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

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

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.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder
• Intervention / Treatment: Drug: Desvenlafaxine Succinate Sustained-Release Tablets (DVS SR)

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Pfizer Investigational Site
  • Florida
    • North Miami, Florida, United States, 33161
      • Pfizer Investigational Site
  • Indiana
    • Terre Haute, Indiana, United States, 47802
      • Pfizer Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67211
      • Pfizer Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10032
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44106-5080
      • Pfizer Investigational Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pfizer Investigational Site
  • Texas
    • Houston, Texas, United States, 77008
      • Pfizer Investigational Site

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 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.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A	Drug: Desvenlafaxine Succinate Sustained-Release Tablets (DVS SR); 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Children's Depression Ratings Scale-Revised (CDRS-R) Total Score	CDRS-R total score: scale measures 17 depressive symptoms, of which 3 are rated 1 to 5 and 14 are rated 1 to 7 (1 = no symptom difficulties; 5 or 7 = severe clinically significant difficulties) for a total score range of 17 to 113. Lower total scores indicate lower intensity of symptoms.	Baseline, Inpatient Days 1 to 4, Outpatient Days 5 to 7, Outpatient Weeks 2 through 8 and Outpatient Week >8 (or early termination)
Change From Baseline in Hamilton Rating Scale for Depression 17-item (HAMD-D17) Total Score	HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, & weight loss). Total score ranges from 0 to 52; higher scores reflect higher severity of current illness states.	Baseline, Inpatient Days 1 to 4, Outpatient Days 5 to 7, Outpatient Weeks 2 through 8 and Outpatient Week >8 (or early termination)
Percentage of Participants With a Categorical Clinical Global Impressions Scale-Severity (CGI-S) Score at Every Visit	CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1=normal, not ill at all, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill patients. Higher scores reflect higher severity of current illness states.	Baseline, Inpatient Days 1 to 4, Outpatient Days 5 to 7, Outpatient Weeks 2 through 8 and Outpatient Week >8 (or early termination)
Percentage of Participants With a Categorical Clinical Global Impressions Scale-Improvement(CGI-I) Score at Every Visit	CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, to 7=very much worse. Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Scores above 4 reflect worsening of illness state as compared to baseline.	Baseline, Inpatient Days 1 to 4, Outpatient Days 5 to 7, Outpatient Weeks 2 through 8 and Outpatient Week >8 (or early termination)

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (ACTUAL): November 1, 2009
• Study Completion (ACTUAL): November 1, 2009

Study Registration Dates

• First Submitted: January 28, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (ESTIMATE): February 21, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): February 23, 2011
• Last Update Submitted That Met QC Criteria: February 18, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Adolescent; Child; Outpatient; Depressive Disorder; MDD; Pediatrics; Pharmacokinetic; Major
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Desvenlafaxine Succinate
• Other Study ID Numbers: 3151A6-2000; B2061012; 3151A6-2000-US