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A Study in the Treatment of Children and Adolescents With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT00849693
Recruitment Status : Completed
First Posted : February 24, 2009
Results First Posted : April 19, 2012
Last Update Posted : April 19, 2012
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Placebo
Drug: fluoxetine
Drug: duloxetine
Enrollment 463
Recruitment Details  
Pre-assignment Details This study consisted of a 10-week acute treatment phase, and a 6-month extension phase.
Arm/Group Title Duloxetine 60 mg / Duloxetine 60-120 mg Duloxetine 30 mg/Duloxetine 60-120 mg Fluoxetine 20 mg/Fluoxetine 20-40 mg Placebo/Duloxetine 60-120 mg
Hide Arm/Group Description Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase Participants were treated with Duloxetine 30 mg orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase and Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Period Title: Acute Treatment Phase
Started 108 116 117 122
Completed 75 [1] 81 [2] 84 85 [3]
Not Completed 33 35 33 37
Reason Not Completed
Adverse Event             12             7             6             4
Lost to Follow-up             5             8             11             9
Protocol Violation             1             5             2             6
Withdrawal by Subject             5             5             3             8
Parent or caregiver decision             7             6             7             7
Physician Decision             2             1             2             1
Sponsor decision             0             0             1             0
Lack of Efficacy             1             3             1             2
[1]
2 didn't enter extension phase.
[2]
1 didn't enter extension phase
[3]
3 didn't enter extension phase
Period Title: Extension Phase
Started 73 80 84 82
Completed 43 50 49 44
Not Completed 30 30 35 38
Reason Not Completed
Adverse Event             4             6             3             7
Lost to Follow-up             7             5             6             6
Protocol Violation             0             3             2             3
Withdrawal by Subject             6             9             10             15
Parent or caregiver decision             9             4             10             5
Physician Decision             1             1             2             0
Sponsor decision             1             0             0             1
Lack of Efficacy             2             2             2             1
Arm/Group Title Duloxetine 60 mg / Duloxetine 60-120 mg Duloxetine 30 mg/Duloxetine 60-120 mg Fluoxetine 20 mg/Fluoxetine 20-40 mg Placebo/Duloxetine 60-120 mg Total
Hide Arm/Group Description Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase Participants were treated with Duloxetine 30 mg orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase and Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase Total of all reporting groups
Overall Number of Baseline Participants 108 116 117 122 463
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 108 participants 116 participants 117 participants 122 participants 463 participants
12.92  (2.925) 12.86  (2.904) 13.04  (3.205) 13.09  (2.895) 12.98  (2.977)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 116 participants 117 participants 122 participants 463 participants
Female
60
  55.6%
47
  40.5%
61
  52.1%
69
  56.6%
237
  51.2%
Male
48
  44.4%
69
  59.5%
56
  47.9%
53
  43.4%
226
  48.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participant
Number Analyzed 108 participants 116 participants 117 participants 122 participants 463 participants
American Indian or Alaska Native 15 23 16 19 73
Asian 0 1 1 1 3
Black or African American 27 21 21 24 93
Native Hawaiian or Other Pacific Islander 0 1 0 0 1
White 54 61 67 62 244
Multiracial 6 6 9 13 34
Not Provided 6 3 3 3 15
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 108 participants 116 participants 117 participants 122 participants 463 participants
United States 87 86 93 98 364
Mexico 16 25 16 17 74
Canada 5 5 7 7 24
Argentina 0 0 1 0 1
Children's Depression Rating Scale-Revised (CDRS-R) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 108 participants 116 participants 117 participants 122 participants 463 participants
59.3  (10.87) 59.8  (11.00) 57.9  (10.11) 58.2  (9.35) 58.8  (10.33)
[1]
Measure Description: 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.
CDRS-R Subscale Scores   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 108 participants 116 participants 117 participants 122 participants 463 participants
Mood 16.6  (3.69) 16.4  (3.64) 16.0  (3.52) 16.0  (3.38) 16.2  (3.55)
Somatic 19.6  (4.58) 19.7  (4.87) 19.3  (4.60) 19.5  (4.28) 19.5  (4.57)
Subjective 10.1  (3.51) 10.6  (3.60) 10.0  (3.35) 10.0  (2.79) 10.2  (3.32)
Behavior 13.0  (3.04) 13.1  (3.19) 12.7  (3.12) 12.6  (3.14) 12.8  (3.12)
[1]
Measure Description: CDRS-R Subscale score 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.
Clinical Global Impressions of Severity (CGI-Severity) score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 108 participants 116 participants 117 participants 122 participants 463 participants
4.6  (0.65) 4.6  (0.65) 4.6  (0.59) 4.5  (0.63) 4.6  (0.63)
[1]
Measure Description: CGI-Severity score 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).
1.Primary Outcome
Title Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with both a baseline and at least one post-baseline value.
Arm/Group Title Duloxetine 60mg Placebo
Hide Arm/Group Description:
Duloxetine 60mg orally, once daily for 10 weeks
Placebo capsules identical in appearance, color, taste, and smell to study drug orally, once daily for 10 weeks
Overall Number of Participants Analyzed 105 117
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-23.9  (1.30) -21.6  (1.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine 60mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.193
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint
Time Frame Week 10, Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with value during treatment phase and at least one post-Week 10 value.
Arm/Group Title Duloxetine 60 mg / Duloxetine 60-120 mg Duloxetine 30 mg/Duloxetine 60-120 mg Fluoxetine 20 mg/Fluoxetine 20-40 mg Placebo/Duloxetine 60-120 mg
Hide Arm/Group Description:
Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Duloxetine 30 mg orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase and Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase
Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Overall Number of Participants Analyzed 70 78 80 79
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-7.8  (1.04) -7.4  (1.23) -10.0  (1.17) -9.0  (1.84)
3.Secondary Outcome
Title Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with both a baseline and at least one post-baseline value.
Arm/Group Title Duloxetine 30mg Fluoxetine 20mg Placebo
Hide Arm/Group Description:
Duloxetine 30mg orally, once daily for 10 weeks
Fluoxetine 20mg orally, once daily for 10 weeks
Placebo capsules identical in appearance, color, taste, and smell to study drug orally, once daily for 10 weeks
Overall Number of Participants Analyzed 114 112 117
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-24.6  (1.29) -22.6  (1.27) -21.6  (1.27)
4.Secondary Outcome
Title Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint
Hide Description 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.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with both a baseline and at least one post-baseline values.
Arm/Group Title Duloxetine 60mg Duloxetine 30mg Fluoxetine 20mg Placebo
Hide Arm/Group Description:
Duloxetine 60mg orally, once daily for 10 weeks
Duloxetine 30mg orally, once daily for 10 weeks
Fluoxetine 20mg orally, once daily for 10 weeks
Placebo capsules identical in appearance, color, taste, and smell to study drug orally, once daily for 10 weeks
Overall Number of Participants Analyzed 105 114 112 117
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Mood -7.1  (0.44) -7.2  (0.44) -6.6  (0.43) -6.4  (0.43)
Somatic -7.6  (0.48) -7.9  (0.48) -7.1  (0.47) -6.4  (0.47)
Subjective -3.6  (0.26) -4.0  (0.26) -3.5  (0.26) -3.6  (0.26)
Behavior -5.8  (0.36) -5.6  (0.36) -5.6  (0.35) -5.4  (0.35)
5.Secondary Outcome
Title Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint
Hide Description 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.
Time Frame Week 10, Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with value during treatment phase and at least one post-Week 10 value.
Arm/Group Title Duloxetine 60 mg / Duloxetine 60-120 mg Duloxetine 30 mg/Duloxetine 60-120 mg Fluoxetine 20 mg/Fluoxetine 20-40 mg Placebo/Duloxetine 60-120 mg
Hide Arm/Group Description:
Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Duloxetine 30 mg orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase and Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase
Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Overall Number of Participants Analyzed 70 78 80 79
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Mood -1.9  (0.43) -1.9  (0.42) -2.4  (0.44) -2.3  (0.59)
Somatic -2.8  (0.41) -2.4  (0.52) -4.0  (0.47) -3.2  (0.66)
Subjective -1.2  (0.25) -1.3  (0.19) -1.5  (0.21) -1.0  (0.32)
Behavior -2.1  (0.30) -1.8  (0.32) -2.7  (0.28) -2.4  (0.50)
6.Secondary Outcome
Title Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint
Hide Description 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.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with both a baseline and at least one post-baseline value.
Arm/Group Title Duloxetine 60mg Duloxetine 30mg Fluoxetine 20mg Placebo
Hide Arm/Group Description:
Duloxetine 60mg orally, once daily for 10 weeks
Duloxetine 30mg orally, once daily for 10 weeks
Fluoxetine 20mg orally, once daily for 10 weeks
Placebo capsules identical in appearance, color, taste, and smell to study drug orally, once daily for 10 weeks
Overall Number of Participants Analyzed 105 114 112 117
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.5  (0.12) -1.5  (0.12) -1.4  (0.11) -1.4  (0.11)
7.Secondary Outcome
Title Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint
Hide Description 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.
Time Frame Week 10, Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with value during treatment phase and at least one post-Week 10 value.
Arm/Group Title Duloxetine 60 mg / Duloxetine 60-120 mg Duloxetine 30 mg/Duloxetine 60-120 mg Fluoxetine 20 mg/Fluoxetine 20-40 mg Placebo/Duloxetine 60-120 mg
Hide Arm/Group Description:
Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Duloxetine 30 mg orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase and Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase
Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Overall Number of Participants Analyzed 69 78 81 79
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.1  (0.13) -0.9  (0.16) -1.3  (0.12) -1.0  (0.13)
8.Secondary Outcome
Title Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10
Hide Description 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 to 0).
Time Frame Baseline through Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a baseline and 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.
Arm/Group Title Duloxetine 60mg Duloxetine 30mg Fluoxetine 20mg Placebo
Hide Arm/Group Description:
Duloxetine 60mg orally, once daily for 10 weeks
Duloxetine 30mg orally, once daily for 10 weeks
Fluoxetine 20mg orally, once daily for 10 weeks
Placebo capsules identical in appearance, color, taste, and smell to study drug orally, once daily for 10 weeks
Overall Number of Participants Analyzed 105 115 112 117
Measure Type: Number
Unit of Measure: participants
Suicidal Ideation 16 11 13 15
Suicidal Behavior 0 0 1 1
Treatment Emergent Suicidal Ideation 7 6 9 11
9.Secondary Outcome
Title Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36
Hide Description 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).
Time Frame Week 10 through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a baseline and 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.
Arm/Group Title Duloxetine 60 mg / Duloxetine 60-120 mg Duloxetine 30 mg/Duloxetine 60-120 mg Fluoxetine 20 mg/Fluoxetine 20-40 mg Placebo/Duloxetine 60-120 mg
Hide Arm/Group Description:
Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Duloxetine 30 mg orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase and Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase
Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Overall Number of Participants Analyzed 71 78 80 79
Measure Type: Number
Unit of Measure: participants
Suicidal Ideation 6 12 8 8
Suicidal Behavior 2 3 0 1
Treatment Emergent Suicidal Ideation 5 8 7 6
10.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10
Hide Description 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.
Time Frame Baseline through Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with normal ALT value (ALT<1 x ULN) at last non-missing baseline visit and at least one non-missing post-baseline value.
Arm/Group Title Duloxetine 60mg Duloxetine 30mg Fluoxetine 20mg Placebo
Hide Arm/Group Description:
Duloxetine 60mg orally, once daily for 10 weeks
Duloxetine 30mg orally, once daily for 10 weeks
Fluoxetine 20mg orally, once daily for 10 weeks
Placebo capsules identical in appearance, color, taste, and smell to study drug orally, once daily for 10 weeks
Overall Number of Participants Analyzed 95 98 102 100
Measure Type: Number
Unit of Measure: participants
ALT≥3 x ULN 0 0 0 0
ALT≥5 x ULN 0 0 0 0
ALT≥10 x ULN 0 0 0 0
ALT≥3 x ULN and Total Bilirubin≥2 x ULN 0 0 0 0
11.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36
Hide Description 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 ALT ≥3 x ULN, ALT ≥5 x ULN and ALT ≥10 x ULN, as well as ALT≥3 x ULN and Total Bilirubin ≥2 x ULN.
Time Frame Week 10 through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Duloxetine 60 mg / Duloxetine 60-120 mg Duloxetine 30 mg/Duloxetine 60-120 mg Fluoxetine 20 mg/Fluoxetine 20-40 mg Placebo/Duloxetine 60-120 mg
Hide Arm/Group Description:
Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Duloxetine 30 mg orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase and Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase
Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Overall Number of Participants Analyzed 69 69 77 73
Measure Type: Number
Unit of Measure: participants
ALT≥3 x ULN 0 0 0 0
ALT≥5 x ULN 0 0 0 0
ALT≥10 x ULN 0 0 0 0
ALT≥3 x ULN and Total Bilirubin≥2 x ULN 0 0 0 0
12.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline through Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with normal baseline value and at least one post-baseline value, and who were at risk for the specific PCS criteria.
Arm/Group Title Duloxetine 60mg Duloxetine 30mg Fluoxetine 20mg Placebo
Hide Arm/Group Description:
Duloxetine 60mg orally, once daily for 10 weeks
Duloxetine 30mg orally, once daily for 10 weeks
Fluoxetine 20mg orally, once daily for 10 weeks
Placebo capsules identical in appearance, color, taste, and smell to study drug orally, once daily for 10 weeks
Overall Number of Participants Analyzed 108 116 117 122
Measure Type: Number
Unit of Measure: percentage of participants
Diastolic BP Increase (N=93, 100, 99, 110) 11.8 7.0 10.1 4.5
Systolic BP Increase (N=88, 95, 93, 98) 9.1 12.6 12.9 10.2
Pulse Decrease (N=100, 108, 108, 112) 0 0 0 0
Pulse Increase (N=105, 114, 112, 117) 0 0 0 0
Weight Decrease (N=105, 114, 112, 117) 13.3 8.8 11.6 5.1
13.Secondary Outcome
Title 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
Hide Description PCS increase in systolic and diastolic BP was defined as increase of ≥5 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.
Time Frame Week 10 through Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
Participates with normal value before week 10 and at least one non-missing post-Week 10 value, and who are at risk for the specific PCS criteria.
Arm/Group Title Duloxetine 60 mg / Duloxetine 60-120 mg Duloxetine 30 mg/Duloxetine 60-120 mg Fluoxetine 20 mg/Fluoxetine 20-40 mg Placebo/Duloxetine 60-120 mg
Hide Arm/Group Description:
Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Duloxetine 30 mg orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase and Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase
Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase and Duloxetine 60-120 mg orally, once daily for 6 months during extension phase
Overall Number of Participants Analyzed 73 80 84 82
Measure Type: Number
Unit of Measure: percentage of participants
Diastolic BP Increase (N=55, 65, 64, 69) 14.5 4.6 20.3 11.6
Systolic BP Increase (N=53, 62, 57, 57) 9.4 6.5 7.0 10.5
Pulse Decrease (N=68, 75, 76, 73) 0 0 0 0
Pulse Increase (N=71, 78, 81, 79) 1.4 0 0 1.3
Weight Decrease (N=71, 78, 81, 79) 2.8 9.0 3.7 13.9
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Duloxetine 60 mg - Acute Duloxetine 30 mg - Acute Fluoxetine 20 mg - Acute Placebo - Acute Duloxetine 60 mg - Extension Duloxetine 30 mg - Extension Fluoxetine 20 mg - Extension Placebo/Duloxetine - Extension
Hide Arm/Group Description Duloxetine 60 mg, orally, once daily for 10 weeks Duloxetine 30 mg, orally, once daily for 10 weeks Fluoxetine 20 mg, orally, once daily for 10 weeks Placebo capsules identical in appearance, color, taste, and smell to study drug, orally, once daily for 10 weeks Duloxetine 60-120 mg , orally, once daily for 6 months

Duloxetine 60-120 mg , orally, once daily for 6 months

One participant who had completed the acute treatment phase and didn't go into the extension phase, was accidentally dispensed the drug at the last visit of the acute treatment phase. 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 the number of participants who started the extension phase [see Participant Flow section]).

Fluoxetine 20-40 mg, orally, once daily for 6 months Duloxetine 60-120 mg , orally, once daily for 6 months
All-Cause Mortality
Duloxetine 60 mg - Acute Duloxetine 30 mg - Acute Fluoxetine 20 mg - Acute Placebo - Acute Duloxetine 60 mg - Extension Duloxetine 30 mg - Extension Fluoxetine 20 mg - Extension Placebo/Duloxetine - Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Duloxetine 60 mg - Acute Duloxetine 30 mg - Acute Fluoxetine 20 mg - Acute Placebo - Acute Duloxetine 60 mg - Extension Duloxetine 30 mg - Extension Fluoxetine 20 mg - Extension Placebo/Duloxetine - Extension
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/108 (3.70%)      2/116 (1.72%)      6/117 (5.13%)      2/122 (1.64%)      3/73 (4.11%)      2/81 (2.47%)      1/84 (1.19%)      4/82 (4.88%)    
Gastrointestinal disorders                 
Irritable bowel syndrome  1  1/108 (0.93%)  1 0/116 (0.00%)  0 0/117 (0.00%)  0 0/122 (0.00%)  0 1/73 (1.37%)  1 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Infections and infestations                 
Tuberculosis of peripheral lymph nodes  1  0/108 (0.00%)  0 0/116 (0.00%)  0 1/117 (0.85%)  1 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Injury, poisoning and procedural complications                 
Intentional overdose  1  2/108 (1.85%)  2 0/116 (0.00%)  0 1/117 (0.85%)  1 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 1/82 (1.22%)  1
Road traffic accident  1  0/108 (0.00%)  0 0/116 (0.00%)  0 0/117 (0.00%)  0 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 1/82 (1.22%)  1
Wound  1  0/108 (0.00%)  0 0/116 (0.00%)  0 0/117 (0.00%)  0 0/122 (0.00%)  0 1/73 (1.37%)  1 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Nervous system disorders                 
Epilepsy  1  0/108 (0.00%)  0 0/116 (0.00%)  0 0/117 (0.00%)  0 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 1/82 (1.22%)  1
Somnolence  1  0/108 (0.00%)  0 0/116 (0.00%)  0 1/117 (0.85%)  1 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 1/84 (1.19%)  1 0/82 (0.00%)  0
Psychiatric disorders                 
Abnormal behaviour  1  0/108 (0.00%)  0 0/116 (0.00%)  0 1/117 (0.85%)  1 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Aggression  1  0/108 (0.00%)  0 0/116 (0.00%)  0 2/117 (1.71%)  2 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Depression  1  0/108 (0.00%)  0 0/116 (0.00%)  0 0/117 (0.00%)  0 0/122 (0.00%)  0 0/73 (0.00%)  0 1/81 (1.23%)  1 0/84 (0.00%)  0 0/82 (0.00%)  0
Depressive symptom  1  0/108 (0.00%)  0 1/116 (0.86%)  1 0/117 (0.00%)  0 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Hallucination  1  0/108 (0.00%)  0 1/116 (0.86%)  1 0/117 (0.00%)  0 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Homicidal ideation  1  0/108 (0.00%)  0 0/116 (0.00%)  0 0/117 (0.00%)  0 1/122 (0.82%)  1 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Self injurious behaviour  1  0/108 (0.00%)  0 1/116 (0.86%)  1 0/117 (0.00%)  0 1/122 (0.82%)  1 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Suicidal ideation  1  1/108 (0.93%)  1 0/116 (0.00%)  0 2/117 (1.71%)  2 0/122 (0.00%)  0 0/73 (0.00%)  0 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Suicide attempt  1  0/108 (0.00%)  0 0/116 (0.00%)  0 0/117 (0.00%)  0 1/122 (0.82%)  1 1/73 (1.37%)  1 2/81 (2.47%)  2 0/84 (0.00%)  0 1/82 (1.22%)  1
Skin and subcutaneous tissue disorders                 
Stevens-Johnson syndrome  1  0/108 (0.00%)  0 0/116 (0.00%)  0 0/117 (0.00%)  0 0/122 (0.00%)  0 1/73 (1.37%)  1 0/81 (0.00%)  0 0/84 (0.00%)  0 0/82 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Duloxetine 60 mg - Acute Duloxetine 30 mg - Acute Fluoxetine 20 mg - Acute Placebo - Acute Duloxetine 60 mg - Extension Duloxetine 30 mg - Extension Fluoxetine 20 mg - Extension Placebo/Duloxetine - Extension
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   76/108 (70.37%)      66/116 (56.90%)      69/117 (58.97%)      71/122 (58.20%)      49/73 (67.12%)      46/81 (56.79%)      45/84 (53.57%)      52/82 (63.41%)    
Gastrointestinal disorders                 
Abdominal pain  1  3/108 (2.78%)  3 2/116 (1.72%)  2 0/117 (0.00%)  0 0/122 (0.00%)  0 4/73 (5.48%)  4 1/81 (1.23%)  1 1/84 (1.19%)  1 0/82 (0.00%)  0
Abdominal pain upper  1  13/108 (12.04%)  14 10/116 (8.62%)  10 10/117 (8.55%)  10 9/122 (7.38%)  12 6/73 (8.22%)  8 6/81 (7.41%)  7 7/84 (8.33%)  7 4/82 (4.88%)  4
Diarrhoea  1  4/108 (3.70%)  4 9/116 (7.76%)  9 3/117 (2.56%)  3 2/122 (1.64%)  3 1/73 (1.37%)  1 5/81 (6.17%)  7 5/84 (5.95%)  5 2/82 (2.44%)  2
Nausea  1  18/108 (16.67%)  20 21/116 (18.10%)  22 11/117 (9.40%)  12 11/122 (9.02%)  11 6/73 (8.22%)  7 13/81 (16.05%)  14 3/84 (3.57%)  5 8/82 (9.76%)  10
Vomiting  1  5/108 (4.63%)  6 7/116 (6.03%)  8 2/117 (1.71%)  2 3/122 (2.46%)  3 4/73 (5.48%)  4 10/81 (12.35%)  13 8/84 (9.52%)  8 8/82 (9.76%)  9
General disorders                 
Fatigue  1  5/108 (4.63%)  5 6/116 (5.17%)  7 4/117 (3.42%)  4 4/122 (3.28%)  4 3/73 (4.11%)  3 2/81 (2.47%)  2 2/84 (2.38%)  2 6/82 (7.32%)  7
Pyrexia  1  1/108 (0.93%)  1 3/116 (2.59%)  4 0/117 (0.00%)  0 4/122 (3.28%)  4 3/73 (4.11%)  3 3/81 (3.70%)  4 1/84 (1.19%)  1 8/82 (9.76%)  8
Infections and infestations                 
Nasopharyngitis  1  3/108 (2.78%)  3 4/116 (3.45%)  4 7/117 (5.98%)  8 3/122 (2.46%)  3 3/73 (4.11%)  3 6/81 (7.41%)  7 7/84 (8.33%)  8 3/82 (3.66%)  3
Upper respiratory tract infection  1  1/108 (0.93%)  1 6/116 (5.17%)  7 3/117 (2.56%)  3 6/122 (4.92%)  6 5/73 (6.85%)  7 4/81 (4.94%)  6 2/84 (2.38%)  2 2/82 (2.44%)  3
Injury, poisoning and procedural complications                 
Incorrect dose administered  1  1/108 (0.93%)  1 1/116 (0.86%)  1 3/117 (2.56%)  3 0/122 (0.00%)  0 5/73 (6.85%)  5 3/81 (3.70%)  3 4/84 (4.76%)  4 1/82 (1.22%)  1
Metabolism and nutrition disorders                 
Decreased appetite  1  6/108 (5.56%)  6 10/116 (8.62%)  10 6/117 (5.13%)  6 4/122 (3.28%)  4 0/73 (0.00%)  0 3/81 (3.70%)  3 1/84 (1.19%)  1 4/82 (4.88%)  4
Nervous system disorders                 
Dizziness  1  9/108 (8.33%)  9 10/116 (8.62%)  11 5/117 (4.27%)  5 8/122 (6.56%)  8 2/73 (2.74%)  2 6/81 (7.41%)  6 2/84 (2.38%)  2 7/82 (8.54%)  7
Headache  1  19/108 (17.59%)  22 20/116 (17.24%)  27 22/117 (18.80%)  26 16/122 (13.11%)  19 6/73 (8.22%)  8 4/81 (4.94%)  4 10/84 (11.90%)  14 11/82 (13.41%)  13
Somnolence  1  11/108 (10.19%)  11 3/116 (2.59%)  3 4/117 (3.42%)  4 6/122 (4.92%)  6 1/73 (1.37%)  1 0/81 (0.00%)  0 0/84 (0.00%)  0 2/82 (2.44%)  2
Respiratory, thoracic and mediastinal disorders                 
Cough  1  2/108 (1.85%)  2 4/116 (3.45%)  4 2/117 (1.71%)  2 3/122 (2.46%)  3 2/73 (2.74%)  2 1/81 (1.23%)  1 5/84 (5.95%)  5 3/82 (3.66%)  3
Oropharyngeal pain  1  3/108 (2.78%)  3 2/116 (1.72%)  2 6/117 (5.13%)  6 3/122 (2.46%)  3 3/73 (4.11%)  4 1/81 (1.23%)  1 0/84 (0.00%)  0 2/82 (2.44%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00849693     History of Changes
Obsolete Identifiers: NCT00892294
Other Study ID Numbers: 7109
F1J-MC-HMCL ( Other Identifier: Eli Lilly and Company )
First Submitted: February 23, 2009
First Posted: February 24, 2009
Results First Submitted: February 22, 2012
Results First Posted: April 19, 2012
Last Update Posted: April 19, 2012