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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00849901
• Collaborator: (none)
• Enrollment: 337
• Locations: 59
• Arms: 3
• Duration (Months): 31
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: duloxetine; Drug: Placebo; Drug: fluoxetine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 337 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Efficacy and Safety Study of Duloxetine Versus Placebo in the Treatment of Children and Adolescents With Major Depressive Disorder
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Capsules identical in appearance, color, taste and smell to study drug, orally (PO), once daily (QD). Dose: placebo, 6 capsules, QD for 10 weeks
Active Comparator: Fluoxetine	Drug: fluoxetine; 10-40 milligram (mg), PO, QD, for up to 38 weeks; Other Names: LY110140 Prozac
Experimental: Duloxetine	Drug: duloxetine; 30-120 mg, PO, QD, for up to 38 weeks; Other Names: LY248686 Cymbalta

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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 - 0).

7. 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).

8. 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.

9. 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 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.

10. 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.

11. 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 ≥ 5mm Hg from baseline (BL) high value to a value above the 95th percentile at post-BL; PCS increase of pulse was defined as >140 and increase of ≥15 from BL high value for age 7-11 and >120 and increase of ≥15 from BL high value for age 12-17; PCS decrease of pulse was defined as <60 and a decrease of ≥25 from BL low value for age 7-11 and <50 and a decrease of ≥15 from BL low value for age 12-17; PCS decrease of weight was defined as decrease of at least 3.5% from BL low value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Costa Mesa	California	United States	92626
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Irvine	California	United States	92612
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Palo Alto	California	United States	94306
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Altamonte Springs	Florida	United States	32701
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Lauderdale	Florida	United States	33319
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Marietta	Georgia	United States	30060
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Smyrna	Georgia	United States	30080
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Coeur d'Alene	Idaho	United States	83814
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Libertyville	Illinois	United States	60048
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rochester Hills	Michigan	United States	48307
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Charles	Missouri	United States	63301
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Omaha	Nebraska	United States	68105
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Las Vegas	Nevada	United States	89128
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Willingboro	New Jersey	United States	08046
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rochester	New York	United States	14618
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Staten Island	New York	United States	10312
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wilmington	North Carolina	United States	28401
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Beachwood	Ohio	United States	44122
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Middleburg Heights	Ohio	United States	44130
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bartlett	Tennessee	United States	38134
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Houston	Texas	United States	77090
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Antonio	Texas	United States	78229
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Clinton	Utah	United States	84015
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Orem	Utah	United States	84058
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Elancourt		France	78990
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Paris		France	75019
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rouffach		France	68250
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Koeln		Germany	50931
29	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mannheim		Germany	68159
30	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tubingen		Germany	72076
31	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ulm		Germany	89075
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kazan		Russian Federation	420012
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Moscow		Russian Federation	107076
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nizhniy Novgorod		Russian Federation	603155
35	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Novosibirsk		Russian Federation	1630064
36	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rostov-On-Don		Russian Federation	344010
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Petersburg		Russian Federation	192019
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saratov		Russian Federation	410028
39	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Smolensk		Russian Federation	214019
40	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Stavropol		Russian Federation	355000
41	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tomsk		Russian Federation	634014
42	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kosice		Slovakia	041 90
43	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Martin		Slovakia	03659
44	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bloemfontein		South Africa	9301
45	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cape Town		South Africa	7530
46	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Centurion		South Africa	0046
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Johannesburg		South Africa	2191
48	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pretoria		South Africa	0042
49	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Vereeniging		South Africa	1939
50	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	West Cape		South Africa	7500
51	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Donetsk		Ukraine	83037
52	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kharkiv		Ukraine	61153
53	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kyiv		Ukraine	04080
54	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lugansk		Ukraine	91045
55	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Odesa		Ukraine	65006
56	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Poltava		Ukraine	36006
57	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ternopil		Ukraine	46000
58	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Uzhorod		Ukraine	88000
59	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Vinnytsya		Ukraine	21005

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00849901
• Other Study ID Numbers: 6223; F1J-MC-HMCK
• First Posted: Feb 24, 2009
• Last Update Posted: Sep 11, 2017
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Duloxetine Hydrochloride; Fluoxetine

Study Results

Participant Flow

Pre-assignment Detail	This study consisted of a 10-week acute treatment phase, and a 6-month extension phase.

Arm/Group Title	Duloxetine/Duloxetine	Fluoxetine/Fluoxetine	Placebo/Duloxetine
Arm/Group Description	Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase	Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase	Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
Period Title: Acute Treatment Phase
STARTED	117	117	103
COMPLETED	87	91	87
NOT COMPLETED	30	26	16
Period Title: Acute Treatment Phase
STARTED	83	91	86
COMPLETED	56	65	69
NOT COMPLETED	27	26	17

Baseline Characteristics

Arm/Group Title	Duloxetine/Duloxetine	Fluoxetine/Fluoxetine	Placebo/Duloxetine	Total
Arm/Group Description	Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase	Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase	Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase	Total of all reporting groups
Overall Participants	117	117	103	337
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.14 (3.043)	13.08 (3.272)	13.28 (3.055)	13.16 (3.120)
Sex: Female, Male (Count of Participants)
Female	64 54.7%	61 52.1%	51 49.5%	176 52.2%
Male	53 45.3%	56 47.9%	52 50.5%	161 47.8%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	1 0.9%	1 0.9%	1 1%	3 0.9%
Asian	0 0%	2 1.7%	0 0%	2 0.6%
Black or African American	17 14.5%	9 7.7%	13 12.6%	39 11.6%
White	90 76.9%	93 79.5%	79 76.7%	262 77.7%
Multiracial	4 3.4%	7 6%	5 4.9%	16 4.7%
Not Provided	5 4.3%	5 4.3%	5 4.9%	15 4.5%
Region of Enrollment (participants) [Number]
United States	50 42.7%	45 38.5%	45 43.7%	140 41.5%
Finland	1 0.9%	4 3.4%	0 0%	5 1.5%
France	3 2.6%	2 1.7%	3 2.9%	8 2.4%
Germany	1 0.9%	1 0.9%	2 1.9%	4 1.2%
Slovakia	2 1.7%	3 2.6%	1 1%	6 1.8%
Ukraine	25 21.4%	23 19.7%	18 17.5%	66 19.6%
Russian Federation	13 11.1%	15 12.8%	12 11.7%	40 11.9%
Estonia	1 0.9%	0 0%	0 0%	1 0.3%
South Africa	21 17.9%	24 20.5%	22 21.4%	67 19.9%
Children's Depression Rating Scale-Revised (CDRS-R) Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	59.2 (10.45)	58.8 (10.56)	60.2 (11.67)	59.4 (10.85)
CDRS-R Subscale Scores (units on a scale) [Mean (Standard Deviation) ]
Mood	16.3 (3.54)	15.9 (3.85)	16.1 (3.59)	16.1 (3.66)
Somatic	19.8 (4.54)	19.7 (4.21)	20.0 (4.75)	19.8 (4.48)
Subjective	10.1 (3.08)	10.4 (3.24)	10.4 (3.46)	10.3 (3.25)
Behavior	13.0 (2.79)	12.8 (2.87)	13.5 (3.00)	13.1 (2.89)
Clinical Global Impressions of Severity (CGI-Severity) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.5 (0.62)	4.5 (0.58)	4.6 (0.65)	4.5 (0.62)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint
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. 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

Outcome Measure Data

Analysis Population Description

Participants with both a baseline and at least one post-baseline value.

Arm/Group Title	Duloxetine	Fluoxetine	Placebo
Arm/Group Description	Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase	Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase	Received placebo PO, QD during acute treatment phase
Measure Participants	113	113	103
Least Squares Mean (Standard Error) [units on a scale]	-24.3 (1.09)	-23.7 (1.06)	-24.3 (1.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint
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. LS means are adjusted for baseline, pooled investigator, age category, visit, age category*visit and baseline*visit.
Time Frame	Week 10, Week 36

Outcome Measure Data

Analysis Population Description

Participants with value during treatment phase and at least one post-Week 10 value.

Arm/Group Title	Duloxetine/Duloxetine	Fluoxetine/Fluoxetine	Placebo/Duloxetine
Arm/Group Description	Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase	Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase	Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
Measure Participants	81	91	85
Least Squares Mean (Standard Deviation) [units on a scale]	-7.2 (0.86)	-9.9 (0.72)	-9.6 (0.86)

3. Secondary Outcome

Title	Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint
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

Outcome Measure Data

Analysis Population Description

Participants with both a baseline and at least one post-baseline value.

Arm/Group Title	Duloxetine	Fluoxetine	Placebo
Arm/Group Description	Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase	Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase	Received placebo PO, QD during acute treatment phase
Measure Participants	113	113	103
Mood (N=113, 113, 103)	-7.0 (0.36)	-7.1 (0.35)	-7.0 (0.37)
Somatic (N=113, 113, 103)	-7.7 (0.42)	-7.6 (0.41)	-7.7 (0.42)
Subjective (N=113, 113, 103)	-4.0 (0.23)	-3.6 (0.22)	-4.0 (0.23)
Behavior (N=113, 112, 103)	-5.6 (0.30)	-5.4 (0.30)	-5.7 (0.31)

4. Secondary Outcome

Title	Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint
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

Outcome Measure Data

Analysis Population Description

Participants with value during treatment phase and at least one post-Week 10 value.

Arm/Group Title	Duloxetine/Duloxetine	Fluoxetine/Fluoxetine	Placebo/Duloxetine
Arm/Group Description	Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase	Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase	Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
Measure Participants	81	91	85
Mood	-1.9 (0.34)	-2.5 (0.24)	-2.9 (0.29)
Somatic	-2.8 (0.35)	-3.6 (0.27)	-3.2 (0.33)
Subjective	-0.3 (0.24)	-1.3 (0.13)	-1.2 (0.17)
Behavior	-1.9 (0.23)	-2.8 (0.20)	-2.1 (0.36)

5. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint
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

Outcome Measure Data

Analysis Population Description

Participants with both a baseline and at least one post-baseline value.

Arm/Group Title	Duloxetine	Fluoxetine	Placebo
Arm/Group Description	Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase	Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase	Received placebo PO, QD during acute treatment phase
Measure Participants	113	113	110
Least Squares Mean (Standard Error) [units on a scale]	-1.9 (0.11)	-1.8 (0.10)	-1.9 (0.11)

6. Secondary Outcome

Title	Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint
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

Outcome Measure Data

Analysis Population Description

Participants with value during treatment phase and at least one post-Week 10 value.

Arm/Group Title	Duloxetine/Duloxetine	Fluoxetine/Fluoxetine	Placebo/Duloxetine
Arm/Group Description	Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase	Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase	Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
Measure Participants	81	91	85
Least Squares Mean (Standard Error) [units on a scale]	-0.6 (0.12)	-1.0 (0.07)	-1.1 (0.10)

7. Secondary Outcome

Title	Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10
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 - 0).
Time Frame	Baseline through Week 10

Outcome Measure Data

Analysis Population Description

Participants with at least one post-baseline C-SSRS suicidal ideation or suicidal behavior score and who are at risk for treatment emergent suicidal ideation or behavior.

Arm/Group Title	Duloxetine	Fluoxetine	Placebo
Arm/Group Description	Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase	Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase	Received placebo PO, QD during acute treatment phase
Measure Participants	113	113	103
Suicidal Ideation	16 13.7%	16 13.7%	15 14.6%
Suicidal Behavior	0 0%	1 0.9%	0 0%
Treatment Emergent Suicidal Ideation	8 6.8%	9 7.7%	7 6.8%

8. Secondary Outcome

Title	Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36
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

Outcome Measure Data

Analysis Population Description

Participants with at least one post-baseline C-SSRS suicidal ideation or suicidal behavior score and who are at risk for treatment emergent suicidal ideation or behavior.

Arm/Group Title	Duloxetine/Duloxetine	Fluoxetine/Fluoxetine	Placebo/Duloxetine
Arm/Group Description	Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase	Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase	Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
Measure Participants	81	91	85
Suicidal Ideation	13 11.1%	13 11.1%	8 7.8%
Suicidal Behavior	1 0.9%	1 0.9%	0 0%
Treatment Emergent Suicidal Ideation	9 7.7%	13 11.1%	8 7.8%

9. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10
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

Outcome Measure Data

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	Fluoxetine	Placebo
Arm/Group Description	Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase	Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase	Received placebo PO, QD during acute treatment phase
Measure Participants	101	102	94
ALT≥3 x ULN	0 0%	0 0%	0 0%
ALT≥5 x ULN	0 0%	0 0%	0 0%
ALT≥10 x ULN	0 0%	0 0%	0 0%
ALT≥3 x ULN and Total Bilirubin≥2 x ULN	0 0%	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36
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	Week 10 through Week 36

Outcome Measure Data

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/Duloxetine	Fluoxetine/Fluoxetine	Placebo/Duloxetine
Arm/Group Description	Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase	Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase	Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
Measure Participants	77	83	82
ALT≥3 x ULN	0 0%	1 0.9%	0 0%
ALT≥5 x ULN	0 0%	1 0.9%	0 0%
ALT≥10 x ULN	0 0%	0 0%	0 0%
ALT≥3 x ULN and Total Bilirubin≥2 x ULN	0 0%	0 0%	0 0%

11. 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
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

Outcome Measure Data

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	Fluoxetine	Placebo
Arm/Group Description	Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase	Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase	Received placebo PO, QD during acute treatment phase
Measure Participants	117	117	103
Diastolic BP Increase (N=102, 106, 93)	8.8 7.5%	7.5 6.4%	17.2 16.7%
Systolic BP Increase (N=100, 106, 90)	7.0 6%	5.7 4.9%	6.7 6.5%
Pulse Decrease (N=111, 112, 102)	0.9 0.8%	0.9 0.8%	1.0 1%
Pulse Increase (N=113, 114, 103)	0 0%	0 0%	1.0 1%
Weight Decrease (N=113, 114, 103)	12.4 10.6%	11.4 9.7%	4.9 4.8%

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 Week 10 Through Week 36
Description	PCS increase in systolic and diastolic BP was defined as increase of ≥ 5mm Hg from baseline (BL) high value to a value above the 95th percentile at post-BL; PCS increase of pulse was defined as >140 and increase of ≥15 from BL high value for age 7-11 and >120 and increase of ≥15 from BL high value for age 12-17; PCS decrease of pulse was defined as <60 and a decrease of ≥25 from BL low value for age 7-11 and <50 and a decrease of ≥15 from BL low value for age 12-17; PCS decrease of weight was defined as decrease of at least 3.5% from BL low value.
Time Frame	Week 10 through Week 36

Outcome Measure Data

Analysis Population Description

Participants with normal value at last non-missing visit before Week 10 and at least one non-missing post-Week 10 value, and who are at risk for the specific PCS criteria.

Arm/Group Title	Duloxetine/Duloxetine	Fluoxetine/Fluoxetine	Placebo/Duloxetine
Arm/Group Description	Received duloxetine 60, 90, and/or 120 milligram (mg) orally (PO), once daily (QD) during both acute treatment phase and extension phase	Received fluoxetine 20 and/or 40 mg PO, QD during both acute treatment phase and extension phase	Received placebo PO, QD during acute treatment phase, and duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
Measure Participants	83	91	86
Diastolic BP Increase (N=65, 76, 61)	16.9 14.4%	11.8 10.1%	4.9 4.8%
Systolic BP Increase (N=64, 80, 69)	12.5 10.7%	12.5 10.7%	10.1 9.8%
Pulse Decrease (N=78, 84, 82)	0 0%	0 0%	0 0%
Pulse Increase (N=81, 91, 84)	0 0%	0 0%	0 0%
Weight Decrease (N=81, 91, 85)	6.2 5.3%	3.3 2.8%	9.4 9.1%

Adverse Events

Arm/Group Title	Duloxetine - Acute		Fluoxetine - Acute		Placebo - Acute		Duloxetine - Extension		Fluoxetine - Extension		Placebo/Duloxetine - Extension
Arm/Group Description	Received duloxetine 60, 90, and/or 120 mg orally (PO), once daily (QD) during acute treatment phase		Received fluoxetine 20 and/or 40 mg PO, QD during acute treatment phase		Received placebo PO, QD during acute treatment phase		Received duloxetine 60, 90, and/or 120 mg PO, QD during extension phase		Received fluoxetine 20 and/or 40 mg PO, QD during extension phase. One participant had discontinued the acute phase due to an adverse event but was accidentally dispensed drug at the last visit of the acute phase, thus based on intent-to-treat principal, this participant was included in the extension phase analyses for adverse events (AEs) (resulting in one more participant being analyzed for AEs than started the extension phase in the Participant Flow section).		Received duloxetine 60, 90, and/or 120 mg PO, QD during extension phase
All Cause Mortality
	Duloxetine - Acute		Fluoxetine - Acute		Placebo - Acute		Duloxetine - Extension		Fluoxetine - 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
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Duloxetine - Acute		Fluoxetine - Acute		Placebo - Acute		Duloxetine - Extension		Fluoxetine - 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
Total	3/117 (2.6%)		2/117 (1.7%)		1/103 (1%)		1/83 (1.2%)		4/92 (4.3%)		4/86 (4.7%)
Blood and lymphatic system disorders
Lymphadenitis	0/117 (0%)	0	1/117 (0.9%)	1	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	0/86 (0%)	0
Gastrointestinal disorders
Gastritis	0/117 (0%)	0	1/117 (0.9%)	1	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	0/86 (0%)	0
Infections and infestations
Pilonidal cyst	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	1/86 (1.2%)	1
Pneumonia	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	1/83 (1.2%)	1	0/92 (0%)	0	0/86 (0%)	0
Injury, poisoning and procedural complications
Intentional overdose	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	1/92 (1.1%)	1	0/86 (0%)	0
Ulna fracture	0/117 (0%)	0	1/117 (0.9%)	1	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	0/86 (0%)	0
Nervous system disorders
Convulsion	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	1/92 (1.1%)	1	0/86 (0%)	0
Epilepsy	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	1/92 (1.1%)	1	0/86 (0%)	0
Syncope	1/117 (0.9%)	1	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	0/86 (0%)	0
Psychiatric disorders
Adjustment disorder with disturbance of conduct	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	1/92 (1.1%)	1	0/86 (0%)	0
Conversion disorder	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	1/86 (1.2%)	1
Drug abuse	1/117 (0.9%)	1	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	0/86 (0%)	0
Hypomania	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	1/92 (1.1%)	1	0/86 (0%)	0
Major depression	0/117 (0%)	0	0/117 (0%)	0	1/103 (1%)	1	0/83 (0%)	0	0/92 (0%)	0	1/86 (1.2%)	1
Panic attack	1/117 (0.9%)	1	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	0/86 (0%)	0
Restlessness	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	1/86 (1.2%)	1
Social phobia	1/117 (0.9%)	1	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	0/86 (0%)	0
Suicidal ideation	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	0/92 (0%)	0	1/86 (1.2%)	1
Suicide attempt	0/117 (0%)	0	0/117 (0%)	0	0/103 (0%)	0	0/83 (0%)	0	1/92 (1.1%)	1	0/86 (0%)	0
Other (Not Including Serious) Adverse Events
	Duloxetine - Acute		Fluoxetine - Acute		Placebo - Acute		Duloxetine - Extension		Fluoxetine - 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
Total	70/117 (59.8%)		72/117 (61.5%)		68/103 (66%)		53/83 (63.9%)		56/92 (60.9%)		60/86 (69.8%)
Gastrointestinal disorders
Abdominal pain	1/117 (0.9%)	1	2/117 (1.7%)	2	5/103 (4.9%)	5	1/83 (1.2%)	1	2/92 (2.2%)	2	1/86 (1.2%)	1
Abdominal pain upper	4/117 (3.4%)	4	5/117 (4.3%)	7	7/103 (6.8%)	8	1/83 (1.2%)	1	2/92 (2.2%)	2	7/86 (8.1%)	7
Diarrhoea	6/117 (5.1%)	6	2/117 (1.7%)	2	2/103 (1.9%)	2	3/83 (3.6%)	3	4/92 (4.3%)	4	2/86 (2.3%)	2
Nausea	20/117 (17.1%)	28	15/117 (12.8%)	17	11/103 (10.7%)	14	3/83 (3.6%)	6	7/92 (7.6%)	8	12/86 (14%)	17
Vomiting	7/117 (6%)	7	6/117 (5.1%)	7	3/103 (2.9%)	3	4/83 (4.8%)	5	5/92 (5.4%)	5	8/86 (9.3%)	9
General disorders
Fatigue	8/117 (6.8%)	8	3/117 (2.6%)	5	5/103 (4.9%)	5	1/83 (1.2%)	1	3/92 (3.3%)	3	4/86 (4.7%)	4
Infections and infestations
Gastroenteritis	0/117 (0%)	0	1/117 (0.9%)	1	2/103 (1.9%)	2	4/83 (4.8%)	4	2/92 (2.2%)	2	3/86 (3.5%)	3
Influenza	7/117 (6%)	7	3/117 (2.6%)	3	6/103 (5.8%)	8	5/83 (6%)	6	3/92 (3.3%)	3	4/86 (4.7%)	4
Nasopharyngitis	2/117 (1.7%)	2	4/117 (3.4%)	4	5/103 (4.9%)	5	9/83 (10.8%)	9	8/92 (8.7%)	12	9/86 (10.5%)	9
Sinusitis	1/117 (0.9%)	1	1/117 (0.9%)	1	3/103 (2.9%)	3	4/83 (4.8%)	4	1/92 (1.1%)	1	1/86 (1.2%)	1
Upper respiratory tract infection	4/117 (3.4%)	4	3/117 (2.6%)	3	1/103 (1%)	1	5/83 (6%)	6	5/92 (5.4%)	7	3/86 (3.5%)	3
Injury, poisoning and procedural complications
Incorrect dose administered	2/117 (1.7%)	2	4/117 (3.4%)	5	3/103 (2.9%)	3	4/83 (4.8%)	5	3/92 (3.3%)	3	0/86 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	10/117 (8.5%)	11	10/117 (8.5%)	10	7/103 (6.8%)	7	2/83 (2.4%)	3	0/92 (0%)	0	3/86 (3.5%)	3
Nervous system disorders
Dizziness	10/117 (8.5%)	11	4/117 (3.4%)	4	3/103 (2.9%)	3	3/83 (3.6%)	3	3/92 (3.3%)	3	6/86 (7%)	6
Headache	19/117 (16.2%)	23	18/117 (15.4%)	22	9/103 (8.7%)	10	9/83 (10.8%)	10	9/92 (9.8%)	10	10/86 (11.6%)	12
Somnolence	7/117 (6%)	7	6/117 (5.1%)	6	6/103 (5.8%)	6	2/83 (2.4%)	2	4/92 (4.3%)	5	3/86 (3.5%)	4
Psychiatric disorders
Insomnia	6/117 (5.1%)	8	6/117 (5.1%)	6	2/103 (1.9%)	2	0/83 (0%)	0	0/92 (0%)	0	1/86 (1.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.