Open-Label Study of Duloxetine in the Treatment of Children and Adolescents With Major Depressive Disorder

F1J-MC-HMFN (a) An Open-Label Study of Tolerability, Safety, and Pharmacokinetics of Duloxetine in the Treatment of Children and Adolescents With Major Depressive Disorder

The primary purpose of your participation in this study is to help answer the following research question, and not to provide you treatment for your condition. Whether duloxetine once daily orally is tolerated and safe, in children (aged 7 through 11 years) and adolescents (aged 12 through 17 years) with Major Depressive Disorder.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: duloxetine

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • 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.
  • Arizona
    • Chandler, Arizona, United States, 85226
      • 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.
  • California
    • El Centro, California, United States, 92243
      • 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.
  • Florida
    • Gainesville, Florida, United States, 32607
      • 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.
    • Miami, Florida, United States, 33180
      • 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.
    • South Miami, Florida, United States, 33143
      • 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.
  • Idaho
    • Eagle, Idaho, United States, 83616
      • 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.
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • 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.
  • Indiana
    • Terre Haute, Indiana, United States, 47802
      • 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.
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • 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.
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70816
      • 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.
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • 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.
  • New York
    • Mount Kisco, New York, United States, 10549
      • 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.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • 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.
  • Tennessee
    • Memphis, Tennessee, United States, 38117
      • 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.
  • Texas
    • Houston, Texas, United States, 77057
      • 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.
    • Lake Jackson, Texas, United States, 77566
      • 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, 78247
      • 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.
  • Virginia
    • Herndon, Virginia, United States, 20170
      • 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.
    • Midlothian, Virginia, United States, 23112
      • 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.
    • Norfolk, Virginia, United States, 23505
      • 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.
  • Washington
    • Bellevue, Washington, United States, 98004
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male / Female outpatients 7 to 17 years of age diagnosed with Major Depressive Disorder (MDD). (Must have a Children's Depression Rating Scale-Revised [CDRS-R] with a total score greater than or equal to 40 at Visit 1, Visit 2, and Visit 3 and a Clinical Global Impressions of Severity [CGI-Severity] rating of greater than or equal to 4 at Visit 1, Visit 2, and Visit 3.)
• Female patients must test negative on a pregnancy at visit 1.

Exclusion Criteria:

• Have a serious or unstable medical illness, psychological condition, clinically significant laboratory or electrocardiogram (ECG) result, hypersensitivity to duloxetine, or to its inactive ingredients, frequent or severe allergic reactions to multiple medications, uncontrolled narrow-angle glaucoma, acute liver injury (for example, hepatitis) or severe cirrhosis (Child-Pugh Class C) that in the opinion of the investigator would compromise participation in the study or be likely to lead to hospitalization during the course of the study.
• Have a current or previous diagnosis of bipolar disorder, psychotic depression, schizophrenia or other psychotic disorder, anorexia, bulimia, obsessive compulsive disorder, pervasive development disorder or borderline personality disorder, as determined by the investigator.
• Have a significant suicide attempt within 1 year of Visit 1 or have a score of 5 or greater on Item 13 (Suicidal Ideation) on the CDRS-R at Visit 1, Visit 2, or Visit 3, or are currently at risk of suicide in the opinion of the investigator.
• Have a weight less than 20 kg at any Screening Phase visit.
• Have previous exposure to duloxetine
• Female patients who are either pregnant, nursing or have recently given birth.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Duloxetine	Drug: duloxetine; 20 - 120 milligrams (mg) every day, once-daily (QD), by mouth (PO) for 30 weeks; If patient is ≤40 kilograms (kg), initial dose is 20 mg, then titrated up. If patient is >40 kg, initial dose is 30 mg, then titrated up.; Other Names: Cymbalta; LY248686

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Emergence of Suicidal Ideation During Period II/III	Emergence of Any Suicidal Ideation: Item 13 of Children's Depression Rating Scale-Revised (CDRS-R) has possible scores of 1 (no thoughts of suicide) to 7 (contemplation of suicide). Emergence of suicidal ideation was defined as an increase in severity of suicidal ideation for those patients who did not have suicidal ideation at baseline (Week 0).	Baseline to 18 weeks
Number of Participants With Emergence of Suicidal Ideation During Period IV	Emergence of Any Suicidal Ideation: Item 13 of Children's Depression Rating Scale-Revised (CDRS-R) has possible scores of 1 (no thoughts of suicide) to 7 (contemplation of suicide). Emergence of suicidal ideation was defined as an increase in severity of suicidal ideation for those patients who did not have suicidal ideation at baseline (Week 0).	Week 0 and Between 18 and 30 Weeks
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period II/III	The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.	Baseline to 18 Weeks
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) During Period IV	The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.	Between 18 and 30 Weeks
Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period II/III	Total number of patients with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Criteria: High Diastolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Systolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Pulse = increase of at least 25 to a value of at least 110.	Baseline to 18 Weeks
Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period IV	Total number of patients with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Criteria: High Diastolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Systolic Blood Pressure = increase of at least 5 mmHg to a value above the 95th percentile; High Pulse = increase of at least 25 to a value of at least 110.	Between 18 and 30 Weeks
Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period II/III	The results shown are for all laboratory analytes where PCS criteria were met, based on criteria used for adult studies. Criteria: High Alanine transaminase (>165 Units/Liter [U/L]); High Creatine Phosphokinase (females: >507 U/L; males:>594 U/L); Low Glucose (<2.498 millimoles/L); Low Hematocrit (females: <0.32; males <0.37); Low Hemoglobin (females <5.896 millimoles/L [mmol/L] iron; males <7.137 mmol/L iron); High Inorganic Phosphorus (>1.776 millimoles/L); Low Leukocyte Count (<2.8 X10^9/L).	Baseline to 18 Weeks
Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period IV	The results shown are for all laboratory analytes where PCS criteria were met, based on criteria used for adult studies. Criteria: High Alkaline Phosphatase (>420 Units/Liter [U/L]); Low Hematocrit (females <0.32; males <0.37); High Inorganic Phosphorus (>1.776 millimoles/L).	Between 18 and 30 Weeks
Number of Participants Meeting Criteria for Potentially Clinically Significant Electrocardiograms at Any Time in Period II/III	Total number of patients with any abnormal post-baseline values, based on all values at scheduled and unscheduled visits. Criteria: High QRS Interval = ≥100 milliseconds (msec); High QTc Bazette's or Fredericia's correction - Female = ≥470 msec; High QTc Bazette's or Fredericia's correction - Male = ≥450 msec.	Baseline to 18 Weeks
Number of Participants With Potentially Clinically Significant Electrocardiograms at Any Time in Period IV	Total number of patients with any abnormal post-baseline values, based on all values at scheduled and unscheduled visits. Criteria: High QRS Interval = ≥100 milliseconds (msec); High QTc Bazette's or Fredericia's correction - Female = ≥470 msec; High QTc Bazette's or Fredericia's correction - Male = ≥450 msec.	Between 18 and 30 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose	Plasma samples were obtained at steady state, and approximately 95% of duloxetine concentrations were within the 24 hour dosing interval.	Weeks 2, 4, 6, 8, 10, 14, 18
Change From Baseline to 18 Weeks and 30 Weeks in Clinical Global Impressions of Severity Scale (CGI-S)	Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Baseline is the same timepoint (Week 0) for both comparisons, but due to differences in number of patients in both periods (II/III vs IV), the baseline values may be slightly different.	Week 0 (Baseline), 18 Weeks, 30 Weeks
Change From Baseline to 18 Weeks and 30 Weeks in Children's Depression Rating Scale-Revised (CDRS-R) Total Score	Measures presence and severity of depression. Consists of 17 items scored on a 1-5 or 1-7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. In general, scores below 20 indicate an absence of depression; scores of 20 or 30 indicate borderline depression; scores of 40 to 60 indicate moderate depression. Baseline is the same timepoint (Week 0) for both comparisons, but due to differences in number of patients in both periods (II/III vs IV), the baseline values may be slightly different.	Week 0 (Baseline), 18 Weeks, 30 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events Leading to Discontinuation	A listing of adverse events leading to discontinuation from the study. Abbreviation in data table: ADHD = Attention-Deficit/Hyperactivity Disorder.	Week 0 (Baseline) to 30 Weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: September 12, 2007
• First Submitted That Met QC Criteria: September 12, 2007
• First Posted (Estimate): September 14, 2007

Study Record Updates

• Last Update Posted (Estimate): October 24, 2011
• Last Update Submitted That Met QC Criteria: October 18, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 11664; F1J-MC-HMFN (Other Identifier: Eli Lilly and Company)