Study Evaluating Desvenlafaxine Succinate Sustained Release In Adults With Major Depressive Disorder

• ClinicalTrials.gov Identifier: NCT00863798
• Recruitment Status: Completed
• First Posted: March 18, 2009
• Results First Posted: May 6, 2011
• Last Update Posted: May 6, 2011
• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborator: Pfizer
• Information provided by: Wyeth is now a wholly owned subsidiary of Pfizer

Study Description

Brief Summary:

The primary purpose of this study is to compare the antidepressant efficacy and safety of two doses of desvenlafaxine succinate sustained release (10 and 50 mg/day) in adults with Major Depressive Disorder. The study will also assess changes in sexual function and general and functional quality of life outcomes.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Desvenlafaxine Succinate Sustained-Release 10mg; Drug: Desvenlafaxine Succinate Sustained-Release 50 mg; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 682 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study To Evaluate The Efficacy And Safety Of 2 Fixed Doses (10 And 50 mg/Day) Of DVS SR Tablets In Adult Outpatients With Major Depressive Disorder
• Study Start Date: April 2009
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Desvenlafaxine succinate sustained release 10 mg	Drug: Desvenlafaxine Succinate Sustained-Release 10mg; 10 mg tablet, once daily dosing for 8 weeks
Experimental: Desvenlafaxine succinate sustained release 50 mg	Drug: Desvenlafaxine Succinate Sustained-Release 50 mg; 50 mg tablet, once daily dosing for 8 weeks
Placebo Comparator: Placebo	Drug: placebo; Matching placebo tablets (10 or 50mg). Daily dosing for 10 +/- 4 days during a placebo lead-in period, and then 8 weeks during the double-blind period.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in HAM-D17 Total Score at Final On-therapy (FOT) Evaluation (Week 8 or ET) [ Time Frame: Baseline and Week 8 (or ET) ]
   HAM-D17: a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.

Secondary Outcome Measures :

1. Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET) [ Time Frame: Week 8 (or ET) ]
   CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) 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. Higher score = more affected.
2. Change From Baseline in Mean CGI-S Score at FOT Evaluation (Week 8 or ET) [ Time Frame: Baseline and Week 8 (or ET ) ]
   CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.
3. Change From Baseline in MADRS Total Score at FOT Evaluation (Week 8 or ET) [ Time Frame: Baseline and Week 8 (or ET) ]
   MADRS measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
4. Change From Baseline in HAM-D6 Total Score at FOT Evaluation (Week 8 or ET) [ Time Frame: Baseline and Week 8 (or ET ) ]
   HAM-D6: a standardized, clinician-administered rating scale that assesses 6 items characteristically associated with major depression and is a subset of HAM-D17. HAM-D6 score ranges from 0-22. 0=none/absent and 22=most severe.The scale uses HAM-D17 items: 1, 2, 7, 8, 10 and 13. Item 13 is scored 0-2 and all others are scored 0-4.
5. Number of Participants With a Response on the HAM-D17 at FOT Evaluation (Week 8 or ET) [ Time Frame: Week 8 (or ET) ]
   A HAM-D17 responder was defined as a participant with a 50% or greater decrease from baseline in HAM-D17 score. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.
6. Number of Participants in Remission Based on the HAM-D17 at FOT Evaluation (Week 8 or ET) [ Time Frame: Week 8 (or ET) ]
   Remission was defined as a HAM-D17 score of less than or equal to 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.
7. Number of Participants With a Response on the MADRS Score at FOT Evaluation (Week 8 or ET) [ Time Frame: Week 8 (or ET) ]
   A MADRS responder was defined as a participant with a 50% or greater decrease from baseline in MADRS score. It measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
8. Number of Participants With a Response on the CGI-I Score at FOT Evaluation (Week 8 or ET) [ Time Frame: Week 8 (or ET) ]
   CGI-I responder was defined as a participant with a score of 1 (very much improved) or 2 (much improved) on the CGI-I. CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) 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. Higher score = more affected.

Other Outcome Measures:

1. Population Pharmacokinetics for Desvenlafaxine Plasma Concentrations [ Time Frame: Week 2, 4 and 8 (or ET) ]
   Relationship of demographic variables (age, gender, food, race, creatinine, aspartate aminotransaminase, alanine transaminase, bilirubin and concomitant medications) were examined by fitting measured DVS plasma concentrations to a 1 compartment model with first order absorption. Demographic variables were examined for clearance (CL/F), volume of distribution (V/F), Steady Area under Curve (AUC) using nonlinear mixed effects modeling. Final parameter estimates for demographic factors effecting CL/F, V/F and AUC were determined.
2. Change From Baseline in SDS at FOT Evaluation (Week 8 or ET) [ Time Frame: Baseline and Week 8 (or ET) ]
   SDS: a self-administered tools that measures functional impairment in 3 domains: Work/School, Social Life, and Family Life/Home Responsibilities. The participant rates the extent to which each of these domains is impaired by his/her symptoms using a 10 point visual analog scale: (0=not at all impaired, 10=extremely impaired) for a total maximum score of 30.
3. Change From Baseline in WHO-5 Total Score at FOT Evaluation (Week 8 or ET) [ Time Frame: Baseline and Week 8 (or ET) ]
   WHO-5 evaluates positive psychological well-being. WHO-5 consists of 5 questions and each is rated on a 6-point scale. The total score ranges from 0 to 25 (0= worst possible quality of life; 25=best possible quality of life).
4. Percentage of Participants With Sexual Dysfunction at FOT Evaluation (Week 8 or ET) [ Time Frame: Week 8 (or ET) ]
   ASEX scale includes 5 questions that evaluate sexual function exclusively during the week prior to completion in the following areas: libido, excitability and ability to reach orgasm. Sexual dysfunction=an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items. Participants who have had no sexual activity during the prior week were instructed to not complete questions 3 through 5.
5. Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET) [ Time Frame: Week 8 (or ET) ]
   C-SSRS mapped into C-CASA(1-7) to assess whether participant:completed suicide(1),suicide attempt(2)(response of "Yes" on "Actual Attempt"),preparatory acts toward imminent suicidal behavior (3)("Yes" on "Preparatory Acts or Behavior"),suicidal ideation (4)("Yes" on "Wish to be dead","Non-Specific Active Suicidal Thoughts","Active Suicidal Ideation with methods without Intent to Act or Some Intent to Act,without Specific Plan or with Specific Plan and Intent),any suicidal behavior or ideation,self-injurious behaviour(7)("Yes" on "Has subject engaged in Non-suicidal Self-Injurious Behavior").
6. Discontinuation-Emergent Signs and Symptoms (DESS) [ Time Frame: Week 8 to 10 (or ET) ]
   DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of new symptoms and old (but worse) symptoms that appeared during tapering of the test article. A higher score indicates more symptoms.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adult, outpatient with primary diagnosis of Major Depressive Disorder (depressive symptoms for at least 30 days prior to screening).
• Hamilton Psychiatric Rating Scale for Depression (HAM-D 17) total score of >= 20.
• Clinical Global Impressions Scale-Severity (CGI-S) score of >= 4.

Exclusion Criteria:

• Clinical instability (25% or greater increase/decrease in HAM-D 17 total score from screening to baseline).
• Significant risk of suicide as assessed by clinician judgment, HAM-D 17 and Columbia Suicide-Severity Rating Scale scores Other eligibility criteria also apply.

Contacts and Locations

Locations

United States, Alabama

Pfizer Investigational Site

Birmingham, Alabama, United States, 35216

United States, California

Pfizer Investigational Site

Encino, California, United States, 91316

Pfizer Investigational Site

Newport Beach, California, United States, 92660

Pfizer Investigational Site

Redlands, California, United States, 92374

Pfizer Investigational Site

Upland, California, United States, 91786

United States, Colorado

Pfizer Investigational Site

Aurora, Colorado, United States, 80045

Pfizer Investigational Site

Denver, Colorado, United States, 80204

United States, Connecticut

Pfizer Investigational Site

Cromwell, Connecticut, United States, 06416

United States, Florida

Pfizer Investigational Site

Maitland, Florida, United States, 32751

Pfizer Investigational Site

North Miami, Florida, United States, 33161

Pfizer Investigational Site

South Miami, Florida, United States, 33143

United States, Indiana

Pfizer Investigational Site

Indianapolis, Indiana, United States, 46260

United States, Missouri

Pfizer Investigational Site

St. Louis, Missouri, United States, 63139

United States, New York

Pfizer Investigational Site

New York, New York, United States, 10128

Pfizer Investigational Site

Staten Island, New York, United States, 10312

United States, Ohio

Pfizer Investigational Site

Toledo, Ohio, United States, 43623

United States, Oregon

Pfizer Investigational Site

Eugene, Oregon, United States, 97401

Pfizer Investigational Site

Portland, Oregon, United States, 97210

Pfizer Investigational Site

Salem, Oregon, United States, 97301

United States, Pennsylvania

Pfizer Investigational Site

Media, Pennsylvania, United States, 19063

United States, Virginia

Pfizer Investigational Site

Herndon, Virginia, United States, 20170

Pfizer Investigational Site

Midlothian, Virginia, United States, 23112

United States, Wisconsin

Pfizer Investigational Site

Middleton, Wisconsin, United States, 53562

Pfizer Investigational Site

Waukesha, Wisconsin, United States, 53188

Sponsors and Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zilcha-Mano S, Wang X, Wajsbrot DB, Boucher M, Fine SA, Rutherford BR. Trajectories of Function and Symptom Change in Desvenlafaxine Clinical Trials: Toward Personalized Treatment for Depression. J Clin Psychopharmacol. 2021 Sep-Oct 01;41(5):579-584. doi: 10.1097/JCP.0000000000001435.

Soares CN, Zhang M, Boucher M. Categorical improvement in functional impairment in depressed patients treated with desvenlafaxine. CNS Spectr. 2019 Jun;24(3):322-332. doi: 10.1017/S1092852917000633. Epub 2017 Nov 15.

McIntyre RS, Fayyad R, Mackell JA, Boucher M. Effect of metabolic syndrome and thyroid hormone on efficacy of desvenlafaxine 50 and 100 mg/d in major depressive disorder. Curr Med Res Opin. 2016;32(3):587-99. doi: 10.1185/03007995.2015.1136603. Epub 2016 Jan 13.

McIntyre RS, Fayyad RS, Guico-Pabia CJ, Boucher M. A Post Hoc Analysis of the Effect of Weight on Efficacy in Depressed Patients Treated With Desvenlafaxine 50 mg/d and 100 mg/d. Prim Care Companion CNS Disord. 2015 Jun 4;17(3). doi: 10.4088/PCC.14m01741. eCollection 2015.

Thase ME, Fayyad R, Cheng RF, Guico-Pabia CJ, Sporn J, Boucher M, Tourian KA. Effects of desvenlafaxine on blood pressure in patients treated for major depressive disorder: a pooled analysis. Curr Med Res Opin. 2015 Apr;31(4):809-20. doi: 10.1185/03007995.2015.1020365. Epub 2015 Mar 26.

Soares CN, Endicott J, Boucher M, Fayyad RS, Guico-Pabia CJ. Predictors of functional response and remission with desvenlafaxine 50 mg/d in patients with major depressive disorder. CNS Spectr. 2014 Dec;19(6):519-27. doi: 10.1017/S1092852914000066. Epub 2014 Feb 26.

Liebowitz MR, Tourian KA, Hwang E, Mele L; Study 3362 Investigators. A double-blind, randomized, placebo-controlled study assessing the efficacy and tolerability of desvenlafaxine 10 and 50 mg/day in adult outpatients with major depressive disorder. BMC Psychiatry. 2013 Mar 22;13:94. doi: 10.1186/1471-244X-13-94.

• Responsible Party: Director, Clinical Trial Disclosure Group, Wyeth
• ClinicalTrials.gov Identifier: NCT00863798
• Other Study ID Numbers: 3151A1-3362; B2061005; 3151A1-3362-US
• First Posted: March 18, 2009
• Results First Posted: May 6, 2011
• Last Update Posted: May 6, 2011
• Last Verified: April 2011

Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer:

Major Depressive Disorder

Additional relevant MeSH terms:

Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Pathologic Processes; Mood Disorders; Mental Disorders; Behavioral Symptoms; Desvenlafaxine Succinate; Serotonin and Noradrenaline Reuptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Physiological Effects of Drugs; Antidepressive Agents; Psychotropic Drugs