study ID Numbers: 12349, F1J-CR-S022
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)