Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) in the Treatment of Major Depressive Disorder

• ClinicalTrials.gov Identifier: NCT00798707
• Recruitment Status: Completed
• First Posted: November 26, 2008
• Results First Posted: June 6, 2011
• Last Update Posted: June 10, 2011
• Sponsor: Pfizer
• Information provided by: Pfizer

Tracking Information

• First Submitted Date: November 25, 2008
• First Posted Date: November 26, 2008
• Results First Submitted Date: March 7, 2011
• Results First Posted Date: June 6, 2011
• Last Update Posted Date: June 10, 2011
• Study Start Date: December 2008
• Actual Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 12, 2011)

Change From Baseline in HAM-D17 Total Score at the 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.

• Original Primary Outcome Measures (submitted: November 25, 2008): Hamilton Psychiatric Rating Scale for Depression (HAM-D 17) [ Time Frame: Approximately 10 weeks ]

Current Secondary Outcome Measures (submitted: May 12, 2011)

• 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.
• 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.
• 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).
• 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. 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.
• 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.
• 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.
• 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).
• 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.

• Original Secondary Outcome Measures (submitted: November 25, 2008): Secondary efficacy outcome measures include the CGI-I and S, MADRS and HAM-D 6. Secondary safety outcome measures include AE, suicidality and discontinuation symptom monitoring, physical and vital signs, ECGs, and changes in sexual functioning. [ Time Frame: Approximately 10 weeks ]

Current Other Pre-specified Outcome Measures (submitted: May 12, 2011)

• 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.
• Change From Baseline in SDS at FOT Evaluation (Week 8 or ET) [ Time Frame: Baseline and Week 8 (or ET) ]
  SDS: a self-administered tool 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.
• 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).
• 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 should be instructed to not complete questions 3 through 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").
• Discontinuation-Emergent Signs and Symptoms (DESS) Total Score [ 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" (1) and 0 for "old and unchanged symptom," "absent," or "old symptom but improved" for a total possible range of 0 to 43. A higher score indicates more symptoms.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) in the Treatment of Major Depressive Disorder
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of 2 Fixed Doses (25 and 50 mg/Day) of DVS SR Tablets in Adult Outpatients With Major Depressive Disorder
• Brief Summary: The primary purpose of this study is to compare the antidepressant efficacy and safety of two doses of DVS SR (25 and 50 mg/day) in the treatment of adults with Major Depressive Disorder. The study will also assess changes in sexual function and general and functional quality of life outcomes.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Major Depressive Disorder

Intervention

• Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
  25 mg tablet, once daily dosing for 8 weeks
• Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
  50 mg tablet, once daily dosing for 8 weeks
• Drug: placebo
  Matching placebo tablets (25 or 50 mg). Daily dosing for 10 +/- 4 days during a placebo lead-in period, and then 8 weeks during the double-blind period.

Study Arms

• Experimental: Desvenlafaxine succinate sustained-release 25 mg
  Intervention: Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
• Experimental: Desvenlafaxine succinate sustained-release 50 mg
  Intervention: Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
• Placebo Comparator: Placebo
  Intervention: Drug: placebo

Publications *

• 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.
• Iwata N, Tourian KA, Hwang E, Mele L, Vialet C. Efficacy and safety of desvenlafaxine 25 and 50▒mg/day in a randomized, placebo-controlled study of depressed outpatients. J Psychiatr Pract. 2013 Jan;19(1):5-14. doi: 10.1097/01.pra.0000426323.59698.64.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 27, 2010): 709
• Original Estimated Enrollment (submitted: November 25, 2008): 678
• Actual Study Completion Date: April 2010
• Actual Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)

Eligibility 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 judgement, HAM-D 17 and Columbia Suicide-Severity Rating Scale scores Other eligibility criteria also apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan, United States

Administrative Information

• NCT Number: NCT00798707
• Other Study ID Numbers: 3151A1-3359; B2061003; 3151A1-3359-WW
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

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

• PRS Account: Pfizer
• Verification Date: June 2011