Trial Outcomes & Findings for A Study in the Treatment of Children and Adolescents With Major Depressive Disorder (NCT NCT00849901)
NCT ID: NCT00849901
Last Updated: 2017-09-11
Results Overview
CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. Least Square (LS) means are adjusted for baseline, pooled investigator, age category, visit, treatment, treatment\*visit, age category\*visit and baseline\*visit.
COMPLETED
PHASE3
337 participants
Baseline, Week 10
2017-09-11
Participant Flow
This study consisted of a 10-week acute treatment phase, and a 6-month extension phase.
Participant milestones
| Measure |
Duloxetine/Duloxetine
Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase
|
Fluoxetine/Fluoxetine
Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase
|
Placebo/Duloxetine
Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
|
|---|---|---|---|
|
Acute Treatment Phase
STARTED
|
117
|
117
|
103
|
|
Acute Treatment Phase
COMPLETED
|
87
|
91
|
87
|
|
Acute Treatment Phase
NOT COMPLETED
|
30
|
26
|
16
|
|
Extension Phase
STARTED
|
83
|
91
|
86
|
|
Extension Phase
COMPLETED
|
56
|
65
|
69
|
|
Extension Phase
NOT COMPLETED
|
27
|
26
|
17
|
Reasons for withdrawal
| Measure |
Duloxetine/Duloxetine
Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase
|
Fluoxetine/Fluoxetine
Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase
|
Placebo/Duloxetine
Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
|
|---|---|---|---|
|
Acute Treatment Phase
Adverse Event
|
9
|
1
|
3
|
|
Acute Treatment Phase
Lost to Follow-up
|
2
|
4
|
1
|
|
Acute Treatment Phase
Protocol Violation
|
0
|
2
|
1
|
|
Acute Treatment Phase
Withdrawal by Subject
|
4
|
10
|
4
|
|
Acute Treatment Phase
Parent or Caregiver Decision
|
11
|
5
|
4
|
|
Acute Treatment Phase
Physician Decision
|
1
|
1
|
1
|
|
Acute Treatment Phase
Sponsor Decision
|
1
|
0
|
0
|
|
Acute Treatment Phase
Lack of Efficacy
|
2
|
3
|
2
|
|
Extension Phase
Adverse Event
|
2
|
8
|
4
|
|
Extension Phase
Lost to Follow-up
|
3
|
0
|
1
|
|
Extension Phase
Protocol Violation
|
2
|
2
|
4
|
|
Extension Phase
Withdrawal by Subject
|
7
|
6
|
3
|
|
Extension Phase
Parent or Caregiver Decision
|
10
|
4
|
4
|
|
Extension Phase
Physician Decision
|
1
|
2
|
0
|
|
Extension Phase
Lack of Efficacy
|
2
|
4
|
1
|
Baseline Characteristics
A Study in the Treatment of Children and Adolescents With Major Depressive Disorder
Baseline characteristics by cohort
| Measure |
Duloxetine/Duloxetine
n=117 Participants
Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase
|
Fluoxetine/Fluoxetine
n=117 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase
|
Placebo/Duloxetine
n=103 Participants
Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
|
Total
n=337 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
13.14 years
STANDARD_DEVIATION 3.043 • n=5 Participants
|
13.08 years
STANDARD_DEVIATION 3.272 • n=7 Participants
|
13.28 years
STANDARD_DEVIATION 3.055 • n=5 Participants
|
13.16 years
STANDARD_DEVIATION 3.120 • n=4 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
176 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
53 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
161 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
17 participants
n=5 Participants
|
9 participants
n=7 Participants
|
13 participants
n=5 Participants
|
39 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
90 participants
n=5 Participants
|
93 participants
n=7 Participants
|
79 participants
n=5 Participants
|
262 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Multiracial
|
4 participants
n=5 Participants
|
7 participants
n=7 Participants
|
5 participants
n=5 Participants
|
16 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Provided
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5 participants
n=5 Participants
|
15 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=5 Participants
|
45 participants
n=7 Participants
|
45 participants
n=5 Participants
|
140 participants
n=4 Participants
|
|
Region of Enrollment
Finland
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
0 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Region of Enrollment
France
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
8 participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Region of Enrollment
Slovakia
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
1 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Region of Enrollment
Ukraine
|
25 participants
n=5 Participants
|
23 participants
n=7 Participants
|
18 participants
n=5 Participants
|
66 participants
n=4 Participants
|
|
Region of Enrollment
Russian Federation
|
13 participants
n=5 Participants
|
15 participants
n=7 Participants
|
12 participants
n=5 Participants
|
40 participants
n=4 Participants
|
|
Region of Enrollment
Estonia
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
South Africa
|
21 participants
n=5 Participants
|
24 participants
n=7 Participants
|
22 participants
n=5 Participants
|
67 participants
n=4 Participants
|
|
Children's Depression Rating Scale-Revised (CDRS-R) Total Score
|
59.2 units on a scale
STANDARD_DEVIATION 10.45 • n=5 Participants
|
58.8 units on a scale
STANDARD_DEVIATION 10.56 • n=7 Participants
|
60.2 units on a scale
STANDARD_DEVIATION 11.67 • n=5 Participants
|
59.4 units on a scale
STANDARD_DEVIATION 10.85 • n=4 Participants
|
|
CDRS-R Subscale Scores
Mood
|
16.3 units on a scale
STANDARD_DEVIATION 3.54 • n=5 Participants
|
15.9 units on a scale
STANDARD_DEVIATION 3.85 • n=7 Participants
|
16.1 units on a scale
STANDARD_DEVIATION 3.59 • n=5 Participants
|
16.1 units on a scale
STANDARD_DEVIATION 3.66 • n=4 Participants
|
|
CDRS-R Subscale Scores
Somatic
|
19.8 units on a scale
STANDARD_DEVIATION 4.54 • n=5 Participants
|
19.7 units on a scale
STANDARD_DEVIATION 4.21 • n=7 Participants
|
20.0 units on a scale
STANDARD_DEVIATION 4.75 • n=5 Participants
|
19.8 units on a scale
STANDARD_DEVIATION 4.48 • n=4 Participants
|
|
CDRS-R Subscale Scores
Subjective
|
10.1 units on a scale
STANDARD_DEVIATION 3.08 • n=5 Participants
|
10.4 units on a scale
STANDARD_DEVIATION 3.24 • n=7 Participants
|
10.4 units on a scale
STANDARD_DEVIATION 3.46 • n=5 Participants
|
10.3 units on a scale
STANDARD_DEVIATION 3.25 • n=4 Participants
|
|
CDRS-R Subscale Scores
Behavior
|
13.0 units on a scale
STANDARD_DEVIATION 2.79 • n=5 Participants
|
12.8 units on a scale
STANDARD_DEVIATION 2.87 • n=7 Participants
|
13.5 units on a scale
STANDARD_DEVIATION 3.00 • n=5 Participants
|
13.1 units on a scale
STANDARD_DEVIATION 2.89 • n=4 Participants
|
|
Clinical Global Impressions of Severity (CGI-Severity) score
|
4.5 units on a scale
STANDARD_DEVIATION 0.62 • n=5 Participants
|
4.5 units on a scale
STANDARD_DEVIATION 0.58 • n=7 Participants
|
4.6 units on a scale
STANDARD_DEVIATION 0.65 • n=5 Participants
|
4.5 units on a scale
STANDARD_DEVIATION 0.62 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 10Population: Participants with both a baseline and at least one post-baseline value.
CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. Least Square (LS) means are adjusted for baseline, pooled investigator, age category, visit, treatment, treatment\*visit, age category\*visit and baseline\*visit.
Outcome measures
| Measure |
Duloxetine
n=113 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=113 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=103 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint
|
-24.3 units on a scale
Standard Error 1.09
|
-23.7 units on a scale
Standard Error 1.06
|
-24.3 units on a scale
Standard Error 1.11
|
SECONDARY outcome
Timeframe: Week 10, Week 36Population: Participants with value during treatment phase and at least one post-Week 10 value.
CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. LS means are adjusted for baseline, pooled investigator, age category, visit, age category\*visit and baseline\*visit.
Outcome measures
| Measure |
Duloxetine
n=81 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=91 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=85 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint
|
-7.2 units on a scale
Standard Deviation 0.86
|
-9.9 units on a scale
Standard Deviation 0.72
|
-9.6 units on a scale
Standard Deviation 0.86
|
SECONDARY outcome
Timeframe: Baseline, Week 10Population: Participants with both a baseline and at least one post-baseline value.
CDRS-R Subscale scores include Mood (Sum of items 8, 11, 14, 15), Somatic (Sum of items 4-7, 16, 17), Subjective (Sum of items 9, 10, 12, 13) and Behavior (Sum of items 1-3). Mood and Subjective subscale scores range from 4 to 28; Somatic subscale scores range from 6 to 36; Behavior subscale scores range from 3 to 21. Higher score indicates greater severity of disease. LS means are adjusted for baseline, pooled investigator, age category, visit, treatment, treatment\*visit, age category\*visit and baseline\*visit.
Outcome measures
| Measure |
Duloxetine
n=113 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=113 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=103 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint
Mood (N=113, 113, 103)
|
-7.0 units on a scale
Standard Error 0.36
|
-7.1 units on a scale
Standard Error 0.35
|
-7.0 units on a scale
Standard Error 0.37
|
|
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint
Somatic (N=113, 113, 103)
|
-7.7 units on a scale
Standard Error 0.42
|
-7.6 units on a scale
Standard Error 0.41
|
-7.7 units on a scale
Standard Error 0.42
|
|
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint
Subjective (N=113, 113, 103)
|
-4.0 units on a scale
Standard Error 0.23
|
-3.6 units on a scale
Standard Error 0.22
|
-4.0 units on a scale
Standard Error 0.23
|
|
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint
Behavior (N=113, 112, 103)
|
-5.6 units on a scale
Standard Error 0.30
|
-5.4 units on a scale
Standard Error 0.30
|
-5.7 units on a scale
Standard Error 0.31
|
SECONDARY outcome
Timeframe: Week 10, Week 36Population: Participants with value during treatment phase and at least one post-Week 10 value.
CDRS-R Subscale scores include Mood (Sum of items 8, 11, 14, 15), Somatic (Sum of items 4-7, 16, 17), Subjective (Sum of items 9, 10, 12, 13) and Behavior (Sum of items 1-3). Mood and Subjective subscale scores range from 4 to 28; Somatic subscale scores range from 6 to 36; Behavior subscale scores range from 3 to 21. Higher score indicates greater severity of disease. LS means are adjusted for baseline, pooled investigator, age category, visit, age category\*visit and baseline\*visit.
Outcome measures
| Measure |
Duloxetine
n=81 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=91 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=85 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint
Mood
|
-1.9 units on a scale
Standard Error 0.34
|
-2.5 units on a scale
Standard Error 0.24
|
-2.9 units on a scale
Standard Error 0.29
|
|
Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint
Somatic
|
-2.8 units on a scale
Standard Error 0.35
|
-3.6 units on a scale
Standard Error 0.27
|
-3.2 units on a scale
Standard Error 0.33
|
|
Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint
Subjective
|
-0.3 units on a scale
Standard Error 0.24
|
-1.3 units on a scale
Standard Error 0.13
|
-1.2 units on a scale
Standard Error 0.17
|
|
Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint
Behavior
|
-1.9 units on a scale
Standard Error 0.23
|
-2.8 units on a scale
Standard Error 0.20
|
-2.1 units on a scale
Standard Error 0.36
|
SECONDARY outcome
Timeframe: Baseline, Week 10Population: Participants with both a baseline and at least one post-baseline value.
CGI-Severity evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). LS means are adjusted for baseline, pooled investigator, age category, visit, treatment, treatment\*visit, age category\*visit and baseline\*visit.
Outcome measures
| Measure |
Duloxetine
n=113 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=113 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=110 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint
|
-1.9 units on a scale
Standard Error 0.11
|
-1.8 units on a scale
Standard Error 0.10
|
-1.9 units on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Week 10, Week 36Population: Participants with value during treatment phase and at least one post-Week 10 value.
CGI-Severity evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). LS means are adjusted for baseline, pooled investigator, age category, visit, age category\*visit and baseline\*visit.
Outcome measures
| Measure |
Duloxetine
n=81 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=91 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=85 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint
|
-0.6 units on a scale
Standard Error 0.12
|
-1.0 units on a scale
Standard Error 0.07
|
-1.1 units on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Baseline through Week 10Population: Participants with at least one post-baseline C-SSRS suicidal ideation or suicidal behavior score and who are at risk for treatment emergent suicidal ideation or behavior.
Columbia Suicide Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Treatment Emergent Suicidal Ideation is worsening or new occurrence of events during treatment compared to lead-in baseline (Week -1 - 0).
Outcome measures
| Measure |
Duloxetine
n=113 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=113 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=103 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10
Suicidal Ideation
|
16 participants
|
16 participants
|
15 participants
|
|
Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10
Suicidal Behavior
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10
Treatment Emergent Suicidal Ideation
|
8 participants
|
9 participants
|
7 participants
|
SECONDARY outcome
Timeframe: Week 10 through Week 36Population: Participants with at least one post-baseline C-SSRS suicidal ideation or suicidal behavior score and who are at risk for treatment emergent suicidal ideation or behavior.
Columbia Suicide Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Treatment Emergent Suicidal Ideation is worsening or new occurrence of events during treatment compared to lead-in baseline (Week 7-10).
Outcome measures
| Measure |
Duloxetine
n=81 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=91 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=85 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36
Suicidal Ideation
|
13 participants
|
13 participants
|
8 participants
|
|
Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36
Suicidal Behavior
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36
Treatment Emergent Suicidal Ideation
|
9 participants
|
13 participants
|
8 participants
|
SECONDARY outcome
Timeframe: Baseline through Week 10Population: Participants with normal ALT value (ALT \<1 x ULN) at last non-missing baseline visit and at least one non-missing post-baseline value.
Total number of participants with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Potentially clinically significant hepatic laboratory results at any time are defined as alanine transaminase (ALT) ≥3 x upper limit of normal (ULN), ALT ≥5 x ULN and ALT ≥10 x ULN, as well as ALT ≥3 x ULN and Total Bilirubin ≥2 x ULN.
Outcome measures
| Measure |
Duloxetine
n=101 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=102 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=94 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10
ALT≥3 x ULN
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10
ALT≥5 x ULN
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10
ALT≥10 x ULN
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10
ALT≥3 x ULN and Total Bilirubin≥2 x ULN
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Week 10 through Week 36Population: Participants with normal ALT value (ALT\<1 x ULN) at last non-missing visit before Week 10 and at least one non-missing post-Week 10 value.
Total number of participants with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Potentially clinically significant hepatic laboratory results at any time are defined as alanine transaminase (ALT) ≥3 x upper limit of normal (ULN), ALT ≥5 x ULN and ALT ≥10 x ULN, as well as ALT ≥3 x ULN and Total Bilirubin ≥2 x ULN.
Outcome measures
| Measure |
Duloxetine
n=77 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=83 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=82 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36
ALT≥3 x ULN
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36
ALT≥5 x ULN
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36
ALT≥10 x ULN
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36
ALT≥3 x ULN and Total Bilirubin≥2 x ULN
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline through Week 10Population: Participants with normal baseline value and at least one post-baseline value, and who were at risk for the specific PCS criteria.
PCS increase in systolic and diastolic BP was defined as increase of ≥5 millimeter mercury (mm Hg) from baseline (BL) high value to a value above the 95th percentile at post-BL; PCS increase of pulse was defined as \>140 and increase of ≥15 from BL high value for age 7-11 and \>120 and increase of ≥15 from BL high value for age 12-17; PCS decrease of pulse was defined as \<60 and a decrease of ≥25 from BL low value for age 7-11 and \<50 and a decrease of ≥15 from BL low value for age 12-17; PCS decrease of weight was defined as decrease of at least 3.5% from BL low value.
Outcome measures
| Measure |
Duloxetine
n=117 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=117 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=103 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10
Diastolic BP Increase (N=102, 106, 93)
|
8.8 percentage of participants
|
7.5 percentage of participants
|
17.2 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10
Systolic BP Increase (N=100, 106, 90)
|
7.0 percentage of participants
|
5.7 percentage of participants
|
6.7 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10
Pulse Decrease (N=111, 112, 102)
|
0.9 percentage of participants
|
0.9 percentage of participants
|
1.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10
Pulse Increase (N=113, 114, 103)
|
0 percentage of participants
|
0 percentage of participants
|
1.0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10
Weight Decrease (N=113, 114, 103)
|
12.4 percentage of participants
|
11.4 percentage of participants
|
4.9 percentage of participants
|
SECONDARY outcome
Timeframe: Week 10 through Week 36Population: Participants with normal value at last non-missing visit before Week 10 and at least one non-missing post-Week 10 value, and who are at risk for the specific PCS criteria.
PCS increase in systolic and diastolic BP was defined as increase of ≥ 5mm Hg from baseline (BL) high value to a value above the 95th percentile at post-BL; PCS increase of pulse was defined as \>140 and increase of ≥15 from BL high value for age 7-11 and \>120 and increase of ≥15 from BL high value for age 12-17; PCS decrease of pulse was defined as \<60 and a decrease of ≥25 from BL low value for age 7-11 and \<50 and a decrease of ≥15 from BL low value for age 12-17; PCS decrease of weight was defined as decrease of at least 3.5% from BL low value.
Outcome measures
| Measure |
Duloxetine
n=83 Participants
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine
n=91 Participants
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo
n=86 Participants
Received placebo PO, QD during acute treatment phase
|
|---|---|---|---|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36
Diastolic BP Increase (N=65, 76, 61)
|
16.9 percentage of participants
|
11.8 percentage of participants
|
4.9 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36
Systolic BP Increase (N=64, 80, 69)
|
12.5 percentage of participants
|
12.5 percentage of participants
|
10.1 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36
Pulse Decrease (N=78, 84, 82)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36
Pulse Increase (N=81, 91, 84)
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36
Weight Decrease (N=81, 91, 85)
|
6.2 percentage of participants
|
3.3 percentage of participants
|
9.4 percentage of participants
|
Adverse Events
Fluoxetine - Extension
Placebo/Duloxetine - Extension
Duloxetine - Acute
Fluoxetine - Acute
Placebo - Acute
Duloxetine - Extension
Serious adverse events
| Measure |
Fluoxetine - Extension
n=92 participants at risk
Received fluoxetine 20 and/or 40 mg PO, QD during extension phase. One participant had discontinued the acute phase due to an adverse event but was accidentally dispensed drug at the last visit of the acute phase, thus based on intent-to-treat principal, this participant was included in the extension phase analyses for adverse events (AEs) (resulting in one more participant being analyzed for AEs than started the extension phase in the Participant Flow section).
|
Placebo/Duloxetine - Extension
n=86 participants at risk
Received duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
|
Duloxetine - Acute
n=117 participants at risk
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine - Acute
n=117 participants at risk
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo - Acute
n=103 participants at risk
Received placebo PO, QD during acute treatment phase
|
Duloxetine - Extension
n=83 participants at risk
Received duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.00%
0/92
|
0.00%
0/86
|
0.00%
0/117
|
0.85%
1/117 • Number of events 1
|
0.00%
0/103
|
0.00%
0/83
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/92
|
0.00%
0/86
|
0.00%
0/117
|
0.85%
1/117 • Number of events 1
|
0.00%
0/103
|
0.00%
0/83
|
|
Infections and infestations
Pilonidal cyst
|
0.00%
0/92
|
1.2%
1/86 • Number of events 1
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Infections and infestations
Pneumonia
|
0.00%
0/92
|
0.00%
0/86
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
1.2%
1/83 • Number of events 1
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
1.1%
1/92 • Number of events 1
|
0.00%
0/86
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.00%
0/92
|
0.00%
0/86
|
0.00%
0/117
|
0.85%
1/117 • Number of events 1
|
0.00%
0/103
|
0.00%
0/83
|
|
Nervous system disorders
Convulsion
|
1.1%
1/92 • Number of events 1
|
0.00%
0/86
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Nervous system disorders
Epilepsy
|
1.1%
1/92 • Number of events 1
|
0.00%
0/86
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Nervous system disorders
Syncope
|
0.00%
0/92
|
0.00%
0/86
|
0.85%
1/117 • Number of events 1
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Adjustment disorder with disturbance of conduct
|
1.1%
1/92 • Number of events 1
|
0.00%
0/86
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Conversion disorder
|
0.00%
0/92
|
1.2%
1/86 • Number of events 1
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Drug abuse
|
0.00%
0/92
|
0.00%
0/86
|
0.85%
1/117 • Number of events 1
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Hypomania
|
1.1%
1/92 • Number of events 1
|
0.00%
0/86
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Major depression
|
0.00%
0/92
|
1.2%
1/86 • Number of events 1
|
0.00%
0/117
|
0.00%
0/117
|
0.97%
1/103 • Number of events 1
|
0.00%
0/83
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/92
|
0.00%
0/86
|
0.85%
1/117 • Number of events 1
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/92
|
1.2%
1/86 • Number of events 1
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Social phobia
|
0.00%
0/92
|
0.00%
0/86
|
0.85%
1/117 • Number of events 1
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/92
|
1.2%
1/86 • Number of events 1
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
|
Psychiatric disorders
Suicide attempt
|
1.1%
1/92 • Number of events 1
|
0.00%
0/86
|
0.00%
0/117
|
0.00%
0/117
|
0.00%
0/103
|
0.00%
0/83
|
Other adverse events
| Measure |
Fluoxetine - Extension
n=92 participants at risk
Received fluoxetine 20 and/or 40 mg PO, QD during extension phase. One participant had discontinued the acute phase due to an adverse event but was accidentally dispensed drug at the last visit of the acute phase, thus based on intent-to-treat principal, this participant was included in the extension phase analyses for adverse events (AEs) (resulting in one more participant being analyzed for AEs than started the extension phase in the Participant Flow section).
|
Placebo/Duloxetine - Extension
n=86 participants at risk
Received duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
|
Duloxetine - Acute
n=117 participants at risk
Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase
|
Fluoxetine - Acute
n=117 participants at risk
Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase
|
Placebo - Acute
n=103 participants at risk
Received placebo PO, QD during acute treatment phase
|
Duloxetine - Extension
n=83 participants at risk
Received duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
2.2%
2/92 • Number of events 2
|
1.2%
1/86 • Number of events 1
|
0.85%
1/117 • Number of events 1
|
1.7%
2/117 • Number of events 2
|
4.9%
5/103 • Number of events 5
|
1.2%
1/83 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.2%
2/92 • Number of events 2
|
8.1%
7/86 • Number of events 7
|
3.4%
4/117 • Number of events 4
|
4.3%
5/117 • Number of events 7
|
6.8%
7/103 • Number of events 8
|
1.2%
1/83 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
4.3%
4/92 • Number of events 4
|
2.3%
2/86 • Number of events 2
|
5.1%
6/117 • Number of events 6
|
1.7%
2/117 • Number of events 2
|
1.9%
2/103 • Number of events 2
|
3.6%
3/83 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
7.6%
7/92 • Number of events 8
|
14.0%
12/86 • Number of events 17
|
17.1%
20/117 • Number of events 28
|
12.8%
15/117 • Number of events 17
|
10.7%
11/103 • Number of events 14
|
3.6%
3/83 • Number of events 6
|
|
Gastrointestinal disorders
Vomiting
|
5.4%
5/92 • Number of events 5
|
9.3%
8/86 • Number of events 9
|
6.0%
7/117 • Number of events 7
|
5.1%
6/117 • Number of events 7
|
2.9%
3/103 • Number of events 3
|
4.8%
4/83 • Number of events 5
|
|
General disorders
Fatigue
|
3.3%
3/92 • Number of events 3
|
4.7%
4/86 • Number of events 4
|
6.8%
8/117 • Number of events 8
|
2.6%
3/117 • Number of events 5
|
4.9%
5/103 • Number of events 5
|
1.2%
1/83 • Number of events 1
|
|
Infections and infestations
Gastroenteritis
|
2.2%
2/92 • Number of events 2
|
3.5%
3/86 • Number of events 3
|
0.00%
0/117
|
0.85%
1/117 • Number of events 1
|
1.9%
2/103 • Number of events 2
|
4.8%
4/83 • Number of events 4
|
|
Infections and infestations
Influenza
|
3.3%
3/92 • Number of events 3
|
4.7%
4/86 • Number of events 4
|
6.0%
7/117 • Number of events 7
|
2.6%
3/117 • Number of events 3
|
5.8%
6/103 • Number of events 8
|
6.0%
5/83 • Number of events 6
|
|
Infections and infestations
Nasopharyngitis
|
8.7%
8/92 • Number of events 12
|
10.5%
9/86 • Number of events 9
|
1.7%
2/117 • Number of events 2
|
3.4%
4/117 • Number of events 4
|
4.9%
5/103 • Number of events 5
|
10.8%
9/83 • Number of events 9
|
|
Infections and infestations
Sinusitis
|
1.1%
1/92 • Number of events 1
|
1.2%
1/86 • Number of events 1
|
0.85%
1/117 • Number of events 1
|
0.85%
1/117 • Number of events 1
|
2.9%
3/103 • Number of events 3
|
4.8%
4/83 • Number of events 4
|
|
Infections and infestations
Upper respiratory tract infection
|
5.4%
5/92 • Number of events 7
|
3.5%
3/86 • Number of events 3
|
3.4%
4/117 • Number of events 4
|
2.6%
3/117 • Number of events 3
|
0.97%
1/103 • Number of events 1
|
6.0%
5/83 • Number of events 6
|
|
Injury, poisoning and procedural complications
Incorrect dose administered
|
3.3%
3/92 • Number of events 3
|
0.00%
0/86
|
1.7%
2/117 • Number of events 2
|
3.4%
4/117 • Number of events 5
|
2.9%
3/103 • Number of events 3
|
4.8%
4/83 • Number of events 5
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/92
|
3.5%
3/86 • Number of events 3
|
8.5%
10/117 • Number of events 11
|
8.5%
10/117 • Number of events 10
|
6.8%
7/103 • Number of events 7
|
2.4%
2/83 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
3.3%
3/92 • Number of events 3
|
7.0%
6/86 • Number of events 6
|
8.5%
10/117 • Number of events 11
|
3.4%
4/117 • Number of events 4
|
2.9%
3/103 • Number of events 3
|
3.6%
3/83 • Number of events 3
|
|
Nervous system disorders
Headache
|
9.8%
9/92 • Number of events 10
|
11.6%
10/86 • Number of events 12
|
16.2%
19/117 • Number of events 23
|
15.4%
18/117 • Number of events 22
|
8.7%
9/103 • Number of events 10
|
10.8%
9/83 • Number of events 10
|
|
Nervous system disorders
Somnolence
|
4.3%
4/92 • Number of events 5
|
3.5%
3/86 • Number of events 4
|
6.0%
7/117 • Number of events 7
|
5.1%
6/117 • Number of events 6
|
5.8%
6/103 • Number of events 6
|
2.4%
2/83 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/92
|
1.2%
1/86 • Number of events 1
|
5.1%
6/117 • Number of events 8
|
5.1%
6/117 • Number of events 6
|
1.9%
2/103 • Number of events 2
|
0.00%
0/83
|
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