Trial Outcomes & Findings for A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression (NCT NCT00422162)
NCT ID: NCT00422162
Last Updated: 2011-07-26
Results Overview
Measures the overall severity of depressive 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).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
339 participants
Primary outcome timeframe
Baseline to Week 4
Results posted on
2011-07-26
Participant Flow
Of the 392 patients who signed informed consent, 339 were randomized.
Participant milestones
| Measure |
Duloxetine (60 mg)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|
|
Overall Study
STARTED
|
167
|
172
|
|
Overall Study
Received Treatment
|
167
|
171
|
|
Overall Study
COMPLETED
|
143
|
142
|
|
Overall Study
NOT COMPLETED
|
24
|
30
|
Reasons for withdrawal
| Measure |
Duloxetine (60 mg)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|
|
Overall Study
Adverse Event
|
11
|
9
|
|
Overall Study
Lack of Efficacy
|
4
|
10
|
|
Overall Study
Withdrawal by Subject
|
7
|
6
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Non-Compliant with Protocol
|
1
|
1
|
|
Overall Study
Other
|
0
|
1
|
|
Overall Study
Didn't Receive Treatment
|
0
|
1
|
Baseline Characteristics
A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression
Baseline characteristics by cohort
| Measure |
Duloxetine (60 mg)
n=167 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=171 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Total
n=338 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
45.7 years
STANDARD_DEVIATION 13.9 • n=5 Participants
|
43.9 years
STANDARD_DEVIATION 12.7 • n=7 Participants
|
44.8 years
STANDARD_DEVIATION 13.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
118 Participants
n=5 Participants
|
133 Participants
n=7 Participants
|
251 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
49 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
64 participants
n=5 Participants
|
64 participants
n=7 Participants
|
128 participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
15 participants
n=5 Participants
|
17 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
81 participants
n=5 Participants
|
84 participants
n=7 Participants
|
165 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Previous Major Depressive Disorder Episodes
Yes
|
144 participants
n=5 Participants
|
150 participants
n=7 Participants
|
294 participants
n=5 Participants
|
|
Previous Major Depressive Disorder Episodes
No
|
23 participants
n=5 Participants
|
21 participants
n=7 Participants
|
44 participants
n=5 Participants
|
|
Race/Ethnicity
Asian
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity
Black
|
4 participants
n=5 Participants
|
8 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Race/Ethnicity
Caucasian
|
161 participants
n=5 Participants
|
163 participants
n=7 Participants
|
324 participants
n=5 Participants
|
|
Age at First Major Depressive Episode
|
36.3 years
STANDARD_DEVIATION 13.3 • n=5 Participants
|
35.6 years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
36.0 years
STANDARD_DEVIATION 12.8 • n=5 Participants
|
|
Blood Pressure
Systolic Blood Pressure
|
118.7 mm Hg
STANDARD_DEVIATION 12.4 • n=5 Participants
|
119.4 mm Hg
STANDARD_DEVIATION 14.8 • n=7 Participants
|
119.1 mm Hg
STANDARD_DEVIATION 13.7 • n=5 Participants
|
|
Blood Pressure
Diastolic Blood Pressure
|
74.6 mm Hg
STANDARD_DEVIATION 8.5 • n=5 Participants
|
74.7 mm Hg
STANDARD_DEVIATION 8.2 • n=7 Participants
|
74.7 mm Hg
STANDARD_DEVIATION 8.3 • n=5 Participants
|
|
Body Mass Index (BMI)
|
25.2 kilograms/square meter (kg/m^2)
STANDARD_DEVIATION 5.5 • n=5 Participants
|
25.5 kilograms/square meter (kg/m^2)
STANDARD_DEVIATION 5.5 • n=7 Participants
|
25.3 kilograms/square meter (kg/m^2)
STANDARD_DEVIATION 5.5 • n=5 Participants
|
|
Duration of Previous Major Depressive Disorder (MDD) Episode
|
16.4 weeks
STANDARD_DEVIATION 19.0 • n=5 Participants
|
13.7 weeks
STANDARD_DEVIATION 11.3 • n=7 Participants
|
15.0 weeks
STANDARD_DEVIATION 15.6 • n=5 Participants
|
|
Height
|
167.1 centimeters (cm)
STANDARD_DEVIATION 8.1 • n=5 Participants
|
166.5 centimeters (cm)
STANDARD_DEVIATION 7.6 • n=7 Participants
|
166.8 centimeters (cm)
STANDARD_DEVIATION 7.9 • n=5 Participants
|
|
Number of Previous Hospitalizations
|
1.3 number of hospitalizations
STANDARD_DEVIATION 1.6 • n=5 Participants
|
1.5 number of hospitalizations
STANDARD_DEVIATION 2.3 • n=7 Participants
|
1.4 number of hospitalizations
STANDARD_DEVIATION 2.0 • n=5 Participants
|
|
Number of Previous Major Depressive Disorder (MDD) Episodes
|
3.2 number of episodes
STANDARD_DEVIATION 2.7 • n=5 Participants
|
3.1 number of episodes
STANDARD_DEVIATION 3.0 • n=7 Participants
|
3.2 number of episodes
STANDARD_DEVIATION 2.9 • n=5 Participants
|
|
Pulse Rate
|
76.0 beats per minute
STANDARD_DEVIATION 8.8 • n=5 Participants
|
75.8 beats per minute
STANDARD_DEVIATION 9.2 • n=7 Participants
|
75.9 beats per minute
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Weight
|
70.4 kilograms (kg)
STANDARD_DEVIATION 16.7 • n=5 Participants
|
70.6 kilograms (kg)
STANDARD_DEVIATION 15.2 • n=7 Participants
|
70.5 kilograms (kg)
STANDARD_DEVIATION 15.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 4Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
Measures the overall severity of depressive 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).
Outcome measures
| Measure |
Duloxetine (60 mg)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Baseline
|
36.1 units on a scale
Standard Deviation 4.0
|
36.0 units on a scale
Standard Deviation 4.6
|
—
|
—
|
—
|
—
|
|
Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Change from Baseline
|
-20.1 units on a scale
Standard Deviation 10.6
|
-19.9 units on a scale
Standard Deviation 10.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Weeks 1, 2, 3, 4, 6, 8Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
The HAMD-6 (Items 1,2,7,8,10,13 from the 17-item HAMD) evaluates "core" symptoms of Major Depressive Disorder (MDD). Total scores range from 0 (normal) to 22 (severe).
Outcome measures
| Measure |
Duloxetine (60 mg)
n=96 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=70 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
n=106 Participants
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
n=64 Participants
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline
Change in Score at Week 4
|
-11.0 units on a scale
Standard Deviation 3.2
|
-3.9 units on a scale
Standard Deviation 3.3
|
-10.7 units on a scale
Standard Deviation 3.0
|
-3.8 units on a scale
Standard Deviation 3.6
|
-8.0 units on a scale
Standard Deviation 4.8
|
-8.1 units on a scale
Standard Deviation 4.7
|
|
Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline
Change in Score at Week 1
|
-3.9 units on a scale
Standard Deviation 3.7
|
-1.9 units on a scale
Standard Deviation 3.2
|
-3.3 units on a scale
Standard Deviation 3.4
|
-1.7 units on a scale
Standard Deviation 2.7
|
-3.1 units on a scale
Standard Deviation 3.6
|
-2.7 units on a scale
Standard Deviation 3.3
|
|
Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline
Change in Score at Week 2
|
-7.5 units on a scale
Standard Deviation 4.4
|
-3.4 units on a scale
Standard Deviation 3.6
|
-6.5 units on a scale
Standard Deviation 4.2
|
-3.0 units on a scale
Standard Deviation 3.1
|
-5.8 units on a scale
Standard Deviation 4.6
|
-5.2 units on a scale
Standard Deviation 4.2
|
|
Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline
Change in Score at Week 3
|
-9.4 units on a scale
Standard Deviation 3.7
|
-4.1 units on a scale
Standard Deviation 3.4
|
-8.7 units on a scale
Standard Deviation 3.6
|
-3.6 units on a scale
Standard Deviation 3.7
|
-7.2 units on a scale
Standard Deviation 4.4
|
-6.8 units on a scale
Standard Deviation 4.4
|
|
Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline
Change in Score at Week 6
|
-11.6 units on a scale
Standard Deviation 3.5
|
-6.4 units on a scale
Standard Deviation 4.4
|
-11.8 units on a scale
Standard Deviation 3.3
|
-5.5 units on a scale
Standard Deviation 4.4
|
-9.4 units on a scale
Standard Deviation 4.7
|
-9.4 units on a scale
Standard Deviation 4.8
|
|
Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline
Change in Score at Week 8
|
-12.3 units on a scale
Standard Deviation 3.4
|
-7.6 units on a scale
Standard Deviation 5.1
|
-12.5 units on a scale
Standard Deviation 3.0
|
-6.7 units on a scale
Standard Deviation 5.4
|
-10.3 units on a scale
Standard Deviation 4.8
|
-10.3 units on a scale
Standard Deviation 4.9
|
SECONDARY outcome
Timeframe: Baseline to Weeks 1, 2, 3, 4, 6, 8Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
Measures the overall severity of depressive 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).
Outcome measures
| Measure |
Duloxetine (60 mg)
n=96 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=70 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
n=106 Participants
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
n=64 Participants
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Change in Score at Week 1
|
-10.3 units on a scale
Standard Deviation 8.6
|
-5.6 units on a scale
Standard Deviation 6.2
|
-8.8 units on a scale
Standard Deviation 7.6
|
-5.6 units on a scale
Standard Deviation 6.3
|
-8.3 units on a scale
Standard Deviation 8.0
|
-7.6 units on a scale
Standard Deviation 7.3
|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Change in Score at Week 2
|
-18.7 units on a scale
Standard Deviation 9.9
|
-9.4 units on a scale
Standard Deviation 7.1
|
-16.3 units on a scale
Standard Deviation 8.4
|
-8.9 units on a scale
Standard Deviation 7.7
|
-14.7 units on a scale
Standard Deviation 9.9
|
-13.5 units on a scale
Standard Deviation 8.9
|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Change in Score at Week 3
|
-23.2 units on a scale
Standard Deviation 8.4
|
-11.1 units on a scale
Standard Deviation 6.8
|
-20.9 units on a scale
Standard Deviation 6.9
|
-10.3 units on a scale
Standard Deviation 9.1
|
-18.1 units on a scale
Standard Deviation 9.8
|
-16.9 units on a scale
Standard Deviation 9.3
|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Change in Score at Week 4
|
-27.2 units on a scale
Standard Deviation 6.5
|
-10.4 units on a scale
Standard Deviation 6.9
|
-25.5 units on a scale
Standard Deviation 5.6
|
-10.5 units on a scale
Standard Deviation 8.6
|
-20.1 units on a scale
Standard Deviation 10.6
|
-19.9 units on a scale
Standard Deviation 10.0
|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Change in Score at Week 6
|
-28.3 units on a scale
Standard Deviation 7.9
|
-16.1 units on a scale
Standard Deviation 9.4
|
-28.1 units on a scale
Standard Deviation 6.6
|
-14.8 units on a scale
Standard Deviation 10.4
|
-23.1 units on a scale
Standard Deviation 10.4
|
-23.1 units on a scale
Standard Deviation 10.5
|
|
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Change in Score at Week 8
|
-29.8 units on a scale
Standard Deviation 7.3
|
-19.0 units on a scale
Standard Deviation 11.8
|
-29.5 units on a scale
Standard Deviation 6.6
|
-17.2 units on a scale
Standard Deviation 12.3
|
-25.2 units on a scale
Standard Deviation 10.8
|
-24.9 units on a scale
Standard Deviation 10.9
|
SECONDARY outcome
Timeframe: 4 to 8 weeksPopulation: All randomized participants who received at least one dose of study drug and had a Week 4 and at least one following value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) and 6-Item Hamilton Depression Scale (HAMD-6) total scores were evaluated following dose up-titration in those patients who did not achieve the minimum 50% response for primary endpoint. MADRS is a rating scale for severity of depressive mood symptoms. Total scores range from 0 (low severity of symptoms) to 60 (high severity of symptoms). The HAMD-6, derived by the sum of HAMD-17 items 1, 2, 7, 8, 10 and 13, evaluates "core" symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe).
Outcome measures
| Measure |
Duloxetine (60 mg)
n=96 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=55 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
n=106 Participants
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
n=48 Participants
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6)
Change in MADRS Score from Week 4 to Week 6
|
-1.0 units on a scale
Standard Deviation 5.1
|
-7.2 units on a scale
Standard Deviation 6.3
|
-2.6 units on a scale
Standard Deviation 4.2
|
-5.8 units on a scale
Standard Deviation 7.0
|
—
|
—
|
|
Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6)
Change in MADRS Score from Week 4 to Week 8
|
-2.6 units on a scale
Standard Deviation 6.0
|
-10.9 units on a scale
Standard Deviation 8.8
|
-4.0 units on a scale
Standard Deviation 5.3
|
-8.9 units on a scale
Standard Deviation 9.1
|
—
|
—
|
|
Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6)
Change in HAMD-6 Score from Week 4 to Week 6
|
-0.6 units on a scale
Standard Deviation 2.7
|
-3.2 units on a scale
Standard Deviation 2.7
|
-1.1 units on a scale
Standard Deviation 1.8
|
-2.2 units on a scale
Standard Deviation 3.1
|
—
|
—
|
|
Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6)
Change in HMAD-6 Score from Week 4 to Week 8
|
-1.3 units on a scale
Standard Deviation 2.8
|
-4.7 units on a scale
Standard Deviation 3.6
|
-1.8 units on a scale
Standard Deviation 2.4
|
-3.8 units on a scale
Standard Deviation 4.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 2, 3, 4, 6, 8Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Outcome measures
| Measure |
Duloxetine (60 mg)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit
Week 0 (Baseline)
|
5.0 units on a scale
Standard Deviation 0.7
|
5.1 units on a scale
Standard Deviation 0.7
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit
Week 1
|
4.4 units on a scale
Standard Deviation 0.9
|
4.4 units on a scale
Standard Deviation 0.9
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit
Week 2
|
3.6 units on a scale
Standard Deviation 1.2
|
3.8 units on a scale
Standard Deviation 1.1
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit
Week 3
|
3.2 units on a scale
Standard Deviation 1.3
|
3.4 units on a scale
Standard Deviation 1.2
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit
Week 4
|
3.0 units on a scale
Standard Deviation 1.4
|
3.1 units on a scale
Standard Deviation 1.3
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit
Week 6
|
2.7 units on a scale
Standard Deviation 1.4
|
2.7 units on a scale
Standard Deviation 1.4
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit
Week 8
|
2.3 units on a scale
Standard Deviation 1.4
|
2.4 units on a scale
Standard Deviation 1.5
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 8Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse).
Outcome measures
| Measure |
Duloxetine (60 mg)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Clinical Global Impression of Improvement (CGI-I) at Each Visit
Week 1
|
3.1 units on a scale
Standard Deviation 0.8
|
3.2 units on a scale
Standard Deviation 0.8
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Improvement (CGI-I) at Each Visit
Week 2
|
2.5 units on a scale
Standard Deviation 1.0
|
2.6 units on a scale
Standard Deviation 0.8
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Improvement (CGI-I) at Each Visit
Week 3
|
2.3 units on a scale
Standard Deviation 0.9
|
2.3 units on a scale
Standard Deviation 0.9
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Improvement (CGI-I) at Each Visit
Week 4
|
2.3 units on a scale
Standard Deviation 1.1
|
2.1 units on a scale
Standard Deviation 1.0
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Improvement (CGI-I) at Each Visit
Week 6
|
2.0 units on a scale
Standard Deviation 1.1
|
2.0 units on a scale
Standard Deviation 1.1
|
—
|
—
|
—
|
—
|
|
Clinical Global Impression of Improvement (CGI-I) at Each Visit
Week 8
|
1.9 units on a scale
Standard Deviation 1.2
|
1.9 units on a scale
Standard Deviation 1.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 8Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).
Outcome measures
| Measure |
Duloxetine (60 mg)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Patient Global Impression of Improvement (PGI-I) Score at Each Visit
Week 1 (n=164, n=170)
|
3.0 units on a scale
Standard Deviation 1.0
|
3.1 units on a scale
Standard Deviation 0.9
|
—
|
—
|
—
|
—
|
|
Patient Global Impression of Improvement (PGI-I) Score at Each Visit
Week 2 (n=164, n=170)
|
2.6 units on a scale
Standard Deviation 1.1
|
2.6 units on a scale
Standard Deviation 0.9
|
—
|
—
|
—
|
—
|
|
Patient Global Impression of Improvement (PGI-I) Score at Each Visit
Week 3 (n=165, n=170)
|
2.3 units on a scale
Standard Deviation 1.1
|
2.4 units on a scale
Standard Deviation 1.1
|
—
|
—
|
—
|
—
|
|
Patient Global Impression of Improvement (PGI-I) Score at Each Visit
Week 4 (n=165, n=170)
|
2.3 units on a scale
Standard Deviation 1.2
|
2.2 units on a scale
Standard Deviation 1.2
|
—
|
—
|
—
|
—
|
|
Patient Global Impression of Improvement (PGI-I) Score at Each Visit
Week 6 (n=165, n=170)
|
2.1 units on a scale
Standard Deviation 1.3
|
2.0 units on a scale
Standard Deviation 1.1
|
—
|
—
|
—
|
—
|
|
Patient Global Impression of Improvement (PGI-I) Score at Each Visit
Week 8 (n=165, n=170)
|
2.0 units on a scale
Standard Deviation 1.3
|
1.9 units on a scale
Standard Deviation 1.2
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4 and 8Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
The HAMA scale measures anxiety symptoms accompanying Major Depressive Disorder (MDD). Each item of the 14-item HAMA was scored from 0 (not present) to 4 (very severe), with a resulting maximum total score of 56.
Outcome measures
| Measure |
Duloxetine (60 mg)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8
Week 0 (Baseline) (n=166, n=170)
|
26.0 units on a scale
Standard Deviation 6.4
|
27.0 units on a scale
Standard Deviation 7.0
|
—
|
—
|
—
|
—
|
|
Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8
Week 4 (n=165, n=168)
|
13.0 units on a scale
Standard Deviation 8.8
|
13.4 units on a scale
Standard Deviation 8.9
|
—
|
—
|
—
|
—
|
|
Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8
Week 8 (n=165, n=168)
|
9.6 units on a scale
Standard Deviation 8.8
|
9.8 units on a scale
Standard Deviation 9.2
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 4 to 8 weeksPopulation: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
Patients with reduction in MADRS score ≥50% after 4 weeks were to stay on previous dose of duloxetine. Those with reduction in MADRS \<50% were to receive 120 mg for remaining 4 weeks of treatment (up-titration from 60 mg to 120 mg for those randomized to 60 mg, and addition of placebo to 120 mg dose for those randomized to 120 mg). However, 2/70 patients randomized to 60 mg and then up-titrated to 120 mg after 4 weeks had reduction in MADRS ≥50% after 4 weeks, and 3/64 patients randomized to 120 mg and then given placebo in addition after 4 weeks had reduction in MADRS ≥50% after 4 weeks.
Outcome measures
| Measure |
Duloxetine (60 mg)
n=96 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=70 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
n=106 Participants
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
n=64 Participants
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Percentage of Responders
≥50% Reduction in MADRS Week 8
|
93.8 percentage of participants
|
65.7 percentage of participants
|
98.1 percentage of participants
|
54.7 percentage of participants
|
—
|
—
|
|
Percentage of Responders
≥50% Reduction in MADRS Week 4
|
100.0 percentage of participants
|
2.9 percentage of participants
|
100.0 percentage of participants
|
4.7 percentage of participants
|
—
|
—
|
|
Percentage of Responders
≥50% Reduction in MADRS Week 6
|
94.8 percentage of participants
|
52.9 percentage of participants
|
98.1 percentage of participants
|
39.1 percentage of participants
|
—
|
—
|
|
Percentage of Responders
≥50% Reduction in HAMD-6 Week 4
|
88.5 percentage of participants
|
10.0 percentage of participants
|
85.8 percentage of participants
|
12.5 percentage of participants
|
—
|
—
|
|
Percentage of Responders
≥50% Reduction in HAMD-6 Week 6
|
90.6 percentage of participants
|
47.1 percentage of participants
|
90.6 percentage of participants
|
31.3 percentage of participants
|
—
|
—
|
|
Percentage of Responders
≥50% Reduction in HAMD-6 Week 8
|
92.7 percentage of participants
|
60.0 percentage of participants
|
95.3 percentage of participants
|
46.9 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 8Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
Major Depressive Disorder remission was defined as a total MADRS score ≤12 at Week 8.
Outcome measures
| Measure |
Duloxetine (60 mg)
n=96 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=70 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
n=106 Participants
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
n=64 Participants
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Patients Reaching Remission
Remission at Week 8 - Yes
|
85 participants
|
29 participants
|
94 participants
|
18 participants
|
—
|
—
|
|
Patients Reaching Remission
Remission at Week 8 - No
|
11 participants
|
41 participants
|
12 participants
|
46 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 8Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
The RFL questionnaire is an instrument that evaluates patient's reasons for not committing suicide using a 6-point rating scale, where 1 is "not at all important" and 6 is "extremely important". The questionnaire required participants to rate how important each item would be for living, if suicide was contemplated. Mean scores could range from 0 to 6.
Outcome measures
| Measure |
Duloxetine (60 mg)
n=96 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=70 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
n=106 Participants
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
n=64 Participants
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8
Week 0 (Baseline) (n=96, n=66, n=106, n=61)
|
4.0 units on a scale
Standard Deviation 1.1
|
3.6 units on a scale
Standard Deviation 1.0
|
3.7 units on a scale
Standard Deviation 1.0
|
3.7 units on a scale
Standard Deviation 1.0
|
3.8 units on a scale
Standard Deviation 1.1
|
3.7 units on a scale
Standard Deviation 1.0
|
|
Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8
Week 8 (n=93, n=63, n=100, n=59)
|
4.6 units on a scale
Standard Deviation 0.9
|
4.0 units on a scale
Standard Deviation 1.2
|
4.6 units on a scale
Standard Deviation 0.9
|
3.8 units on a scale
Standard Deviation 1.1
|
4.4 units on a scale
Standard Deviation 1.1
|
4.3 units on a scale
Standard Deviation 1.1
|
|
Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8
Change from Baseline (n=93, n=59, n=100, n=57)
|
0.7 units on a scale
Standard Deviation 0.9
|
0.4 units on a scale
Standard Deviation 0.8
|
0.8 units on a scale
Standard Deviation 0.8
|
0.1 units on a scale
Standard Deviation 0.9
|
0.6 units on a scale
Standard Deviation 0.9
|
0.6 units on a scale
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: over 8 weeksPopulation: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward. The total number of patients with hypnotics and anxiolytics concomitant therapies was 125 (Duloxetine 60mg) and 123 (Duloxetine 120mg).
Number of participants using medication for anxiety and sleep disturbances.
Outcome measures
| Measure |
Duloxetine (60 mg)
n=166 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=170 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken Before Start of Study (Week -1)
|
65 participants
|
59 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken Between Week -1 and Week 0
|
93 participants
|
88 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken Between Week 0 and Week 1
|
95 participants
|
89 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken Between Week 1 and Week 2
|
80 participants
|
84 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken Between Week 2 and Week 3
|
62 participants
|
67 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken Between Week 3 and Week 4
|
55 participants
|
58 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken Between Week 4 and Week 6
|
47 participants
|
49 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken Between Week 6 and Week 8
|
51 participants
|
52 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Taken After Week 8
|
18 participants
|
10 participants
|
—
|
—
|
—
|
—
|
|
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Medication Not Taken Between Consecutive Visits
|
8 participants
|
8 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: over 8 weeksPopulation: All randomized participants with at least one dose of study drug.
Laboratory results that were potentially clinically significant.
Outcome measures
| Measure |
Duloxetine (60 mg)
n=167 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=171 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Decreased Sodium (n=160, n=163)
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Decreased Haematocrit (n=155, n=159)
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Decreased Haemoglobin (n=156, n=160)
|
2 participants
|
2 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Decreased Red Cell Count (n=156, n=160)
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Mean Cell Volume (n=155, n=159)
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Decreased White Cell Count (n=156, n=160)
|
1 participants
|
2 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Potassium (n=159, n=163)
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Aspartate Transaminase (n=158, n=161)
|
2 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Alanine Transaminase (n=159, n=161)
|
3 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Alkaline Phosphatase (n=161, n=163)
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Gamma-Glutamyl Transferase (n=161,n=163)
|
2 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Creatine Kinase (n=159, n=161)
|
6 participants
|
3 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Decreased Glucose (n=158, n=162)
|
1 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Cholesterol (n=160, n=163)
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Total Bilirubin (n=159, n=161)
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Increased Uric Acid (n=160, n=163)
|
0 participants
|
2 participants
|
—
|
—
|
—
|
—
|
|
Number of Patients With Potentially Clinically Significant Laboratory Findings
Decreased Albumin (n=158, n=161)
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: over 8 weeksPopulation: All randomized participants with at least one dose of study drug.
Listing of adverse events (AE) that led to treatment discontinuation (DC).
Outcome measures
| Measure |
Duloxetine (60 mg)
n=167 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=171 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Discontinuations Due to Adverse Events (AE)
Renal Failure
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Total Number of Patients With AEs Leading to DC
|
11 participants
|
9 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Suicide Attempt
|
3 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Suicidal Ideation
|
2 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Hypothyroidism
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Depression
|
1 participants
|
2 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Major Depression
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Psychotic Disorder
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Schizoaffective Disorder
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Self-Injurious Behaviour
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Headache
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Nausea
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Irritability
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Brain Neoplasm
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Dizziness
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Sedation
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Serotonin Syndrome
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Upper Abdominal Pain
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Drug Eruption
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
|
Discontinuations Due to Adverse Events (AE)
Urinary Retention
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: over 8 weeksPopulation: All randomized participants with at least one dose of study drug.
Systolic and diastolic blood pressure and pulse rate were measured after 2 minutes rest in a supine position. High values were: diastolic blood pressure ≥90 mm Hg and increase from baseline of ≥10 mm Hg; systolic blood pressure ≥140 mm Hg and increase from baseline of ≥10 mm Hg; pulse rate ≥100 beats per minute (bpm) and an increase of ≥10 bpm from baseline.
Outcome measures
| Measure |
Duloxetine (60 mg)
n=167 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=171 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study
High Systolic Blood Pressure
|
23 participants
|
25 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study
High Diastolic Blood Pressure
|
28 participants
|
37 participants
|
—
|
—
|
—
|
—
|
|
Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study
High Pulse Rate
|
10 participants
|
14 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Weeks 4 and 8Population: All randomized participants with at least one dose of study drug and a baseline and at least one post-baseline value. Last observation carried forward.
Change in weight = Post-baseline visit minus baseline.
Outcome measures
| Measure |
Duloxetine (60 mg)
n=167 Participants
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
n=171 Participants
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
Duloxetine 120 mg Responder
60mg BID for 8 weeks
|
Duloxetine 120 mg Non-Responder
60mg BID for 8 weeks (placebo added at Week 4)
|
Duloxetine 60 mg (All)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine 120 mg (All)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|---|---|---|---|
|
Change From Baseline to Week 4 and Week 8 in Weight
Change from Baseline to Week 4 (n=163,n=167)
|
0.1 kilograms
Standard Deviation 2.0
|
0.0 kilograms
Standard Deviation 2.3
|
—
|
—
|
—
|
—
|
|
Change From Baseline to Week 4 and Week 8 in Weight
Change from Baseline to Week 8 (n=163, n=168)
|
0.5 kilograms
Standard Deviation 2.9
|
0.1 kilograms
Standard Deviation 2.8
|
—
|
—
|
—
|
—
|
Adverse Events
Duloxetine (60 mg)
Serious events: 7 serious events
Other events: 95 other events
Deaths: 0 deaths
Duloxetine (120 mg)
Serious events: 6 serious events
Other events: 85 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Duloxetine (60 mg)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|
|
General disorders
Irritability
|
0.60%
1/167 • Number of events 1
|
0.00%
0/171
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.60%
1/167 • Number of events 1
|
0.00%
0/171
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
|
0.00%
0/167
|
0.58%
1/171 • Number of events 1
|
|
Nervous system disorders
Serotonin syndrome
|
0.00%
0/167
|
0.58%
1/171 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/167
|
1.2%
2/171 • Number of events 2
|
|
Psychiatric disorders
Depression
|
0.00%
0/167
|
1.2%
2/171 • Number of events 2
|
|
Psychiatric disorders
Self injurious behaviour
|
0.60%
1/167 • Number of events 1
|
0.00%
0/171
|
|
Psychiatric disorders
Suicidal ideation
|
1.8%
3/167 • Number of events 3
|
0.00%
0/171
|
|
Psychiatric disorders
Suicide attempt
|
2.4%
4/167 • Number of events 4
|
0.00%
0/171
|
Other adverse events
| Measure |
Duloxetine (60 mg)
60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks
|
Duloxetine (120 mg)
60mg BID for 8 weeks (placebo added at Week 4 for nonresponders)
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
4.8%
8/167 • Number of events 8
|
9.4%
16/171 • Number of events 21
|
|
Gastrointestinal disorders
Diarrhoea
|
4.2%
7/167 • Number of events 7
|
2.3%
4/171 • Number of events 4
|
|
Gastrointestinal disorders
Dry mouth
|
4.8%
8/167 • Number of events 8
|
7.0%
12/171 • Number of events 14
|
|
Gastrointestinal disorders
Nausea
|
22.2%
37/167 • Number of events 42
|
12.3%
21/171 • Number of events 25
|
|
Infections and infestations
Nasopharyngitis
|
2.4%
4/167 • Number of events 6
|
5.3%
9/171 • Number of events 9
|
|
Nervous system disorders
Headache
|
15.6%
26/167 • Number of events 37
|
11.1%
19/171 • Number of events 19
|
|
Nervous system disorders
Tremor
|
1.8%
3/167 • Number of events 3
|
4.7%
8/171 • Number of events 8
|
|
Psychiatric disorders
Insomnia
|
2.4%
4/167 • Number of events 8
|
4.1%
7/171 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.4%
9/167 • Number of events 9
|
2.9%
5/171 • Number of events 6
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60