Trial Outcomes & Findings for A Duloxetine Dosing Strategy Study in Korean Patients With Major Depressive Disorder (NCT NCT00960986)
NCT ID: NCT00960986
Last Updated: 2014-12-31
Results Overview
AMDP-5 AE scale Item 112 (nausea) measured nausea severity during treatment (Week 0-8). The scores ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe.
COMPLETED
PHASE4
249 participants
1 week and 8 weeks
2014-12-31
Participant Flow
Period 1 was a 3- to 30-day screening and washout period; Period 2 (Week 0-1) was a 1-week initial dosing period (randomization to duloxetine 30 mg with food, 30 mg without food, 60 mg with food, or 60 mg without food); Period 3 (Week 1-8) was a 7-week therapy period (treatment switched to duloxetine 60 mg once daily (QD) until study end.
Participant milestones
| Measure |
Duloxetine 60 mg With Food
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Period 1 (Screening and Washout)
STARTED
|
59
|
63
|
63
|
64
|
|
Period 1 (Screening and Washout)
COMPLETED
|
56
|
59
|
59
|
61
|
|
Period 1 (Screening and Washout)
NOT COMPLETED
|
3
|
4
|
4
|
3
|
|
Period 2 (1-week Initial Dosing Period)
STARTED
|
56
|
59
|
59
|
61
|
|
Period 2 (1-week Initial Dosing Period)
COMPLETED
|
56
|
59
|
59
|
61
|
|
Period 2 (1-week Initial Dosing Period)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3 (7-week Therapy Period)
STARTED
|
56
|
59
|
59
|
61
|
|
Period 3 (7-week Therapy Period)
COMPLETED
|
26
|
36
|
39
|
36
|
|
Period 3 (7-week Therapy Period)
NOT COMPLETED
|
30
|
23
|
20
|
25
|
Reasons for withdrawal
| Measure |
Duloxetine 60 mg With Food
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Period 1 (Screening and Washout)
Adverse Event
|
1
|
2
|
1
|
1
|
|
Period 1 (Screening and Washout)
Lost to Follow-up
|
0
|
0
|
2
|
1
|
|
Period 1 (Screening and Washout)
Protocol Violation
|
1
|
0
|
0
|
0
|
|
Period 1 (Screening and Washout)
Withdrawal by Subject
|
1
|
2
|
1
|
1
|
|
Period 3 (7-week Therapy Period)
Adverse Event
|
17
|
15
|
10
|
12
|
|
Period 3 (7-week Therapy Period)
Death
|
0
|
0
|
1
|
0
|
|
Period 3 (7-week Therapy Period)
Lost to Follow-up
|
0
|
0
|
1
|
0
|
|
Period 3 (7-week Therapy Period)
Protocol Violation
|
10
|
4
|
3
|
11
|
|
Period 3 (7-week Therapy Period)
Withdrawal by Subject
|
2
|
2
|
4
|
2
|
|
Period 3 (7-week Therapy Period)
Lack of Efficacy
|
1
|
2
|
1
|
0
|
Baseline Characteristics
A Duloxetine Dosing Strategy Study in Korean Patients With Major Depressive Disorder
Baseline characteristics by cohort
| Measure |
Duloxetine 60 mg With Food
n=59 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=63 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=63 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=64 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
Total
n=249 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
44.65 years
n=5 Participants
|
47.90 years
n=7 Participants
|
49.94 years
n=5 Participants
|
44.65 years
n=4 Participants
|
46.81 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
43 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
177 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
72 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Korean
|
59 participants
n=5 Participants
|
63 participants
n=7 Participants
|
63 participants
n=5 Participants
|
64 participants
n=4 Participants
|
249 participants
n=21 Participants
|
|
Region of Enrollment
Korea, Republic of
|
59 participants
n=5 Participants
|
63 participants
n=7 Participants
|
63 participants
n=5 Participants
|
64 participants
n=4 Participants
|
249 participants
n=21 Participants
|
|
Body Mass Index (BMI)
|
24.56 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 4.034 • n=5 Participants
|
23.28 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 3.133 • n=7 Participants
|
23.06 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 3.430 • n=5 Participants
|
23.84 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 3.612 • n=4 Participants
|
23.67 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 3.584 • n=21 Participants
|
|
Previously diagnosed with major depressive disorder (MDD)
|
59 participants
n=5 Participants
|
63 participants
n=7 Participants
|
63 participants
n=5 Participants
|
64 participants
n=4 Participants
|
249 participants
n=21 Participants
|
|
Duration since first major depressive disorder (MDD) episode
|
1.47 years
n=5 Participants
|
2.65 years
n=7 Participants
|
2.52 years
n=5 Participants
|
1.29 years
n=4 Participants
|
1.92 years
n=21 Participants
|
|
Age at first major depressive disorder (MDD) episode
|
41.21 years
n=5 Participants
|
43.33 years
n=7 Participants
|
43.86 years
n=5 Participants
|
41.58 years
n=4 Participants
|
42.52 years
n=21 Participants
|
|
Number of previous MDD episodes/exacerbations in the last 24 months
|
1.0 number of episodes in last 24 months
n=5 Participants
|
1.0 number of episodes in last 24 months
n=7 Participants
|
1.0 number of episodes in last 24 months
n=5 Participants
|
1.0 number of episodes in last 24 months
n=4 Participants
|
1.0 number of episodes in last 24 months
n=21 Participants
|
|
Received previous therapy for current episode
yes
|
18 participants
n=5 Participants
|
25 participants
n=7 Participants
|
18 participants
n=5 Participants
|
26 participants
n=4 Participants
|
87 participants
n=21 Participants
|
|
Received previous therapy for current episode
no
|
41 participants
n=5 Participants
|
38 participants
n=7 Participants
|
45 participants
n=5 Participants
|
38 participants
n=4 Participants
|
162 participants
n=21 Participants
|
|
17-item Hamilton Depression Rating Scale (HAMD-17) Total Score
|
21.0 units on a scale
STANDARD_DEVIATION 5.18 • n=5 Participants
|
22.3 units on a scale
STANDARD_DEVIATION 5.69 • n=7 Participants
|
22.9 units on a scale
STANDARD_DEVIATION 5.45 • n=5 Participants
|
20.3 units on a scale
STANDARD_DEVIATION 5.23 • n=4 Participants
|
21.6 units on a scale
STANDARD_DEVIATION 5.46 • n=21 Participants
|
|
Clinical Global Impression of Severity (CGI-S) Score
|
4.4 units on a scale
n=5 Participants
|
4.5 units on a scale
n=7 Participants
|
4.7 units on a scale
n=5 Participants
|
4.2 units on a scale
n=4 Participants
|
4.4 units on a scale
n=21 Participants
|
|
Association for Methodology and Documentation in Psychiatry (AMDP-5) Item 112 (Nausea) Score
|
0.3 units on a scale
STANDARD_DEVIATION 0.72 • n=5 Participants
|
0.2 units on a scale
STANDARD_DEVIATION 0.59 • n=7 Participants
|
0.2 units on a scale
STANDARD_DEVIATION 0.61 • n=5 Participants
|
0.1 units on a scale
STANDARD_DEVIATION 0.38 • n=4 Participants
|
0.2 units on a scale
STANDARD_DEVIATION 0.58 • n=21 Participants
|
PRIMARY outcome
Timeframe: 1 week and 8 weeksPopulation: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
AMDP-5 AE scale Item 112 (nausea) measured nausea severity during treatment (Week 0-8). The scores ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea)
Week 0-1
|
1.4 units on a scale
Interval 1.06 to 1.69
|
1.2 units on a scale
Interval 0.89 to 1.49
|
0.9 units on a scale
Interval 0.62 to 1.11
|
0.8 units on a scale
Interval 0.57 to 1.06
|
|
Mean Maximum Nausea Severity, Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea)
Week 1-8 (n=35; n=43; n=48; n=46)
|
0.5 units on a scale
Interval 0.25 to 0.67
|
0.5 units on a scale
Interval 0.27 to 0.66
|
0.7 units on a scale
Interval 0.45 to 0.96
|
0.4 units on a scale
Interval 0.19 to 0.59
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken. N = number of subjects with a baseline and post-baseline result at the Week 8 visit.
Scores for AE scale Item 112 (nausea) of AMDP-5 (Week 0-8) ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe. Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=28 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=37 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=39 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=37 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 8-Week Endpoint in Association for Methodology and Documentation in Psychiatry (AMDP-5) Adverse Event (AE) Scale Item 112 (Nausea)
|
-0.02 units on a scale
Standard Error 0.08
|
-0.02 units on a scale
Standard Error 0.07
|
-0.01 units on a scale
Standard Error 0.07
|
-1.12 units on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Baseline, 1 week and 8 weeksPopulation: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
Gastric events scores (average of Item 112 \[nausea\] + Item 113 \[vomiting\]) of AMDP-5 (Week 0-8) ranged from 0-3: 0=Not present; 1=Mild; 2=Moderate; 3=Severe. Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score
1-week change
|
0.73 units on a scale
Standard Error 0.10
|
0.72 units on a scale
Standard Error 0.10
|
0.35 units on a scale
Standard Error 0.10
|
0.37 units on a scale
Standard Error 0.10
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Gastric Events Score
8-week change (n=28; n=37; n=39; n=37)
|
-0.04 units on a scale
Standard Error 0.04
|
-0.04 units on a scale
Standard Error 0.04
|
-0.04 units on a scale
Standard Error 0.04
|
-0.09 units on a scale
Standard Error 0.04
|
SECONDARY outcome
Timeframe: Baseline, 1 week, 8 weeksPopulation: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
AMDP-5 common AEs score was used to create a composite measure of AEs from previous duloxetine studies (incidence \>5% and 2X placebo rate). The common AEs total score was the sum of the following 8 AMDP-5 items: 1) Mean of Item 112 (nausea) + 113 (vomiting); 2) Item 111 (dry mouth); 3) Item 115 (constipation); 4) Mean of Items 101-104 (insomnia); Item 122 (increased perspiration); 8) Item 106 (decreased appetite). Score was based on a 5-point scale: 1=absent, 2=mild, 3=moderate, 4=severe, 5=extremely severe; Higher score=worse severity.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score
1-week change
|
1.25 units on a scale
Standard Error 0.44
|
1.28 units on a scale
Standard Error 0.42
|
-0.00 units on a scale
Standard Error 0.43
|
-0.37 units on a scale
Standard Error 0.41
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Association for Methodology and Documentation in Psychiatry (AMDP-5) Measure: Common Adverse Events (AEs) Score
8-week change (n=28; n=37; n=39; n=37)
|
-3.54 units on a scale
Standard Error 0.47
|
-2.99 units on a scale
Standard Error 0.42
|
-2.33 units on a scale
Standard Error 0.41
|
-3.23 units on a scale
Standard Error 0.41
|
SECONDARY outcome
Timeframe: Baseline, 1 week, 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
The HAMD-17 total score ranged from 0 (not at all depressed)-52 (severely depressed). Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariance matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score
1-week change
|
-2.83 units on a scale
Standard Error 0.57
|
-2.85 units on a scale
Standard Error 0.55
|
-3.84 units on a scale
Standard Error 0.56
|
-4.34 units on a scale
Standard Error 0.54
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score
8-week change (n=28; n=37; n=39; n=37)
|
-15.39 units on a scale
Standard Error 1.01
|
-13.45 units on a scale
Standard Error 0.90
|
-13.60 units on a scale
Standard Error 0.88
|
-13.07 units on a scale
Standard Error 0.89
|
SECONDARY outcome
Timeframe: Baseline, 1 week, 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
The HAMD-17 Maier subscale (Items 1, 2, 7, 8, 9, 10 of HAMD-17 questionnaire) represented the "core" symptoms of depression. Total subscale scores ranged from 0 (normal)-24 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale
1-week change
|
-2.06 units on a scale
Standard Error 0.33
|
-1.90 units on a scale
Standard Error 0.32
|
-2.15 units on a scale
Standard Error 0.32
|
-2.64 units on a scale
Standard Error 0.31
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale
8-week change (n=28; n=37; n=39; n=37)
|
-8.01 units on a scale
Standard Error 0.50
|
-7.12 units on a scale
Standard Error 0.45
|
-7.55 units on a scale
Standard Error 0.44
|
-7.30 units on a scale
Standard Error 0.44
|
SECONDARY outcome
Timeframe: Baseline, 1 week, 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
The HAMD-17 Core Mood subscale (Items 1, 2, 3, 7, 8 of HAMD-17 questionnaire) represented the core symptoms of depression. Total subscale scores ranged from 0 (normal)-20 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale
1-week change
|
-1.43 units on a scale
Standard Error 0.27
|
-1.18 units on a scale
Standard Error 0.26
|
-1.52 units on a scale
Standard Error 0.26
|
-1.76 units on a scale
Standard Error 0.25
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Mood Subscale
8-week change (n=28; n=37; n=39; n=37)
|
-6.18 units on a scale
Standard Error 0.40
|
-5.39 units on a scale
Standard Error 0.36
|
-5.85 units on a scale
Standard Error 0.35
|
-5.67 units on a scale
Standard Error 0.35
|
SECONDARY outcome
Timeframe: Baseline, 1 week, 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
The HAMD-17 Anxiety/Somatization subscale (Items 10, 11, 12, 13, 15, 17 of HAMD-17 questionnaire) evaluated the severity of psychic and somatic manifestations of anxiety and agitation. Total subscale scores ranged from 0 (normal)-18 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale
1-week change
|
-0.75 units on a scale
Standard Error 0.25
|
-1.15 units on a scale
Standard Error 0.24
|
-1.36 units on a scale
Standard Error 0.24
|
-1.41 units on a scale
Standard Error 0.23
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Subscale
8-week change (n=28; n=37; n=39; n=37)
|
-4.93 units on a scale
Standard Error 0.41
|
-4.50 units on a scale
Standard Error 0.36
|
-4.57 units on a scale
Standard Error 0.35
|
-4.26 units on a scale
Standard Error 0.35
|
SECONDARY outcome
Timeframe: Baseline, 1 week, 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
The HAMD-17 Retardation/Somatization subscale (Items 1, 7, 8, 14 of HAMD-17 questionnaire) evaluated dysfunction in mood, work, sexual activity, and overall motor retardation. Total subscale scores ranged from 0 (normal)-14 (severe). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale
1-week change
|
-0.83 units on a scale
Standard Error 0.22
|
-0.87 units on a scale
Standard Error 0.21
|
-1.02 units on a scale
Standard Error 0.22
|
-1.20 units on a scale
Standard Error 0.21
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation/Somatization Subscale
8-week change (n=28; n=37; n=39; n=37)
|
-4.92 units on a scale
Standard Error 0.35
|
-4.37 units on a scale
Standard Error 0.31
|
-4.63 units on a scale
Standard Error 0.31
|
-4.55 units on a scale
Standard Error 0.31
|
SECONDARY outcome
Timeframe: Baseline, 1 week, 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
The HAMD-17 Sleep subscale (Items 4, 5, 6 of HAMD-17 questionnaire) evaluated initial, middle, and late insomnia. Total subscale scores ranged from 0 (no difficulty)-6 (difficulty). Least Squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariate matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale
1-week change
|
-0.72 units on a scale
Standard Error 0.21
|
-0.64 units on a scale
Standard Error 0.21
|
-0.66 units on a scale
Standard Error 0.21
|
-1.01 units on a scale
Standard Error 0.20
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Subscale
8-week change (n=28; n=37; n=39; n=37)
|
-2.77 units on a scale
Standard Error 0.27
|
-2.32 units on a scale
Standard Error 0.24
|
-2.09 units on a scale
Standard Error 0.23
|
-2.10 units on a scale
Standard Error 0.23
|
SECONDARY outcome
Timeframe: Baseline, 1 week, 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
The CGI-S Rating Scale was a 7-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; or 7=extremely ill. Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction, and an unstructured covariance matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S)
1-week change
|
-0.36 units on a scale
Standard Error 0.09
|
-0.36 units on a scale
Standard Error 0.09
|
-0.44 units on a scale
Standard Error 0.09
|
-0.63 units on a scale
Standard Error 0.09
|
|
Mean Change From Baseline to 1-Week and 8-Week Endpoints in Clinical Global Impressions of Severity (CGI-S)
8-week change (n=28; n=37; n=39; n=37)
|
-2.43 units on a scale
Standard Error 0.17
|
-2.13 units on a scale
Standard Error 0.15
|
-2.23 units on a scale
Standard Error 0.15
|
-2.27 units on a scale
Standard Error 0.15
|
SECONDARY outcome
Timeframe: 1 week, 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
The PGI-I Rating Scale was a 7-point scale: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Least squares (LS) Means were adjusted for treatment group, site, visit and treatment-by-visit interaction, gender, age, baseline score and baseline score-by-visit interaction and an unstructured covariance matrix.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks
1-week change
|
3.72 units on a scale
Standard Error 0.13
|
3.77 units on a scale
Standard Error 0.13
|
3.52 units on a scale
Standard Error 0.13
|
3.47 units on a scale
Standard Error 0.12
|
|
Patient Global Impression of Improvement (PGI-I) at 1 Week and 8 Weeks
8-week change (n=28; n=37; n=39; n=37)
|
2.31 units on a scale
Standard Error 0.19
|
2.40 units on a scale
Standard Error 0.17
|
2.36 units on a scale
Standard Error 0.16
|
2.40 units on a scale
Standard Error 0.16
|
SECONDARY outcome
Timeframe: Baseline to onset of nausea (Baseline up to 8 weeks)Population: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
Events of nausea were taken from the adverse event (AE) data. Participants were censored based on the following rules: 1=study discontinuation date if the participant discontinues the study; 2=study lost to follow-up date if the participant drops out of the study.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=40 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=38 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=38 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=37 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Time to Onset of Nausea
|
2.0 days
Interval 1.0 to 9.0
|
1.0 days
Interval 1.0 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
7.0 days
Interval 2.0 to 56.0
|
6.0 days
Interval 1.0 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
SECONDARY outcome
Timeframe: Nausea onset up to nausea resolve (Baseline up to 8 weeks)Population: The safety population included all participants who took at least 1 study drug dose analysed according to the drug dose actually taken.
Events of nausea were taken from the adverse event (AE) data. Participants were censored based on the following rules: 1=study discontinuation date if the participant discontinues the study; 2=study lost to follow-up date if the participant drops out of the study.
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=33 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=25 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=27 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=30 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Time to Resolve Nausea
|
6.0 days
Interval 4.0 to 9.0
|
8.0 days
Interval 5.0 to 15.0
|
15.0 days
Interval 9.0 to 22.0
|
6.0 days
Interval 4.0 to 7.0
|
SECONDARY outcome
Timeframe: Baseline up to 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
Response was defined as ≥50% decrease from baseline on the 17-item Hamilton Depression Rating Scale (HAMD-17) total score. HAMD-17 total scores ranged from 0 (not at all depressed)-52 (severely depressed).
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Percentage of Participants Achieving Response
|
51.8 percentage of participants
|
49.2 percentage of participants
|
47.5 percentage of participants
|
47.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to 8 weeksPopulation: The efficacy population included the number of participants with baseline and at least 1 post-baseline value analysed under the intent-to-treat (ITT) principle according to the drug dose they were assigned.
Remission was defined as 17-item Hamilton Depression Rating Scale (HAMD-17) total score ≤7. HAMD-17 total scores ranged from 0 (not at all depressed)-52 (severely depressed).
Outcome measures
| Measure |
Duloxetine 60 mg With Food
n=56 Participants
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 60 mg Without Food
n=59 Participants
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
Duloxetine 30 mg With Food
n=59 Participants
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 30 mg Without Food
n=61 Participants
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
|---|---|---|---|---|
|
Percentage of Patients Achieving Remission
|
42.9 percentage of participants
|
37.3 percentage of participants
|
35.6 percentage of participants
|
32.8 percentage of participants
|
Adverse Events
Duloxetine 30 mg With Food
Duloxetine 60 mg With Food
Duloxetine 30 mg Without Food
Duloxetine 60 mg Without Food
Serious adverse events
| Measure |
Duloxetine 30 mg With Food
n=63 participants at risk
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 60 mg With Food
n=59 participants at risk
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 30 mg Without Food
n=64 participants at risk
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
Duloxetine 60 mg Without Food
n=63 participants at risk
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/63
|
1.7%
1/59 • Number of events 1
|
0.00%
0/64
|
0.00%
0/63
|
|
Infections and infestations
Pelvic inflammatory disease
|
0.00%
0/63
|
1.7%
1/59 • Number of events 1
|
0.00%
0/64
|
0.00%
0/63
|
|
Injury, poisoning and procedural complications
Muscle injury
|
0.00%
0/63
|
0.00%
0/59
|
1.6%
1/64 • Number of events 1
|
0.00%
0/63
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/63
|
0.00%
0/59
|
1.6%
1/64 • Number of events 1
|
0.00%
0/63
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
|
0.00%
0/63
|
0.00%
0/59
|
1.6%
1/64 • Number of events 1
|
0.00%
0/63
|
|
Psychiatric disorders
Completed suicide
|
1.6%
1/63 • Number of events 1
|
0.00%
0/59
|
0.00%
0/64
|
0.00%
0/63
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.00%
0/63
|
1.7%
1/59 • Number of events 1
|
0.00%
0/64
|
0.00%
0/63
|
Other adverse events
| Measure |
Duloxetine 30 mg With Food
n=63 participants at risk
Duloxetine 30 mg capsule po QD with food for 1 week, then 60 mg with food for 7 weeks
|
Duloxetine 60 mg With Food
n=59 participants at risk
Duloxetine 60 milligram (mg) capsule oral (po), once daily (QD) with food for 8 weeks
|
Duloxetine 30 mg Without Food
n=64 participants at risk
Duloxetine 30 mg capsule po QD without food for 1 week, then 60 mg without food for 7 weeks
|
Duloxetine 60 mg Without Food
n=63 participants at risk
Duloxetine 60 mg capsule po QD without food for 8 weeks
|
|---|---|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/63
|
6.8%
4/59 • Number of events 4
|
3.1%
2/64 • Number of events 2
|
4.8%
3/63 • Number of events 3
|
|
Eye disorders
Vision blurred
|
7.9%
5/63 • Number of events 5
|
1.7%
1/59 • Number of events 1
|
0.00%
0/64
|
3.2%
2/63 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal discomfort
|
4.8%
3/63 • Number of events 3
|
10.2%
6/59 • Number of events 6
|
10.9%
7/64 • Number of events 7
|
6.3%
4/63 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
19.0%
12/63 • Number of events 12
|
15.3%
9/59 • Number of events 10
|
14.1%
9/64 • Number of events 10
|
15.9%
10/63 • Number of events 11
|
|
Gastrointestinal disorders
Diarrhoea
|
6.3%
4/63 • Number of events 4
|
5.1%
3/59 • Number of events 3
|
6.2%
4/64 • Number of events 5
|
4.8%
3/63 • Number of events 4
|
|
Gastrointestinal disorders
Dry mouth
|
15.9%
10/63 • Number of events 10
|
16.9%
10/59 • Number of events 11
|
15.6%
10/64 • Number of events 10
|
19.0%
12/63 • Number of events 12
|
|
Gastrointestinal disorders
Dyspepsia
|
6.3%
4/63 • Number of events 5
|
6.8%
4/59 • Number of events 5
|
6.2%
4/64 • Number of events 4
|
3.2%
2/63 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
61.9%
39/63 • Number of events 42
|
69.5%
41/59 • Number of events 49
|
59.4%
38/64 • Number of events 43
|
61.9%
39/63 • Number of events 43
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
2/63 • Number of events 2
|
13.6%
8/59 • Number of events 8
|
12.5%
8/64 • Number of events 9
|
15.9%
10/63 • Number of events 10
|
|
General disorders
Asthenia
|
6.3%
4/63 • Number of events 4
|
1.7%
1/59 • Number of events 1
|
7.8%
5/64 • Number of events 5
|
7.9%
5/63 • Number of events 6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
17.5%
11/63 • Number of events 12
|
18.6%
11/59 • Number of events 11
|
20.3%
13/64 • Number of events 13
|
17.5%
11/63 • Number of events 11
|
|
Nervous system disorders
Dizziness
|
17.5%
11/63 • Number of events 11
|
13.6%
8/59 • Number of events 8
|
15.6%
10/64 • Number of events 10
|
11.1%
7/63 • Number of events 7
|
|
Nervous system disorders
Headache
|
17.5%
11/63 • Number of events 11
|
16.9%
10/59 • Number of events 10
|
21.9%
14/64 • Number of events 16
|
12.7%
8/63 • Number of events 8
|
|
Nervous system disorders
Sedation
|
7.9%
5/63 • Number of events 5
|
10.2%
6/59 • Number of events 6
|
7.8%
5/64 • Number of events 5
|
9.5%
6/63 • Number of events 6
|
|
Nervous system disorders
Somnolence
|
0.00%
0/63
|
6.8%
4/59 • Number of events 4
|
7.8%
5/64 • Number of events 5
|
14.3%
9/63 • Number of events 10
|
|
Nervous system disorders
Tremor
|
1.6%
1/63 • Number of events 1
|
6.8%
4/59 • Number of events 4
|
3.1%
2/64 • Number of events 2
|
3.2%
2/63 • Number of events 2
|
|
Psychiatric disorders
Anxiety
|
9.5%
6/63 • Number of events 7
|
6.8%
4/59 • Number of events 4
|
4.7%
3/64 • Number of events 3
|
9.5%
6/63 • Number of events 6
|
|
Psychiatric disorders
Insomnia
|
12.7%
8/63 • Number of events 8
|
13.6%
8/59 • Number of events 9
|
9.4%
6/64 • Number of events 6
|
7.9%
5/63 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
7.9%
5/63 • Number of events 5
|
8.5%
5/59 • Number of events 5
|
1.6%
1/64 • Number of events 1
|
7.9%
5/63 • Number of events 5
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60