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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00406848
Recruitment Status : Completed
First Posted : December 4, 2006
Results First Posted : September 29, 2010
Last Update Posted : September 29, 2010
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by:
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: duloxetine hydrochloride
Drug: placebo
Enrollment 370
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 249 [1] 121 [2]
Completed 156 67
Not Completed 93 54
Reason Not Completed
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.
Arm/Group Title Duloxetine Placebo Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 249 121 370
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 249 participants 121 participants 370 participants
72.89  (6.10) 73.02  (5.64) 72.93  (5.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 249 participants 121 participants 370 participants
Female
163
  65.5%
71
  58.7%
234
  63.2%
Male
86
  34.5%
50
  41.3%
136
  36.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 249 participants 121 participants 370 participants
African 5 6 11
Caucasian 198 92 290
Hispanic 46 22 68
Native American 0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 249 participants 121 participants 370 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] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 249 participants 121 participants 370 participants
19.42  (5.56) 19.32  (5.78) 19.39  (5.62)
[1]
Measure Description: 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.
17 item Hamilton Depression Rating Scale (HAMD-17) - Maier subscale   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 249 participants 121 participants 370 participants
9.96  (3.11) 10.08  (3.36) 10.00  (3.19)
[1]
Measure Description: 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.
Geriatric Depression Scale (GDS) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 249 participants 121 participants 370 participants
18.54  (6.91) 17.64  (6.66) 18.26  (6.83)
[1]
Measure Description: 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.
Numerical Rating Scale (NRS) Overall Pain Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 249 participants 121 participants 370 participants
3.79  (2.96) 3.59  (2.67) 3.73  (2.87)
[1]
Measure Description: 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.
Brief Pain Inventory (BPI) 24-hour Average Pain Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 249 participants 121 participants 370 participants
3.48  (2.70) 3.48  (2.57) 3.48  (2.66)
[1]
Measure Description: 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.
Mini Mental State Exam (MMSE) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 249 participants 121 participants 370 participants
28.55  (1.83) 28.42  (1.72) 28.51  (1.79)
[1]
Measure Description: 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.
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 249 participants 121 participants 370 participants
29.25  (5.57) 28.46  (5.40) 29.00  (5.52)
[1]
Measure Description: 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.
1.Primary Outcome
Title Change From Baseline to 13 Weeks in Hamilton Depression Rating Scale (HAMD-17) Maier Subscale
Hide Description The Maier subscale (Items 1,2,7,8,9,10) represents symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe).
Time Frame baseline (Week 1), Week 13
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 95
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.34  (0.29) -3.90  (0.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments Tested was the null hypothesis that there would be no difference in changes from baseline (Week 1) to Week 13 on the HAMD-17 Maier subscale between duloxetine and placebo treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.397
Comments The a priori threshold for statistical significance was 0.05.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
2.Secondary Outcome
Title Change From Baseline on the 30-item Geriatric Depression Scale (GDS)
Hide Description 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).
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 200 90
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 13 change -6.01  (0.53) -4.53  (0.79)
Week 25 change -7.02  (0.58) -3.66  (1.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.115
Comments p-value is for difference between duloxetine and placebo on change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments p-value is for difference between duloxetine and placebo on change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
3.Secondary Outcome
Title Change From Baseline in the HAMD-17 Total Score, Subscales, and Individual Items
Hide Description Total Score assess depression severity (scores 0-52). Core, Maier and Bech subscales assess symptoms of depression (scores:0-20=Core; 0-24=Maier; 0-22=Bech). Anxiety/Somatization subscale assesses severity of anxiety (0-18). Retardation subscale assesses dysfunction in mood and work (0-14). Sleep subscale assesses insomnia (0-6). Individual item scores may range from 0-4 or 0-2. Higher numbers indicate more severe symptoms.
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized patients with non-missing data at baseline and post-baseline visit.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 95
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Total - Week 13 Change -7.42  (0.52) -7.15  (0.77)
Total - Week 25 Change -8.98  (0.57) -7.00  (1.01)
Maier subscale Week 25 Change -5.31  (0.29) -4.17  (0.54)
Bech subscale Week 13 Change -4.35  (0.30) -3.98  (0.46)
Bech subscale Week 25 Change -5.36  (0.31) -4.07  (0.58)
Core Mood subscale Week 13 Change -3.29  (0.24) -3.02  (0.36)
Core Mood subscale Week 25 Change -4.08  (0.23) -3.00  (0.43)
Anxiety/Somatization subscale Week 13 -2.38  (0.20) -2.26  (0.30)
Anxiety/Somatization subscale Week 25 -2.90  (0.22) -2.44  (0.38)
Sleep subscale Week 13 Change -1.14  (0.12) -1.14  (0.18)
Sleep subscale Week 25 Change -1.37  (0.13) -1.35  (0.24)
Retardation subscale Week 13 Change -2.70  (0.21) -2.73  (0.31)
Retardation subscale Week 25 Change -3.42  (0.20) -2.77  (0.38)
Item 1: Depressed Mood - Week 13 Change -1.13  (0.09) -1.02  (0.13)
Item 1: Depressed Mood Week 25 Change -1.36  (0.09) -1.02  (0.16)
Item 2: Feelings of Guilt Week 13 Change -0.70  (0.06) -0.60  (0.09)
Item 2: Feelings of Guilt Week 25 Change -0.91  (0.06) -0.65  (0.12)
Item 3: Suicide Week 13 Change -0.16  (0.04) -0.18  (0.05)
Item 3: Suicide Week 25 Change -0.19  (0.04) -0.11  (0.07)
Item 4: Insomnia Early Week 13 Change -0.37  (0.06) -0.29  (0.09)
Item 4: Insomnia Early Week 25 Change -0.42  (0.06) -0.41  (0.12)
Item 5: Insomnia Middle Week 13 Change -0.40  (0.06) -0.47  (0.09)
Item 5: Insomnia Middle Week 25 Change -0.49  (0.06) -0.46  (0.11)
Item 6: Insomnia Late Week 13 Change -0.36  (0.06) -0.41  (0.08)
Item 6: Insomnia Late Week 25 Change -0.45  (0.05) -0.53  (0.10)
Item 7: Work and Activities Week 13 Change -0.82  (0.08) -0.81  (0.12)
Item 7: Work and Activities Week 25 Change -1.12  (0.09) -0.87  (0.16)
Item 8: Retardation Week 13 Change -0.48  (0.05) -0.51  (0.08)
Item 8: Retardation Week 25 Change -0.57  (0.05) -0.54  (0.09)
Item 9: Agitation Week 13 Change -0.39  (0.06) -0.32  (0.08)
Item 9: Agitation Week 25 Change -0.45  (0.06) -0.53  (0.11)
Item 10: Anxiety/Psychic Week 13 Change -0.81  (0.07) -0.75  (0.11)
Item 10: Anxiety/Psychic Week 25 Change -0.98  (0.08) -0.85  (0.14)
Item 11: Anxiety (Somatic) Week 13 Change -0.49  (0.06) -0.55  (0.09)
Item 11: Anxiety (Somatic) Week 25 Change -0.70  (0.06) -0.60  (0.11)
Item 12: Somatic Symptom/Gastrointestinal Week 13 -0.16  (0.04) -0.20  (0.06)
Item 12: Somatic Symptom/Gastrointestinal Week 25 -0.23  (0.04) -0.26  (0.07)
Item 13: Somatic Symptoms/General Week 13 Change -0.41  (0.06) -0.40  (0.09)
Item 13: Somatic Symptoms/General Week 25 Change -0.52  (0.07) -0.59  (0.13)
Item 14: Genital Symptoms Week 13 Change -0.29  (0.06) -0.46  (0.08)
Item 14: Genital Symptoms Week 25 Change -0.41  (0.06) -0.47  (0.12)
Item 15: Hypochondriasis Week 13 Change -0.47  (0.06) -0.32  (0.08)
Item 15: Hypochondriasis Week 25 Change -0.49  (0.06) -0.39  (0.11)
Item 16: Loss of Weight Week 13 Change -0.02  (0.03) -0.09  (0.04)
Item 16: Loss of Weight Week 25 Change -0.13  (0.02) -0.01  (0.04)
Item 17: Insight Week 13 Change -0.09  (0.02) -0.10  (0.03)
Item 17: Insight Week 25 Change -0.07  (0.03) -0.11  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.773
Comments p-value is for HAMD-17 total score change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.084
Comments p-value is for HAMD-17 total score change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments p-value is for Maier subscale change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.488
Comments p-value is for Bech subscale change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments p-value is for HAMD-17 Bech subscale change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.529
Comments p-value is for Core Mood subscale change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments p-value is for Core Mood subscale change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.749
Comments p-value is for Anxiety/Somatization subscale change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.296
Comments p-value is for Anxiety/Somatization subscale change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.984
Comments p-value is for Sleep subscale change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.930
Comments p-value is for Sleep subscale change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.934
Comments p-value is for Retardation subscale change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.123
Comments p-value is for Retardation subscale change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
4.Secondary Outcome
Title Change From Baseline in the Brief Pain Inventory (BPI) Severity and Interference Scores
Hide Description The Brief Pain Inventory (severity and interference scales) (BPI) is a self-reported scale that measures the severity of pain and the interference of pain on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life.
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 191 87
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Worst Pain - Week 13 -0.66  (0.14) -0.18  (0.19)
Worst Pain - Week 25 -0.74  (0.14) -0.36  (0.20)
Least Pain - Week 13 -0.47  (0.11) -0.00  (0.15)
Least Pain - Week 25 -0.54  (0.11) -0.26  (0.16)
Average Pain - Week 13 -0.83  (0.13) -0.14  (0.18)
Average Pain - Week 25 -0.87  (0.12) -0.37  (0.18)
Pain Right Now - Week 13 -0.78  (0.13) -0.26  (0.18)
Pain Right Now - Week 25 -0.86  (0.13) -0.46  (0.18)
Interference with General Activity - Week13 -0.58  (0.13) -0.03  (0.19)
Interference with General Activity - Week 25 -0.65  (0.13) -0.23  (0.19)
Interference with Mood - Week 13 -0.82  (0.14) -0.03  (0.19)
Interference with Mood - Week 25 -0.95  (0.13) -0.25  (0.19)
Interference with Walking Ability - Week 13 -0.74  (0.14) -0.19  (0.20)
Interference with Walking Ability - Week 25 -0.75  (0.15) -0.24  (0.21)
Interference with Normal Work - Week 13 -0.72  (0.15) -0.01  (0.21)
Interference with Normal Work - Week 25 -0.79  (0.15) -0.19  (0.21)
Int. with Relations with other people- Week 13 -0.60  (0.13) -0.03  (0.19)
Int. with Relations with other people-Week 25 -0.73  (0.13) -0.18  (0.19)
Interference with Sleep - Week 13 -0.77  (0.15) -0.17  (0.21)
Interference with Sleep - Week 25 -0.94  (0.14) -0.26  (0.21)
Interference with Enjoyment of Life- Week 13 -0.93  (0.15) 0.03  (0.21)
Interference with Enjoyment of Life- Week 25 -1.04  (0.15) -0.08  (0.21)
Average Interference Score - Week 13 -0.76  (0.12) -0.07  (0.17)
Average Interference Score - Week 25 -0.86  (0.12) -0.19  (0.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments p-value is for Severity of Worst Pain Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.100
Comments p-value is for Severity of Worst Pain - Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments p-value is for Severity of Least Pain Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.126
Comments p-value is for Severity of Least Pain Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Severity of Average Pain Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments p-value is for Severity of Average Pain Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments p-value is for Severity of Pain Right Now Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments p-value is for Severity of Pain Right Now Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments p-value is for Interference with General Activity Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.060
Comments p-value is for Interference with General Activity Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Interference with Mood Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments p-value is for Interference with Mood Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments p-value is for Interference with Walking Ability Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments p-value is for Interference with Walking Ability Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments p-value is for Interference with Normal Work Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments p-value is for Interference with Normal Work Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments p-value is for Interference with Relations with Other People Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments p-value is for Interference with Relations with Other People Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments p-value is for Interference with Sleep Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments p-value is for Interference with Sleep Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Interference with Enjoyment of Life Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Interference with Enjoyment of Life Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Average Interference Score Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments p-value is for Average Interference Score Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
5.Secondary Outcome
Title Change From Baseline in the Numeric Rating Scales (NRS) for Pain Item Scores
Hide Description Numeric Rating Scales (Semantic Differential Scales) for Pain are 6 self-administered scales that assesses experience of overall pain, back pain, headache, shoulder pain, time in pain while awake, and pain interference with daily activities, during the past week. Each item is scored on a numeric 11-point semantic differential scale (0-10) from 0 = no pain to 10 = pain as severe as you can imagine; or 0 = none of the time to 10 = all of the time; or 0 = no interference to 10 = unable to do any activities at all.
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 191 87
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Overall Pain - Week 13 -0.65  (0.13) -0.05  (0.18)
Overall Pain - Week 25 -0.67  (0.13) -0.40  (0.19)
Headaches - Week 13 -0.32  (0.12) 0.01  (0.16)
Headaches - Week 25 -0.28  (0.12) 0.01  (0.18)
Back Pain - Week 13 -0.63  (0.14) 0.00  (0.20)
Back Pain - Week 25 -0.75  (0.14) -0.15  (0.21)
Shoulder Pain - Week 13 -0.54  (0.12) -0.22  (0.17)
Shoulder Pain - Week 25 -0.55  (0.13) -0.30  (0.18)
Pain Interference with Daily Activities - Week 13 -0.84  (0.14) -0.20  (0.20)
Pain Interference with Daily Activities - Week 25 -0.91  (0.15) -0.34  (0.21)
Time in Pain While Awake - Week 13 -0.75  (0.14) -0.04  (0.19)
Time in Pain While Awake - Week 25 -0.80  (0.13) -0.33  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .005
Comments p-value is for Overall Pain Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.204
Comments p-value is for Overall Pain Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments p-value is for Headaches Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.147
Comments p-value is for Headaches Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments p-value is for Back Pain Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments p-value is for Back Pain Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments p-value is for Shoulder Pain Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.231
Comments p-value is for Shoulder Pain Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments p-value is for Interference with Daily Activities Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments p-value is for Interference with Daily Activities Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments p-value is for Time in Pain While Awake Week 13 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments p-value is for Time in Pain While Awake Week 25 main effect of treatment.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
6.Secondary Outcome
Title Patient's Global Impression of Improvement (PGI-I) at 13 Weeks and 25 Weeks
Hide Description The PGI-Improvement scale is a patient-rated instrument that measures perceived improvement in symptoms. It is a 7-point scale where a score of 1 indicates that the patient is “very much improved,” a score of 4 indicates that the patient has experienced “no change,” and a score of 7 indicates that the patient is “very much worse.”
Time Frame Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 178 84
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 13 2.74  (0.13) 3.02  (0.19)
Week 25 2.38  (0.12) 2.85  (0.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.214
Comments p-value is for PGI-I at Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: PGI-I = Treatment + Pooled Investigator + Visit + Treatment* Visit
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .063
Comments p-value is for PGI-I at Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: PGI-I = Treatment + Pooled Investigator + Visit + Treatment* Visit
7.Secondary Outcome
Title Change From Baseline in the Clinical Global Impression-Severity (CGI-S)
Hide Description Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 203 94
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 13 Change -1.25  (0.09) -1.04  (0.13)
Week 25 Change -1.65  (0.09) -1.17  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .162
Comments p-value is for change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .009
Comments p-value is for change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change =Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
8.Secondary Outcome
Title Change From Baseline in the Mini-Mental State Exam (MMSE)
Hide Description Mini-Mental State Examination (MMSE)is a widely used rating measure of cognitive ability. Scores range from 0 to 30. The MMSE will be used to categorize patients as with or without dementia. Higher number indicates better cognitive ability. 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.
Time Frame baseline (Week 1), Week 9, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 159 69
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 9 Change (n=159, n=69) 0.12  (0.13) 0.24  (0.18)
Week 25 Change (n=161, n=71) 0.29  (0.13) 0.35  (0.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.555
Comments p-value is for change from baseline (Week 1) to Week 9.
Method ANCOVA
Comments Model: Change = Treatment + Pooled Investigator + Baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .785
Comments p-value is for change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change = Treatment + Pooled Investigator + Baseline
9.Secondary Outcome
Title Change From Baseline in the Quality of Life, Enjoyment, and Satisfaction Questionnaire (Q-LES-Q-SF)
Hide Description The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) measures the degree of enjoyment and satisfaction experienced in various areas of daily life. The short version is a self-administered 16 item scale evaluating satisfaction of general activities on a 5-point Likert scale that indicates the degree of enjoyment or satisfaction achieved during the past week (1 = very poor and 5 = very good).
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 167 82
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 13 Change 6.58  (0.71) 5.27  (0.98)
Week 25 Change (n=168, n=82) 7.44  (0.78) 4.79  (1.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.255
Comments p-value is for change from baseline (Week 1) to Week 13.
Method ANCOVA
Comments Model: Change = Treatment + Pooled Investigator + Baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments p-value is for change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change = Treatment + Pooled Investigator + Baseline
10.Secondary Outcome
Title Probability of Remission as Measured by the HAMD-17 Total Score ≤7 and ≤10
Hide Description Remission (visitwise binary outcome, yes/no) is defined as HAMD-17 Total Score ≤7 and ≤10. HAMD-17 measures depression severity. The total score can range from 0 (normal) to 52 (severe depression). The visitwise probability of patients meeting criteria for remission (either Total Score ≤7 or ≤10) was analyzed using a categorical, pseudo-likelihood-based repeated measures approach. This analysis included the fixed, categorical effects of treatment, investigator, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline score.
Time Frame Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 95
Least Squares Mean (Standard Error)
Unit of Measure: probability of remission
Remission (HAMD17 ≤ 7) - Week 13 0.37  (0.26) 0.33  (0.42)
Remission (HAMD17 ≤ 7) - Week 25 0.54  (0.22) 0.49  (0.46)
Remission (HAMD17 ≤ 10) - Week 13 0.54  (0.19) 0.53  (0.31)
Remission (HAMD17 ≤ 10) - Week 25 0.70  (0.21) 0.72  (0.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.706
Comments p-values for Week 13 remission (HAMD17 ≤ 7).
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Remission = Treatment + Pooled Investigator + Visit + Baseline + Treatment*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.694
Comments p-values for Week 25 Remission HAMD17 ≤ 7
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM)analysis model:Remission = Treatment + Pooled Investigator + Visit + Baseline + Treatment*Visit.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.864
Comments p-values for Week 13 Remission - HAMD17 ≤ 10
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM)analysis model:Remission = Treatment + Pooled Investigator + Visit + Baseline + Treatment*Visit.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.817
Comments p-values for Week 25 Remission - HAMD17 ≤ 10
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM)analysis model:Remission = Treatment + Pooled Investigator + Visit + Baseline + Treatment*Visit.
11.Secondary Outcome
Title Probability of Response at Endpoint as Measured by ≥50% Improvement in the HAMD-17 Total Score
Hide Description Response (visitwise binary outcome, yes/no) is defined as ≥ 50% reduction from baseline in the HAMD-17 total score. HAMD-17 measures depression severity. The total score can range from 0 (normal) to 52 (severe depression). The visitwise probability of patients meeting criteria for response was analyzed using a categorical, pseudo-likelihood-based repeated measures approach. This analysis included the fixed, categorical effects of treatment, investigator, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline score.
Time Frame Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 95
Least Squares Mean (Standard Error)
Unit of Measure: probability of response
Week 13 0.44  (0.19) 0.48  (0.29)
Week 25 0.61  (0.20) 0.72  (0.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.664
Comments p-value is for probability of response at Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM)analysis model:Response = Treatment + Pooled Investigator + Visit + Baseline + Treatment*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.310
Comments p-value is for probability of response at Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM)analysis model:Response = Treatment + Pooled Investigator + Visit + Baseline + Treatment*Visit.
12.Secondary Outcome
Title 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)
Hide Description Remission defined as HAMD-17 Total Score ≤7 and ≤10. HAMD-17 measures depression severity. Total score ranges: 0 (normal) to 52 (severe depression). Visitwise probability of patients achieving remission was analyzed using a categorical, pseudo-likelihood-based repeated measures approach. CIRS-G evaluates 14 organ-specific categories using a rating strategy of 0=no problems; 1=current mild problem/past significant problem; 2=moderate disability/morbidity; 3=severe/constant significant disability; and 4=extremely severe/immediate treatment required/end organ failure. Total score ranges: 0 to 56.
Time Frame Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized patients with non-missing data at baseline and post-baseline visit.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 95
Least Squares Mean (Standard Error)
Unit of Measure: probability of remission
Remission HAMD-17 ≤ 7 Week 13 (CIRS-G ≥ 6) 0.44  (0.07) 0.44  (0.10)
Remission HAMD-17 ≤ 7 Week 13 (CIRS-G < 6) 0.33  (0.07) 0.20  (0.10)
Remission HAMD-17 ≤ 10 Week 13 (CIRS-G ≥ 6) 0.53  (0.07) 0.52  (0.10)
Remission HAMD-17 ≤ 10 Week 13 (CIRS-G <6) 0.53  (0.07) 0.57  (0.14)
Remission HAMD-17 ≤ 7 Week 25 (CIRS-G ≥ 6) 0.52  (0.08) 0.42  (0.13)
Remission HAMD-17 ≤ 7 Week 25 (CIRS-G <6) 0.53  (0.08) 0.45  (0.25)
Remission HAMD-17 ≤ 10 Week 25 (CIRS-G ≥ 6) 0.71  (0.06) 0.65  (0.12)
Remission HAMD-17 ≤ 10 Week 25 (CIRS-G <6) 0.63  (0.08) 0.72  (0.25)
13.Secondary Outcome
Title Probability of Efficacy Onset as Measured by at Least 20% Sustained Reduction From Baseline in the HAMD-17 Maier Subscale at Week 3
Hide Description Patients are considered to have met onset (visitwise binary outcome, yes/no) criteria at a particular visit if they had at least 20% reduction from baseline in the HAMD-17 Maier subscale at that visit and at all subsequent visits in the acute phase. Maier subscale measures core symptoms of depression and scores range from 0 (normal) to 24 (severe). The visitwise probability of patients meeting onset criteria was analyzed using a categorical, pseudo-likelihood-based repeated measures approach.
Time Frame Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 201 95
Least Squares Mean (Standard Error)
Unit of Measure: Probability of onset
0.43  (0.04) 0.30  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM)analysis model: Onset = Treatment + Visit + Baseline + Treatment*Visit.
14.Secondary Outcome
Title Change From Baseline in Supine Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description [Not Specified]
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a baseline and at least one non-missing post-baseline value.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 246 118
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Systolic BP Week 13 Change 0.19  (0.94) -0.58  (1.39)
Diastolic BP Week 13 Change 1.89  (0.62) -1.58  (0.92)
Systolic BP Week 25 Change 2.22  (1.09) 0.54  (1.99)
Diastolic BP Week 25 Change 2.44  (0.68) 0.65  (1.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.637
Comments p-value is for Systolic BP change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments p-value is for Diastolic BP change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.452
Comments p-value is for Systolic BP change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.193
Comments p-value is for Diastolic BP change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
15.Secondary Outcome
Title Change From Baseline in Pulse Rate
Hide Description [Not Specified]
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a baseline and at least one non-missing post-baseline value.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 246 118
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute (bpm)
Week 13 Change 0.03  (0.60) -1.56  (0.88)
Week 25 Change 2.10  (0.69) -0.87  (1.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments p-value is for change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments p-value is for change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
16.Secondary Outcome
Title Change From Baseline in Weight
Hide Description [Not Specified]
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a baseline and at least one non-missing post-baseline value.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 248 121
Least Squares Mean (Standard Error)
Unit of Measure: kilograms (kg)
Week 13 Change -0.86  (0.17) 0.06  (0.26)
Week 25 Change -0.69  (0.22) -0.03  (0.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments p-value is for Weight change from baseline (Week 1) to Week 13.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.127
Comments p-value is for Weight change from baseline (Week 1) to Week 25.
Method Mixed Models Analysis
Comments Mixed Model Repeated Measures (MMRM) analysis model: Change = Treatment + Pooled Investigator + Visit + Treatment* Visit + Baseline + Baseline*Visit.
17.Secondary Outcome
Title Number of Participants With Abnormal Vital Signs and Weight at Any Time During the Study
Hide Description

A patient has a treatment-emergent elevated supine systolic blood pressure if the value is ≥140 with an increase ≥10 from baseline. A patient has a treatment-emergent elevated supine diastolic blood pressure if the value is ≥90 with an increase ≥10 from baseline. A patient has a treatment-emergent elevated supine pulse if the value is ≥100 with an increase ≥10 from baseline.

A patient has abnormal weight change if the gain or loss is ≥7% compared to baseline.

Time Frame Baseline (Week 1) through Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a normal baseline and at least one post-baseline value in each treatment group.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 248 121
Measure Type: Number
Unit of Measure: Participants
Diastolic Blood Pressure - High (n=210, n=98) 22 5
Pulse - High (n=243, n=115) 10 4
Systolic Blood Pressure - High (n=119, n=58) 28 7
Weight Change (gain) 11 2
Weight Change (loss) 15 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.135
Comments p-value is for Diastolic Blood Pressure.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments Pulse
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments p-value is for Pulse.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.107
Comments p-value is for Systolic Blood Pressure
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.235
Comments p-value is for Weight Change (gain)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.813
Comments p-value is for Weight Change (loss)
Method Fisher Exact
Comments [Not Specified]
18.Secondary Outcome
Title Number of Participants Experiencing Sustained Hypertension (SH) or Orthostatic Hypotension (OH)
Hide Description Sustained Hypertension is defined as supine systolic BP >= 140 (or diastolic BP >= 90) mm Hg and increase from baseline (highest value in baseline visit interval) >= 10 mm Hg for 3 or more consecutive visits in postbaseline visit interval. Orthostatic Hypotension is defined as standing diastolic BP at least 10 mm Hg less than the supine diastolic BP or the standing systolic BP at least 20 mm Hg less than the supine systolic BP at any time in postbaseline visit interval and a patient does not meet this criterion at any visit in baseline interval.
Time Frame baseline (Week 1) through Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a normal baseline and at least one post-baseline value in each treatment group.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 246 118
Measure Type: Number
Unit of Measure: Participants
Sustained Hypertension 5 1
Orthostatic Hypotension (n=183, n=90) 57 21
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.668
Comments p-value is for Sustained Hypertension
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.201
Comments p-value is for Orthostatic Hypotension
Method Fisher Exact
Comments [Not Specified]
19.Secondary Outcome
Title Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation
Hide Description Adverse Events and Serious Adverse Events leading to study discontinuation.
Time Frame baseline (Week 1) through Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients.
Arm/Group Title Duloxetine Placebo Non-rescue Placebo Rescue
Hide Arm/Group Description:
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.
Participants who were randomized to placebo at baseline and for whom treatment rescue was not required during continuation phase. 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 they continued to receive placebo until completing or discontinuing from the study.
Participants who were randomized to placebo at baseline and for whom rescue treatment was required during the continuation phase. 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 they were rescued to duloxetine 60 milligrams (mg) orally once daily (QD) beginning with duloxetine 30 mg QD orally for one week followed by duloxetine 60 mg QD orally until completing or discontinuing from the study.
Overall Number of Participants Analyzed 249 86 35
Measure Type: Number
Unit of Measure: participants
Total Discontinued due to Adverse Events 38 7 0
Diarrhoea 3 0 0
Fatigue 3 0 0
Headache 1 2 0
Nausea 3 0 0
Constipation 2 0 0
Dizziness 2 0 0
Hypertension 1 1 0
Memory impairment 2 0 0
Urinary Tract Infection 2 0 0
Vomiting 1 1 0
Alopecia 1 0 0
Anxiety 1 0 0
Blood pressure increased 0 1 0
Chills 1 0 0
Depression 1 0 0
Erectile dysfunction 1 0 0
Faecal incontinence 1 0 0
Gastrooesophageal reflux disease 1 0 0
Hip fracture 1 0 0
Insomnia 1 0 0
Intracranial aneurysm 1 0 0
Lethargy 1 0 0
Oesophageal adenocarcinoma metastatic 1 0 0
Palpitations 1 0 0
Paranasal sinus hypersecretion 1 0 0
Pneumoperitoneum 1 0 0
Presyncope 0 1 0
Rash pruritic 0 1 0
Renal failure acute 1 0 0
Suicidal ideation 1 0 0
Tremor 1 0 0
20.Secondary Outcome
Title Change From Baseline in Laboratory Values - Platelet Count
Hide Description Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a baseline and at least one post-baseline value in each treatment group.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 227 108
Mean (Standard Deviation)
Unit of Measure: billions per liter (bill/L)
Platelet Count Week 13 Change 7.92  (45.75) -4.66  (42.95)
Platelet Count Week 25 Change 10.58  (51.66) -6.11  (39.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments p-value is for Platelet Count change from baseline (Week 1) to Week 13.
Method ANOVA
Comments Model: Change=Treatment+Pooled Investigator
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Platelet Count change from baseline (Week 1) to Week 25.
Method ANOVA
Comments Model: Change=Treatment+Pooled Investigator
21.Secondary Outcome
Title Change From Baseline in Laboratory Values - Uric Acid
Hide Description Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
Time Frame baseline (Week 1), Week 13, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a baseline and at least one post-baseline value in each treatment group.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 230 112
Mean (Standard Deviation)
Unit of Measure: micromole/liter
Week 13 Change -11.63  (63.05) 9.30  (47.39)
Week 25 Change -9.93  (59.64) 10.26  (48.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Uric Acid change from baseline (Week 1) to Week 13.
Method ANOVA
Comments Model: Change = Treatment + Pooled Investigator
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is for Uric Acid change from baseline (Week 1) to Week 25.
Method ANOVA
Comments Model: Change = Treatment + Pooled Investigator
22.Secondary Outcome
Title Change From Baseline in Laboratory Values - Erythrocyte Count
Hide Description Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
Time Frame baseline (Week 1), Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a baseline and at least one post-baseline value in each treatment group.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 228 109
Mean (Standard Deviation)
Unit of Measure: Trillion/Liter
Erythrocyte Count -0.04  (0.29) 0.01  (0.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments p-value is for Erythrocyte Count change from baseline (Week 1) to Week 25.
Method ANOVA
Comments Model: Change=Treatment+Pooled Investigator
23.Secondary Outcome
Title Change From Baseline in Laboratory Values - Hemoglobin, Mean Cell Hemoglobin Concentration (MCHC)
Hide Description Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
Time Frame baseline (Week 1), Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a baseline and at least one post-baseline value in each treatment group.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 228 109
Mean (Standard Deviation)
Unit of Measure: Micromole/liter (Fe)
Hemoglobin Week 25 Change -0.11  (0.56) 0.01  (0.46)
Mean Cell Hemoglobin Concentration Week 25 Change -0.20  (0.81) -0.02  (0.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments p-value is for Hemoglobin change from baseline (Week 1) to Week 25.
Method ANOVA
Comments Model: Change = Treatment + Pooled Investigator
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments p-value is for Mean Cell Hemoglobin Concentration change from baseline (Week 1) to Week 25.
Method ANOVA
Comments Model: Change=Treatment+Pooled Investigator
24.Secondary Outcome
Title Change From Baseline in Laboratory Values - Chloride and Fasting Glucose
Hide Description Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
Time Frame baseline (Week 1), Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a baseline and at least one post-baseline value in each treatment group.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 230 112
Mean (Standard Deviation)
Unit of Measure: millimole/liter
Chloride Week 25 Change -0.63  (2.83) 0.01  (2.77)
Fasting Glucose Week 25 Change (n=155, n=67) 0.37  (1.88) -0.11  (1.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments p-value is for Chloride change from baseline (Week 1) to Week 25.
Method ANOVA
Comments Model: Change = Treatment + Pooled Investigator
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments p-value is for Fasting Glucose change from baseline (Week 1) to Week 25.
Method ANOVA
Comments Model: Change=Treatment+Pooled Investigator
25.Secondary Outcome
Title Number of Participants With Abnormal Laboratory Values - Low Leukocyte Count
Hide Description The number of participants with abnormal laboratory values at any time during the study period. Results are reported for laboratory analytes that exhibited statistically significantly different proportions of participants who had abnormal values between treatment groups. Statistical significance was considered at the 0.05 level. The lower limit of normal for leukocyte count is 3.8 Billion/Liter. Participants who had a value below that number were considered to have abnormally low leukocyte count.
Time Frame baseline (Week 1) through Week 13
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with a normal baseline and at least one post-baseline value in each treatment group.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 225 109
Measure Type: Number
Unit of Measure: participants
Leukocyte Count (Low) 11 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
26.Secondary Outcome
Title Change From Baseline in Electrocardiograms
Hide Description The Electrocardiogram measures include the following time intervals: QT interval, QT Interval Corrected for Heart Rate Using Fridericia’s Formula (QTcF), QT Interval Corrected for Heart Rate Using Bazett's Formula (QTcB), PR interval and QRS interval.
Time Frame baseline (Week 1), Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a baseline and at least one non-missing post baseline value.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 194 68
Least Squares Mean (Standard Error)
Unit of Measure: millisecond (msec)
QT Interval Week 25 Change -11.80  (2.19) -10.95  (3.43)
QTcF Interval Week 25 Change -5.02  (1.48) -5.91  (2.33)
QTcB Interval Week 25 Change -1.38  (1.61) -3.78  (2.55)
PR Interval Week 25 Change -5.91  (1.45) -1.34  (2.32)
QRS Interval Week 25 Change -1.11  (0.80) -3.25  (1.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.815
Comments p-value is for QT Interval change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.721
Comments p-value is for QTcF Interval change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.376
Comments p-value is for QTcB Interval change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments p-value is for PR Interval change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.110
Comments p-value is for QRS Interval change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
27.Secondary Outcome
Title Number of Participants With Successful Treatment Outcome
Hide Description Successful treatment outcome defined as: Participant completed the study and being in remission (HAMD-17 Total score ≤7 and ≤10) at least for the last two visits (4 weeks)of the study. The HAMD-17 is used to assess the severity of depression. The total score ranges from 0 (not at all depressed) to 52 (severely depressed).
Time Frame Baseline (Week 1) through Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and that have non-missing successful treatment values.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 204 95
Measure Type: Number
Unit of Measure: participants
Successful Treatment Outcome (with HAMD17 ≤ 7) 55 17
Successful Treatment Outcome (with HAMD17 ≤ 10) 74 21
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.110
Comments p-value is for Successful Treatment Outcome defined with HAMD-17 ≤7 criteria.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments p-value is for Successful Treatment Outcome defined with HAMD-17 ≤10 criteria.
Method Fisher Exact
Comments [Not Specified]
28.Secondary Outcome
Title 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
Hide Description The cognitive assessment battery is composed of four tests: Verbal Learning (score 0-15)and Delayed Recall(score 0-15) test, SDST(Score 0-133),2DCT(score 0-40),Trail Making(Part B)(score 0-180).They are designed to challenge the patient's abilities in the following areas: verbal learning and memory; attention to visually presented material; and working memory and executive function. Composite Cognitive score(0-51)is derived from normalized individual test scores. For Trail Making Test,lower number indicates better cognition. For all other test scores,higher number indicates better cognition.
Time Frame baseline (Week 1), Week 9, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
All participants randomized under protocol amendment c,d,e, and have a baseline observation and at least one post-randomization observation.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 183 90
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Composite Cognitive Score Week 9 -0.38  (0.38) 0.01  (0.51)
Composite Cognitive Score Week 25 0.96  (0.40) 0.31  (0.54)
Learning Trials Score Week 9 -0.06  (0.12) -0.04  (0.17)
Learning Trials Score Week 25 0.34  (0.13) 0.06  (0.18)
Delayed Recall Score Week 9 -0.65  (0.21) -0.59  (0.28)
Delayed Recall Score Week 25 0.12  (0.22) -0.36  (0.29)
SDST Score Week 9 1.98  (0.76) 3.99  (1.04)
SDST Score Week 25 5.60  (0.84) 3.61  (1.15)
2DCT Score Week 9 0.30  (0.46) 0.94  (0.63)
2DCT Score Week 25 0.87  (0.51) 1.01  (0.70)
Trail Making Test (Part B) Week 9 -5.60  (2.90) -3.09  (4.00)
Trail Making Test (Part B) Week 25 -1.59  (2.82) -6.86  (3.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.511
Comments p-value is for Composite Cognitive Score change from baseline (Week 1) to Week 9.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.300
Comments p-value is for Composite Cognitive Score change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.922
Comments p-value is for Learning Trials Score change from baseline (Week 1) to Week 9.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.190
Comments p-value is for Learning Trials Score change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.850
Comments p-value is for Delayed Recall Score change from baseline (Week 1) to Week 9.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.158
Comments p-value is for Delayed Recall Score change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.099
Comments p-value is for SDST Score change from baseline (Week 1) to Week 9.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.141
Comments p-value is for SDST Score change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.379
Comments p-value is for 2DCT Score change from baseline (Week 1) to Week 9.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.858
Comments p-value is for 2DCT Score change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.591
Comments p-value is for Trail Making Test Score change from baseline (Week 1) to Week 9.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.242
Comments p-value is for Trail Making Test Score change from baseline (Week 1) to Week 25.
Method ANCOVA
Comments Model: Change=Treatment+Pooled Investigator+Baseline
Time Frame Baseline (Week 1) through Week 25.
Adverse Event Reporting Description The event of fall was collected using a solicited Falls Assessment questionnaire at each visit.
 
Arm/Group Title Duloxetine Placebo Rescued Placebo
Hide Arm/Group Description 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. 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. Results are for the randomized placebo patients who reported events while they were on 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 were rescued to duloxetine 60 milligrams (mg) orally once daily (QD) beginning with duloxetine 30 mg QD orally for one week followed by duloxetine 60 mg QD orally for the remainder of the study. Results are for the randomized placebo patients who were rescued to duloxetine and reported events while they were on duloxetine.
All-Cause Mortality
Duloxetine Placebo Rescued Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Duloxetine Placebo Rescued Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/249 (5.22%)      4/121 (3.31%)      1/35 (2.86%)    
Cardiac disorders       
Arrhythmia  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Atrial flutter  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Coronary artery occlusion  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Gastrointestinal disorders       
Pneumoperitoneum  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
General disorders       
Chest pain  1  2/249 (0.80%)  2 0/121 (0.00%)  0 0/35 (0.00%)  0
Infections and infestations       
Abscess intestinal  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Influenza  1  0/249 (0.00%)  0 1/121 (0.83%)  1 0/35 (0.00%)  0
Injury, poisoning and procedural complications       
Ankle fracture  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Head injury  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Hip fracture  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Metabolism and nutrition disorders       
Diabetes mellitus  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Spinal osteoarthritis  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Oesophageal adenocarcinoma metastatic  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Nervous system disorders       
Intracranial aneurysm  1  1/249 (0.40%)  1 0/121 (0.00%)  0 0/35 (0.00%)  0
Presyncope  1  0/249 (0.00%)  0 1/121 (0.83%)  1 0/35 (0.00%)  0
Renal and urinary disorders       
Renal failure acute  1  1/249 (0.40%)  1