Major Depressive Disorder
Conditions
Brief summary
The purpose of this study is to assess whether duloxetine is superior to placebo in the treatment of children and adolescents with major depressive disorder (MDD)
Interventions
DRUGPlacebo
Capsules identical in appearance, color, taste, and smell to study drug, orally, once daily for 10 weeks (acute treatment phase)
DRUGfluoxetine
20 milligram (mg) orally, once daily for 10 weeks (acute treatment phase) and 20-40 mg orally, once daily for additional 6 months (extension phase)
DRUGduloxetine
60 mg orally, once daily for 10 weeks (acute treatment phase) and 60-120 mg orally, once daily for additional 6 months (extension phase)
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Outpatient, diagnosed with major depressive disorder (MDD) as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and supported by the Mini International Neuropsychiatric Interview for children and adolescents (MINI-KID). * Diagnosis of moderate or greater severity of MDD as determined by Children's Depression Rating Scale - Revised (CDRS-R) with a total score greater than or equal to 40 at screen, and randomization and a Clinical Global Impression of Severity (CGI-Severity) rating of greater than or equal to 4 at screen, and randomization. * Female patients must test negative for pregnancy during screening. * Judged to be reliable by the investigator to keep all appointments for clinical visits, tests, and procedures required by the protocol. * Has a degree of understanding such that they can communicate intelligently with the investigator and study coordinator. * Capable of swallowing study drug whole. It is anticipated the patients will need to swallow up to 6 capsules per day. * Patients must have venous access sufficient to allow blood sampling and are compliant with blood draws as per the protocol.
Exclusion criteria
* Children of site personnel directly affiliated with this study and/or their immediate families. * Children of Lilly employees or employees of the designated clinical research organization (CRO) assisting with the conduct of the study. * Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. * Have a current or previous diagnosis of bipolar disorder, psychotic depression, schizophrenia or other psychotic disorder, anorexia, bulimia, obsessive compulsive disorder, or pervasive development disorder, as judged by the investigator. * Have a history of DSM-IV-TR-defined substance abuse or dependence within the past year, excluding caffeine and nicotine. * Have a current primary DSM-IV-TR Axis I disorder other than MDD or a current secondary DSM-IV-TR Axis I disorder that requires any pharmacologic treatment * Have 1 or more first-degree relatives with diagnosed bipolar I disorder. * Have a significant suicide attempt within 1 year of screening or are currently at risk of suicide in the opinion of the investigator. * Have a weight less than 20 kilogram (kg) at screening. * Have a lack of response to 2 or more adequate treatment trials of antidepressants at a clinically appropriate dose for a minimum of 4 weeks for the same MDD episode. * Have initiated, stopped, or changed the type or intensity of psychotherapy within 6 weeks prior to screening. * Have a history of seizure disorder (other than febrile seizures). * Have a history of electroconvulsive therapy within 1 year of screening. * Have had treatment with a monoamine oxidase inhibitor (MAOI) within 14 days or fluoxetine within 30 days of randomization; or the potential need to use an MAOI during the study or within 5 weeks of discontinuation of study drug. * Have previously enrolled, completed, or withdrawn from this study or any other study investigating duloxetine or fluoxetine. * Have a positive urine drug screen for any substances of abuse or excluded medication. * Are taking any excluded medications that cannot be discontinued by screening. * Have known hypersensitivity to duloxetine, fluoxetine, or their inactive ingredients; or have frequent or severe allergic reactions to multiple medications. * Have uncontrolled narrow-angle glaucoma. * Have acute liver injury or severe cirrhosis. * Have a serious or unstable medical illness, psychological condition, or clinically significant laboratory or electrocardiogram (ECG) result that, in the opinion of the investigator, would compromise participation in the study or be likely to lead to hospitalization. * Have abnormal thyroid-stimulating hormone concentration. * Have initiated or discontinued hormone therapy within the previous 3 months. * Female patients who are either pregnant, nursing or have recently given birth. * Need to use thioridazine during the study or within 5 weeks after discontinuation of study drug or need to use pimozide during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint | Baseline, Week 10 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint | Baseline, Week 10 | 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. |
| Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Baseline, Week 10 | 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. |
| Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Week 10, Week 36 | 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. |
| Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint | Baseline, Week 10 | 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. |
| Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint | Week 10, Week 36 | 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. |
| Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint | Week 10, Week 36 | 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. |
| Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Week 10 through Week 36 | 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). |
| Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | Baseline through Week 10 | 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. |
| Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | Week 10 through Week 36 | 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. |
| 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 | Baseline through Week 10 | 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. |
| 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 | Week 10 through Week 36 | 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. |
| Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Baseline through Week 10 | 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). |
Countries
Argentina, Canada, Mexico, United States
Participant flow
Pre-assignment details
This study consisted of a 10-week acute treatment phase, and a 6-month extension phase.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine 60 mg / Duloxetine 60-120 mg 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 | 108 |
| Duloxetine 30 mg/Duloxetine 60-120 mg 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 | 116 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg 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 | 117 |
| Placebo/Duloxetine 60-120 mg 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 | 122 |
| Total | 463 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Acute Treatment Phase | Adverse Event | 12 | 7 | 6 | 4 |
| Acute Treatment Phase | Lack of Efficacy | 1 | 3 | 1 | 2 |
| Acute Treatment Phase | Lost to Follow-up | 5 | 8 | 11 | 9 |
| Acute Treatment Phase | Parent or caregiver decision | 7 | 6 | 7 | 7 |
| Acute Treatment Phase | Physician Decision | 2 | 1 | 2 | 1 |
| Acute Treatment Phase | Protocol Violation | 1 | 5 | 2 | 6 |
| Acute Treatment Phase | Sponsor decision | 0 | 0 | 1 | 0 |
| Acute Treatment Phase | Withdrawal by Subject | 5 | 5 | 3 | 8 |
| Extension Phase | Adverse Event | 4 | 6 | 3 | 7 |
| Extension Phase | Lack of Efficacy | 2 | 2 | 2 | 1 |
| Extension Phase | Lost to Follow-up | 7 | 5 | 6 | 6 |
| Extension Phase | Parent or caregiver decision | 9 | 4 | 10 | 5 |
| Extension Phase | Physician Decision | 1 | 1 | 2 | 0 |
| Extension Phase | Protocol Violation | 0 | 3 | 2 | 3 |
| Extension Phase | Sponsor decision | 1 | 0 | 0 | 1 |
| Extension Phase | Withdrawal by Subject | 6 | 9 | 10 | 15 |
Baseline characteristics
| Characteristic | Duloxetine 30 mg/Duloxetine 60-120 mg | Duloxetine 60 mg / Duloxetine 60-120 mg | Total | Placebo/Duloxetine 60-120 mg | Fluoxetine 20 mg/Fluoxetine 20-40 mg |
|---|---|---|---|---|---|
| Age Continuous | 12.86 years STANDARD_DEVIATION 2.904 | 12.92 years STANDARD_DEVIATION 2.925 | 12.98 years STANDARD_DEVIATION 2.977 | 13.09 years STANDARD_DEVIATION 2.895 | 13.04 years STANDARD_DEVIATION 3.205 |
| CDRS-R Subscale Scores Behavior | 13.1 units on a scale STANDARD_DEVIATION 3.19 | 13.0 units on a scale STANDARD_DEVIATION 3.04 | 12.8 units on a scale STANDARD_DEVIATION 3.12 | 12.6 units on a scale STANDARD_DEVIATION 3.14 | 12.7 units on a scale STANDARD_DEVIATION 3.12 |
| CDRS-R Subscale Scores Mood | 16.4 units on a scale STANDARD_DEVIATION 3.64 | 16.6 units on a scale STANDARD_DEVIATION 3.69 | 16.2 units on a scale STANDARD_DEVIATION 3.55 | 16.0 units on a scale STANDARD_DEVIATION 3.38 | 16.0 units on a scale STANDARD_DEVIATION 3.52 |
| CDRS-R Subscale Scores Somatic | 19.7 units on a scale STANDARD_DEVIATION 4.87 | 19.6 units on a scale STANDARD_DEVIATION 4.58 | 19.5 units on a scale STANDARD_DEVIATION 4.57 | 19.5 units on a scale STANDARD_DEVIATION 4.28 | 19.3 units on a scale STANDARD_DEVIATION 4.6 |
| CDRS-R Subscale Scores Subjective | 10.6 units on a scale STANDARD_DEVIATION 3.6 | 10.1 units on a scale STANDARD_DEVIATION 3.51 | 10.2 units on a scale STANDARD_DEVIATION 3.32 | 10.0 units on a scale STANDARD_DEVIATION 2.79 | 10.0 units on a scale STANDARD_DEVIATION 3.35 |
| Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 59.8 units on a scale STANDARD_DEVIATION 11 | 59.3 units on a scale STANDARD_DEVIATION 10.87 | 58.8 units on a scale STANDARD_DEVIATION 10.33 | 58.2 units on a scale STANDARD_DEVIATION 9.35 | 57.9 units on a scale STANDARD_DEVIATION 10.11 |
| Clinical Global Impressions of Severity (CGI-Severity) score | 4.6 units on a scale STANDARD_DEVIATION 0.65 | 4.6 units on a scale STANDARD_DEVIATION 0.65 | 4.6 units on a scale STANDARD_DEVIATION 0.63 | 4.5 units on a scale STANDARD_DEVIATION 0.63 | 4.6 units on a scale STANDARD_DEVIATION 0.59 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 23 Participant | 15 Participant | 73 Participant | 19 Participant | 16 Participant |
| Race/Ethnicity, Customized Asian | 1 Participant | 0 Participant | 3 Participant | 1 Participant | 1 Participant |
| Race/Ethnicity, Customized Black or African American | 21 Participant | 27 Participant | 93 Participant | 24 Participant | 21 Participant |
| Race/Ethnicity, Customized Multiracial | 6 Participant | 6 Participant | 34 Participant | 13 Participant | 9 Participant |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participant | 0 Participant | 1 Participant | 0 Participant | 0 Participant |
| Race/Ethnicity, Customized Not Provided | 3 Participant | 6 Participant | 15 Participant | 3 Participant | 3 Participant |
| Race/Ethnicity, Customized White | 61 Participant | 54 Participant | 244 Participant | 62 Participant | 67 Participant |
| Region of Enrollment Argentina | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 5 participants | 5 participants | 24 participants | 7 participants | 7 participants |
| Region of Enrollment Mexico | 25 participants | 16 participants | 74 participants | 17 participants | 16 participants |
| Region of Enrollment United States | 86 participants | 87 participants | 364 participants | 98 participants | 93 participants |
| Sex: Female, Male Female | 47 Participants | 60 Participants | 237 Participants | 69 Participants | 61 Participants |
| Sex: Female, Male Male | 69 Participants | 48 Participants | 226 Participants | 53 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 76 / 108 | 66 / 116 | 69 / 117 | 71 / 122 | 49 / 73 | 46 / 81 | 45 / 84 | 52 / 82 |
| serious Total, serious adverse events | 4 / 108 | 2 / 116 | 6 / 117 | 2 / 122 | 3 / 73 | 2 / 81 | 1 / 84 | 4 / 82 |
Outcome results
Primary
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint
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.
Time frame: Baseline, Week 10
Population: Participants with both a baseline and at least one post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint | -23.9 units on a scale | Standard Error 1.3 |
| Placebo | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint | -21.6 units on a scale | Standard Error 1.27 |
p-value: 0.193Mixed Models Analysis
Secondary
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint
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
Population: Participants with both a baseline and at least one post-baseline values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Mood | -7.1 units on a scale | Standard Error 0.44 |
| Duloxetine 60mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Somatic | -7.6 units on a scale | Standard Error 0.48 |
| Duloxetine 60mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Subjective | -3.6 units on a scale | Standard Error 0.26 |
| Duloxetine 60mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Behavior | -5.8 units on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Somatic | -7.9 units on a scale | Standard Error 0.48 |
| Placebo | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Subjective | -4.0 units on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Behavior | -5.6 units on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Mood | -7.2 units on a scale | Standard Error 0.44 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Subjective | -3.5 units on a scale | Standard Error 0.26 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Somatic | -7.1 units on a scale | Standard Error 0.47 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Behavior | -5.6 units on a scale | Standard Error 0.35 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Mood | -6.6 units on a scale | Standard Error 0.43 |
| Placebo/Duloxetine 60-120 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Behavior | -5.4 units on a scale | Standard Error 0.35 |
| Placebo/Duloxetine 60-120 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Somatic | -6.4 units on a scale | Standard Error 0.47 |
| Placebo/Duloxetine 60-120 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Mood | -6.4 units on a scale | Standard Error 0.43 |
| Placebo/Duloxetine 60-120 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint | Subjective | -3.6 units on a scale | Standard Error 0.26 |
Secondary
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint
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.
Time frame: Baseline, Week 10
Population: Participants with both a baseline and at least one post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint | -24.6 units on a scale | Standard Error 1.29 |
| Placebo | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint | -22.6 units on a scale | Standard Error 1.27 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint | -21.6 units on a scale | Standard Error 1.27 |
Secondary
Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint
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
Population: Participants with both a baseline and at least one post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60mg | Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint | -1.5 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint | -1.5 units on a scale | Standard Error 0.12 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint | -1.4 units on a scale | Standard Error 0.11 |
| Placebo/Duloxetine 60-120 mg | Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint | -1.4 units on a scale | Standard Error 0.11 |
Secondary
Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint
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
Population: Participants with value during treatment phase and at least one post-Week 10 value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Behavior | -2.1 units on a scale | Standard Error 0.3 |
| Duloxetine 60mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Subjective | -1.2 units on a scale | Standard Error 0.25 |
| Duloxetine 60mg | 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 0.43 |
| Duloxetine 60mg | 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 0.41 |
| Placebo | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Somatic | -2.4 units on a scale | Standard Error 0.52 |
| Placebo | 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 0.42 |
| Placebo | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Subjective | -1.3 units on a scale | Standard Error 0.19 |
| Placebo | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Behavior | -1.8 units on a scale | Standard Error 0.32 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Subjective | -1.5 units on a scale | Standard Error 0.21 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Behavior | -2.7 units on a scale | Standard Error 0.28 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Somatic | -4.0 units on a scale | Standard Error 0.47 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Mood | -2.4 units on a scale | Standard Error 0.44 |
| Placebo/Duloxetine 60-120 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Behavior | -2.4 units on a scale | Standard Error 0.5 |
| Placebo/Duloxetine 60-120 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Mood | -2.3 units on a scale | Standard Error 0.59 |
| Placebo/Duloxetine 60-120 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Somatic | -3.2 units on a scale | Standard Error 0.66 |
| Placebo/Duloxetine 60-120 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint | Subjective | -1.0 units on a scale | Standard Error 0.32 |
Secondary
Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint
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.
Time frame: Week 10, Week 36
Population: Participants with value during treatment phase and at least one post-Week 10 value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint | -7.8 units on a scale | Standard Error 1.04 |
| Placebo | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint | -7.4 units on a scale | Standard Error 1.23 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint | -10.0 units on a scale | Standard Error 1.17 |
| Placebo/Duloxetine 60-120 mg | Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint | -9.0 units on a scale | Standard Error 1.84 |
Secondary
Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint
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
Population: Participants with value during treatment phase and at least one post-Week 10 value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60mg | Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint | -1.1 units on a scale | Standard Error 0.13 |
| Placebo | Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint | -0.9 units on a scale | Standard Error 0.16 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint | -1.3 units on a scale | Standard Error 0.12 |
| Placebo/Duloxetine 60-120 mg | Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint | -1.0 units on a scale | Standard Error 0.13 |
Secondary
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine 60mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥3 x ULN | 0 participants |
| Duloxetine 60mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥5 x ULN | 0 participants |
| Duloxetine 60mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥10 x ULN | 0 participants |
| Duloxetine 60mg | 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 |
| Placebo | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥5 x ULN | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥10 x ULN | 0 participants |
| Placebo | 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 |
| Placebo | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥3 x ULN | 0 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥10 x ULN | 0 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥5 x ULN | 0 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥3 x ULN | 0 participants |
| Placebo/Duloxetine 60-120 mg | 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 |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥5 x ULN | 0 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥3 x ULN | 0 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10 | ALT≥10 x ULN | 0 participants |
Secondary
Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine 60mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥3 x ULN | 0 participants |
| Duloxetine 60mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥5 x ULN | 0 participants |
| Duloxetine 60mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥10 x ULN | 0 participants |
| Duloxetine 60mg | 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 |
| Placebo | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥5 x ULN | 0 participants |
| Placebo | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥10 x ULN | 0 participants |
| Placebo | 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 |
| Placebo | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥3 x ULN | 0 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥10 x ULN | 0 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥5 x ULN | 0 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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 |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥3 x ULN | 0 participants |
| Placebo/Duloxetine 60-120 mg | 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 |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥5 x ULN | 0 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥3 x ULN | 0 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36 | ALT≥10 x ULN | 0 participants |
Secondary
Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine 60mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Treatment Emergent Suicidal Ideation | 7 participants |
| Duloxetine 60mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Suicidal Behavior | 0 participants |
| Duloxetine 60mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Suicidal Ideation | 16 participants |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Treatment Emergent Suicidal Ideation | 6 participants |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Suicidal Behavior | 0 participants |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Suicidal Ideation | 11 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Suicidal Ideation | 13 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Suicidal Behavior | 1 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Treatment Emergent Suicidal Ideation | 9 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Treatment Emergent Suicidal Ideation | 11 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Suicidal Behavior | 1 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10 | Suicidal Ideation | 15 participants |
Secondary
Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine 60mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Suicidal Ideation | 6 participants |
| Duloxetine 60mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Treatment Emergent Suicidal Ideation | 5 participants |
| Duloxetine 60mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Suicidal Behavior | 2 participants |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Suicidal Ideation | 12 participants |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Treatment Emergent Suicidal Ideation | 8 participants |
| Placebo | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Suicidal Behavior | 3 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Suicidal Behavior | 0 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Suicidal Ideation | 8 participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Treatment Emergent Suicidal Ideation | 7 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Suicidal Ideation | 8 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Treatment Emergent Suicidal Ideation | 6 participants |
| Placebo/Duloxetine 60-120 mg | Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36 | Suicidal Behavior | 1 participants |
Secondary
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
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
Population: Participants with normal baseline value and at least one post-baseline value, and who were at risk for the specific PCS criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine 60mg | 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=105, 114, 112, 117) | 0 percentage of participants |
| Duloxetine 60mg | 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=88, 95, 93, 98) | 9.1 percentage of participants |
| Duloxetine 60mg | 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=105, 114, 112, 117) | 13.3 percentage of participants |
| Duloxetine 60mg | 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=100, 108, 108, 112) | 0 percentage of participants |
| Duloxetine 60mg | 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=93, 100, 99, 110) | 11.8 percentage of participants |
| Placebo | 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=100, 108, 108, 112) | 0 percentage of participants |
| Placebo | 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=105, 114, 112, 117) | 0 percentage of participants |
| Placebo | 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=105, 114, 112, 117) | 8.8 percentage of participants |
| Placebo | 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=88, 95, 93, 98) | 12.6 percentage of participants |
| Placebo | 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=93, 100, 99, 110) | 7.0 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=100, 108, 108, 112) | 0 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=93, 100, 99, 110) | 10.1 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=88, 95, 93, 98) | 12.9 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=105, 114, 112, 117) | 0 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=105, 114, 112, 117) | 11.6 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=105, 114, 112, 117) | 0 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=88, 95, 93, 98) | 10.2 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=93, 100, 99, 110) | 4.5 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=100, 108, 108, 112) | 0 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=105, 114, 112, 117) | 5.1 percentage of participants |
Secondary
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
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine 60mg | 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=71, 78, 81, 79) | 1.4 percentage of participants |
| Duloxetine 60mg | 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=53, 62, 57, 57) | 9.4 percentage of participants |
| Duloxetine 60mg | 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=71, 78, 81, 79) | 2.8 percentage of participants |
| Duloxetine 60mg | 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=68, 75, 76, 73) | 0 percentage of participants |
| Duloxetine 60mg | 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=55, 65, 64, 69) | 14.5 percentage of participants |
| Placebo | 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=68, 75, 76, 73) | 0 percentage of participants |
| Placebo | 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=71, 78, 81, 79) | 0 percentage of participants |
| Placebo | 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=71, 78, 81, 79) | 9.0 percentage of participants |
| Placebo | 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=53, 62, 57, 57) | 6.5 percentage of participants |
| Placebo | 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=55, 65, 64, 69) | 4.6 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=68, 75, 76, 73) | 0 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=55, 65, 64, 69) | 20.3 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=53, 62, 57, 57) | 7.0 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=71, 78, 81, 79) | 0 percentage of participants |
| Fluoxetine 20 mg/Fluoxetine 20-40 mg | 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=71, 78, 81, 79) | 3.7 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=71, 78, 81, 79) | 1.3 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=53, 62, 57, 57) | 10.5 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=55, 65, 64, 69) | 11.6 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=68, 75, 76, 73) | 0 percentage of participants |
| Placebo/Duloxetine 60-120 mg | 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=71, 78, 81, 79) | 13.9 percentage of participants |