Study Evaluating Desvenlafaxine Succinate Sustained-Release (DVS SR) In The Treatment Of Child And Adolescent Outpatients With Major Depressive Disorder

Study Overview
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Brief Summary
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The primary purpose of this study is to test the safety and tolerability of single ascending doses of Desvenlafaxine Succinate Sustained-Release (DVS SR) in both child and adolescent outpatients with major depressive disorder. This study will also characterize the pharmacokinetic profile of DVS SR in children and adolescents with major depressive disorder.

Official Title
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Final Report: Multicenter, Open-Label, Safety, Tolerability, And Pharmacokinetic Study To Evaluate Single Ascending Doses And Subsequent Short-Term Administration Of Fixed Doses Of DVS SR Tablets In The Treatment Of Child And Adolescent Outpatients With Major Depressive Disorder

Conditions
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Depression, Major Depressive Disorder

Intervention / Treatment
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* Drug: Desvenlafaxine Succinate Sustained-Release Tablets (DVS SR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatient between 7 and 17 years of age at baseline who meet Diagnostic and Statistic Manual of Mental Disorders, Fourth Edition, Text Revision criteria for major depressive disorder. Children's Depression Rating Scale --Revised (CDRS-R) score greater than 40 at the screening and study day -1 (baseline) visits and Clinical Global Impressions Scale--Severity (CGI-S) score of greater than or equal to 4 at the screening and study day -1 (baseline) visits. Depression of at least moderate severity with symptoms for at least 1 month before screening and that could, in the investigator's opinion, respond to therapy with antidepressant(s) alone (without concomitant psychotherapy). Other inclusion criteria apply. Exclusion Criteria: History or current evidence of a medical condition known to interfere with the absorption or excretion of drugs or a history of surgery known to interfere with the absorption or excretion of drugs; history or presence of any other medical condition that might confound the study or put the study participant at greater risk during participation; known hypersensitivity to venlafaxine. History of suicide attempt or gesture in which the intent was suicide or serious self-harm or acute suicidality to such a degree that precaution against suicide must be exercised. Current (within 12 months before baseline) psychoactive substance abuse or dependence (including alcohol), manic episode, posttraumatic stress disorder, obsessive-compulsive disorder, or a diagnosis of bipolar disorder or psychotic disorder or current (within 12 months before baseline) generalized anxiety disorder, panic disorder, social anxiety disorder, or attention deficit hyperactivity disorder (ADHD) if considered by the investigator to be primary (causing a higher degree of distress or impairment than MDD) or presence (within 12 months before baseline) of a clinically important personality disorder (such as antisocial, schizotypal, histrionic, borderline, or narcissistic) as assessed during the psychiatric evaluations or history or presence of MDD with psychotic features. Other exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Desvenlafaxine Succinate Sustained-Release Tablets (DVS SR)<br>* DVS SR Tablets of 10mg, 25mg, 50mg, and 100mg. Assigned DVS SR daily doses of 10mg, 25mg, 50mg, 100mg, or 200mg for up to 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events AEs) and Serious Adverse Events (SAEs) | AEs are any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study treatment. The event does not need to be causally related to the study treatment. SAEs are adverse events that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in persistent or significant disability or incapacity, result in cancer, or result in a congenital anomaly or birth defect. | Baseline to Follow-up (up to Day 77) | 
| Maximum Observed Plasma Concentration (Cmax) | Noncompartmental pharmacokinetic (PK) parameter obtained using 0 to 72 hour concentration data from venous blood samples measured as nanograms per milliliter (ng/mL). | Pre-dose (0 hour) and Post-dose (0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours) on Days 28 and 56 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Noncompartmental PK parameter obtained using 0 to 72 hour concentration data from venous blood samples measured as hours (hr). | Pre-dose (0 hour) and Post-dose (0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours) on Days 28 and 56 | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Noncompartmental PK parameter obtained using 0 to 72 hour concentration data from venous blood samples measured as hours (hr). | Pre-dose (0 hour) and Post-dose (0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours) on Days 28 and 56 | 
| Area Under the Curve From Time Zero to Infinity (AUC0-∞) | AUC (0-∞) = Area under the plasma concentration versus time curve from time zero (pre-dose) to infinity. Noncompartmental PK parameter obtained using 0 to 72 hour concentration data from venous blood samples measured as nanograms multiplied by hours divided by milliliters (ng*hr/mL). | Pre-dose (0 hour) and Post-dose (0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours) on Days 28 and 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population Pharmacokinetics Dose Normalized AUC (AUC/D): First Method, Second Method | Relationship of variables (i.e., age, sex, ethnicity, and food) examined by fitting dose normalized AUC (AUC/D) values to a power model. AUC/D regressed against variables using power equation Y=A*W^b (Y=AUC/D; A=coefficient; W=variable; b=exponent). AUC values from children cohort (ages 7 to 11) combined doses=first method of analysis. AUC from adolescent cohort (ages 12 to 17) combined doses=second method of analysis. AUC values combined from both cohorts=third method of analysis. Measured as nanograms multiplied by hours divided by milliliters per milligram of dose [(ng*hr/mL)/mg of dose]. | Day 1, Day 28, and Day 56 | 
| Population Pharmacokinetics Dose Normalized AUC (AUC/D): Third Method | Relationship of variables (i.e., age, sex, ethnicity, and food) examined by fitting dose normalized AUC (AUC/D) values to a power model. AUC/D regressed against variables using power equation Y=A*W^b (Y=AUC/D; A=coefficient; W=variable; b=exponent). AUC values from children cohort (ages 7 to 11) combined doses=first method of analysis. AUC from adolescent cohort (ages 12 to 17) combined doses=second method of analysis. AUC values combined from both cohorts=third method of analysis. Measured as nanograms multiplied by hours divided by milliliters per milligram of dose [(ng*hr/mL)/mg of dose]. | Day 1, Day 28, and Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDD, Child, Adolescent, Pharmacokinetic, Outpatient, Pediatrics, Depressive Disorder, Major