A Study Comparing the Efficacy and Safety of Duloxetine and Placebo for the Treatment of Depression in Elderly Patients

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00406848
First received: November 29, 2006
Last updated: September 13, 2010
Last verified: September 2010
Results First Received: July 22, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: duloxetine hydrochloride
Drug: placebo

  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
This study had a double-blind one-week placebo lead-in period before randomization, so baseline is defined as Week 1. 370 total patients were randomized and make up the safety analysis population. 299 of these patients were randomized under protocol amendments c, d and e, and make up the efficacy analysis population.

Reporting Groups
  Description
Duloxetine Participants received placebo for 1 week (double-blind placebo lead-in) then started with duloxetine 30 milligrams (mg) orally once daily (QD) for 1 week, followed by duloxetine 60 mg QD orally for 11 weeks. This double-blind acute treatment phase was followed by a double-blind 12 week continuation phase during which participants either remained on 60 mg QD or were eligible for dose escalation to 120 mg QD orally based on depression symptom severity.
Placebo Participants received placebo for 13 weeks (The first week was placebo lead-in). This double-blind acute phase was followed by a double-blind 12 week continuation phase during which participants either remained on placebo or were eligible for receiving duloxetine 60 milligrams (mg) orally once daily (QD), beginning with duloxetine 30 mg QD orally for 1 week followed by duloxetine 60 mg QD orally for the remainder of the study based on depression symptom severity.

Participant Flow:   Overall Study
    Duloxetine     Placebo  
STARTED     249 [1]   121 [2]
COMPLETED     156     67  
NOT COMPLETED     93     54  
Withdrawal by Subject                 27                 22  
Adverse Event                 38                 7  
Lack of Efficacy                 9                 14  
Protocol Violation                 10                 6  
Lost to Follow-up                 6                 2  
Physician Decision                 2                 2  
Sponsor Decision                 1                 1  
[1] Represents full safety analysis population. Efficacy analysis population (c,d,e) N=204.
[2] Represents full safety analysis population. Efficacy analysis population (c,d,e) N=95.



  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 placebo for 1 week (double-blind placebo lead-in) then started with duloxetine 30 milligrams (mg) orally once daily (QD) for 1 week, followed by duloxetine 60 mg QD orally for 11 weeks. This double-blind acute treatment phase was followed by a double-blind 12 week continuation phase during which participants either remained on 60 mg QD or were eligible for dose escalation to 120 mg QD orally based on depression symptom severity.
Placebo Participants received placebo for 13 weeks (The first week was placebo lead-in). This double-blind acute phase was followed by a double-blind 12 week continuation phase during which participants either remained on placebo or were eligible for receiving duloxetine 60 milligrams (mg) orally once daily (QD), beginning with duloxetine 30 mg QD orally for 1 week followed by duloxetine 60 mg QD orally for the remainder of the study based on depression symptom severity.
Total Total of all reporting groups

Baseline Measures
    Duloxetine     Placebo     Total  
Number of Participants  
[units: participants]
  249     121     370  
Age  
[units: years]
Mean ± Standard Deviation
  72.89  ± 6.10     73.02  ± 5.64     72.93  ± 5.95  
Gender  
[units: participants]
     
Female     163     71     234  
Male     86     50     136  
Race/Ethnicity, Customized  
[units: Participants]
     
African     5     6     11  
Caucasian     198     92     290  
Hispanic     46     22     68  
Native American     0     1     1  
Region of Enrollment  
[units: participants]
     
France     13     8     21  
United States     195     94     289  
Mexico     17     8     25  
Puerto Rico     24     11     35  
17 item Hamilton Depression Rating Scale Total Score(HAMD-17) [1]
[units: units on a scale]
Mean ± Standard Deviation
  19.42  ± 5.56     19.32  ± 5.78     19.39  ± 5.62  
17 item Hamilton Depression Rating Scale (HAMD-17) - Maier subscale [2]
[units: Units on a scale]
Mean ± Standard Deviation
  9.96  ± 3.11     10.08  ± 3.36     10.00  ± 3.19  
Geriatric Depression Scale (GDS) Total Score [3]
[units: units on a scale]
Mean ± Standard Deviation
  18.54  ± 6.91     17.64  ± 6.66     18.26  ± 6.83  
Numerical Rating Scale (NRS) Overall Pain Score [4]
[units: units on a scale]
Mean ± Standard Deviation
  3.79  ± 2.96     3.59  ± 2.67     3.73  ± 2.87  
Brief Pain Inventory (BPI) 24-hour Average Pain Score [5]
[units: units on a scale]
Mean ± Standard Deviation
  3.48  ± 2.70     3.48  ± 2.57     3.48  ± 2.66  
Mini Mental State Exam (MMSE) Total Score [6]
[units: units on a scale]
Mean ± Standard Deviation
  28.55  ± 1.83     28.42  ± 1.72     28.51  ± 1.79  
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [7]
[units: units on a scale]
Mean ± Standard Deviation
  29.25  ± 5.57     28.46  ± 5.40     29.00  ± 5.52  
[1] The 17-item HAMD 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). Results shown are based on efficacy analysis population only.
[2] The Maier subscale (Items 1,2,7,8,9,10) represents symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Results shown are based on efficacy analysis population only.
[3] The 30-item Geriatric Depression Scale (GDS) is a self-administered test of 30 questions to measure the severity of depression. The yes/no questions result in a range of scores from 0 (normal) to 30 (severe depression). Results shown are based on efficacy analysis population only.
[4] How much the participant has been bothered by pain over the last week, as measured by an 11-point Likert scale. A score of 0 reflects "not bothered at all" and a score of 10 reflects "extremely bothered". Results shown are based on efficacy analysis population only.
[5] A self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Results shown are based on efficacy analysis population only.
[6] Mini-Mental State Examination (MMSE)is a widely used rating measure of cognitive ability. The MMSE will be used to categorize patients as with or without dementia. Patients with a MMSE score of 20 to 23 will be categorized as having mild dementia, while those with a score of ≥ 24 will be categorized as having no dementia. Scores range from 0 to 30. Results shown are based on efficacy analysis population only.
[7] 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). Results shown are based on efficacy analysis population only.



  Outcome Measures
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1.  Primary:   Change From Baseline to 13 Weeks in Hamilton Depression Rating Scale (HAMD-17) Maier Subscale   [ Time Frame: baseline (Week 1), Week 13 ]

2.  Secondary:   Change From Baseline on the 30-item Geriatric Depression Scale (GDS)   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

3.  Secondary:   Change From Baseline in the HAMD-17 Total Score, Subscales, and Individual Items   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

4.  Secondary:   Change From Baseline in the Brief Pain Inventory (BPI) Severity and Interference Scores   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

5.  Secondary:   Change From Baseline in the Numeric Rating Scales (NRS) for Pain Item Scores   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

6.  Secondary:   Patient's Global Impression of Improvement (PGI-I) at 13 Weeks and 25 Weeks   [ Time Frame: Week 13, Week 25 ]

7.  Secondary:   Change From Baseline in the Clinical Global Impression-Severity (CGI-S)   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

8.  Secondary:   Change From Baseline in the Mini-Mental State Exam (MMSE)   [ Time Frame: baseline (Week 1), Week 9, Week 25 ]

9.  Secondary:   Change From Baseline in the Quality of Life, Enjoyment, and Satisfaction Questionnaire (Q-LES-Q-SF)   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

10.  Secondary:   Probability of Remission as Measured by the HAMD-17 Total Score ≤7 and ≤10   [ Time Frame: Week 13, Week 25 ]

11.  Secondary:   Probability of Response at Endpoint as Measured by ≥50% Improvement in the HAMD-17 Total Score   [ Time Frame: Week 13, Week 25 ]

12.  Secondary:   Probability of Remission as Measured by the HAMD-17 Total Score ≤7 and ≤10 by Medical Comorbidity Severity as Assessed by the Cumulative Illness Rating Scale-Geriatric Version (CIRS-G)   [ Time Frame: Week 13, Week 25 ]

13.  Secondary:   Probability of Efficacy Onset as Measured by at Least 20% Sustained Reduction From Baseline in the HAMD-17 Maier Subscale at Week 3   [ Time Frame: Week 3 ]

14.  Secondary:   Change From Baseline in Supine Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

15.  Secondary:   Change From Baseline in Pulse Rate   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

16.  Secondary:   Change From Baseline in Weight   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

17.  Secondary:   Number of Participants With Abnormal Vital Signs and Weight at Any Time During the Study   [ Time Frame: Baseline (Week 1) through Week 25 ]

18.  Secondary:   Number of Participants Experiencing Sustained Hypertension (SH) or Orthostatic Hypotension (OH)   [ Time Frame: baseline (Week 1) through Week 25 ]

19.  Secondary:   Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation   [ Time Frame: baseline (Week 1) through Week 25 ]

20.  Secondary:   Change From Baseline in Laboratory Values - Platelet Count   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

21.  Secondary:   Change From Baseline in Laboratory Values - Uric Acid   [ Time Frame: baseline (Week 1), Week 13, Week 25 ]

22.  Secondary:   Change From Baseline in Laboratory Values - Erythrocyte Count   [ Time Frame: baseline (Week 1), Week 25 ]

23.  Secondary:   Change From Baseline in Laboratory Values - Hemoglobin, Mean Cell Hemoglobin Concentration (MCHC)   [ Time Frame: baseline (Week 1), Week 25 ]

24.  Secondary:   Change From Baseline in Laboratory Values - Chloride and Fasting Glucose   [ Time Frame: baseline (Week 1), Week 25 ]

25.  Secondary:   Number of Participants With Abnormal Laboratory Values - Low Leukocyte Count   [ Time Frame: baseline (Week 1) through Week 13 ]

26.  Secondary:   Change From Baseline in Electrocardiograms   [ Time Frame: baseline (Week 1), Week 25 ]

27.  Secondary:   Number of Participants With Successful Treatment Outcome   [ Time Frame: Baseline (Week 1) through Week 25 ]

28.  Secondary:   Change From Baseline on Cognitive Test Scores: Verbal Learning and Recall Test (VLRT), Symbol Digit Substitution Test (SDST), Trail Making Test (Part B), 2-Digit Cancellation Test (2DCT), and the Composite Cognitive Score Derived From the Above Scores   [ Time Frame: baseline (Week 1), Week 9, Week 25 ]


  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


No publications provided by Eli Lilly and Company

Publications automatically indexed to this study:

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00406848     History of Changes
Other Study ID Numbers: 10815, F1J-US-HMFA
Study First Received: November 29, 2006
Results First Received: July 22, 2010
Last Updated: September 13, 2010
Health Authority: United States: Food and Drug Administration