E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
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E.1.1.1 | Medical condition in easily understood language |
Major Depressive Disorder |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025454 |
E.1.2 | Term | Major depressive disorder, recurrent episode |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of duloxetine delivered orally, in children (aged 7 through 11 years) and adolescents (aged 12 through 17 years) who met criteria for MDD without psychotic features, single or recurrent, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV [APA 1994]) and confirmed by the Kiddie-SADS - Lifetime Version (K‑SADS-PL). |
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E.2.2 | Secondary objectives of the trial |
• To characterize the pharmacokinetics of duloxetine at steady-state in children and adolescents. The characterization included an estimation of duloxetine pharmacokinetic parameters, determination of inter-patient and intra-patient variability, and identification of potential patient factors (age, body weight, maturation, gender, nicotine exposure, and CYP2D6 genotype status) that may have influenced duloxetine pharmacokinetics as measured by steady-state duloxetine plasma concentrations.
• To compare the steady-state duloxetine pharmacokinetics in children and adolescents with historical adult duloxetine pharmacokinetics using duloxetine steady-state concentration data and pharmacokinetic parameters.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome Measures:
•Number of Participants With Emergence of Suicidal Ideation During Period II/III [ Time Frame: Baseline to 18 weeks ]
•Number of Participants With Emergence of Suicidal Ideation During Period IV [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Between 18 and 30 Weeks ]
•Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period II/III [ Time Frame: Baseline to 18 Weeks ]
•Number of Participants Meeting Criteria for Potentially Clinically Significant Vital Sign Values at Any Time During Period IV [ Time Frame: 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 [ Time Frame: Baseline to 18 Weeks ]
•Number of Participants Meeting Criteria for Potentially Clinically Significant (PCS) Laboratory Analyte Values at Any Time During Period IV [ Time Frame: Between 18 and 30 Weeks ]
•Number of Participants Meeting Criteria for Potentially Clinically Significant Electrocardiograms at Any Time in Period II/III [ Time Frame: Baseline to 18 Weeks ]
•Number of Participants With Potentially Clinically Significant Electrocardiograms at Any Time in Period IV [ Time Frame: Between 18 and 30 Weeks ] |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
18-30 weeks from baseline |
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E.5.2 | Secondary end point(s) |
•Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose
•Change From Baseline to 18 Weeks and 30 Weeks in Clinical Global Impressions of Severity Scale (CGI-S)
•Change From Baseline to 18 Weeks and 30 Weeks in Children's Depression Rating Scale-Revised (CDRS-R) Total Score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Pharmacokinetics: Summary of Observed Duloxetine Plasma Concentrations Stratified by Duloxetine Dose [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Week 0 (Baseline), 18 Weeks, 30 Weeks ]
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |