Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) vs. Escitalopram in Postmenopausal Women

• ClinicalTrials.gov Identifier: NCT00406640
• Recruitment Status: Completed
• First Posted: December 4, 2006
• Results First Posted: June 29, 2010
• Last Update Posted: June 29, 2010
• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Information provided by: Wyeth is now a wholly owned subsidiary of Pfizer

Tracking Information

• First Submitted Date: November 29, 2006
• First Posted Date: December 4, 2006
• Results First Submitted Date: February 27, 2009
• Results First Posted Date: June 29, 2010
• Last Update Posted Date: June 29, 2010
• Study Start Date: December 2006
• Actual Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 26, 2010)

Change in Hamilton Psychiatric Rating Scale for Depression (HAM-D17) Score From Baseline to Week 8 [ Time Frame: Baseline and 8 weeks ]

HAM-D17 is 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. Change= 8 week adjusted mean HAM-D17 minus baseline adjusted mean HAM-D17.

• Original Primary Outcome Measures (submitted: November 29, 2006): To assess efficacy measured by the change from baseline on the Hamilton Rating Scale for Depression total score over 8 weeks of treatment with DVS SR compared to treatment with escitalopram in postmenopausal women with MDD.

Current Secondary Outcome Measures (submitted: May 26, 2010)

• Percentage of Patients Achieving Response to Treatment at Final On-therapy Evaluation (Acute Phase) [ Time Frame: 8 weeks ]
  A response is defined as ≥ 50% decrease from baseline on Hamilton Psychiatric Rating Scale for Depression (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 a 0 to 2 or 4 scale (0=none/absent and 4=most severe) for a maximum total score of 50.
• Percentage of Patients Achieving Remission at Final On-therapy Evaluation (Acute Phase) [ Time Frame: 8 weeks ]
  Remission is defined as a Hamilton Psychiatric Rating Scale for Depression (HAM-D17) score of ≤ 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on a 0 to 2 or 4 scale (0=none/absent and 4=most severe) for a maximum total score of 50.
• Clinical Global Impression Improvement (CGI-I) Score at 8 Weeks [ Time Frame: 8 weeks ]
  CGI-I is a global rating scale that measures disease improvement. Using a 7-point scale, the clinician rates how much the patient's illness has improved or worsened relative to the baseline status (1= very much improved; 7= very much worse).
• Change in Clinical Global Impression Severity (CGI-S) Score From Baseline to Week [ Time Frame: Baseline and 8 weeks ]
  CGI-S is a global rating scale that measures the severity of a patient's disease. Using a 7-point scale, the clinician rates the severity of the patient's mental illness at the time of the assessment, relative to the clinician's experience with patients who have the same diagnosis (1= normal; 7= extremely ill).
• Change in Hamilton Psychiatric Rating Scale for Anxiety From Baseline to Week 8 (HAM-A) Score [ Time Frame: Baseline and Week 8 ]
  The HAM-A is a standardized, clinician-administered rating scale that assesses 14 items characteristically associated with major anxiety disorders. Items are scaled 0 - 4 (0=none and 4=very severe), with a maximum total score of 56. Change= 8 week adjusted mean HAM-A total score minus baseline adjusted mean total score.
• Change in Dimension Health State EuroQol (EQ-5D) Score From Baseline to Week 8 [ Time Frame: Baseline and week 8 ]
  EQ-5D is a standardized, subject-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health). Change=8 week score minus baseline score.
• Percentage of Responders Maintaining Response to Treatment at Final On-therapy Evaluation (Double Blind Continuation Phase) [ Time Frame: 6 months ]
  Patients achieving a response to treatment at the end of the 8-week acute double blind (DB) phase continued the same treatment in a 6-month DB continuation phase and were evaluated to see if the response was maintained. A response is defined as ≥ 50% decrease from baseline on Hamilton Psychiatric Rating Scale for Depression (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 a 0 to 2 or 4 scale (0=none/absent and 4=most severe) for a maximum total score of 50.
• Percentage of Responders Achieving Remission at Final On-therapy Evaluation (Double Blind Continuation Phase) [ Time Frame: 6 months ]
  Patients achieving a response to treatment at the end of the 8-week acute double blind (DB) phase continued the same treatment in a 6-month DB continuation phase and were evaluated to see if remission was achieved. Remission is defined as a Hamilton Psychiatric Rating Scale for Depression (HAM-D17) score of ≤ 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on a 0 to 2 or 4 scale (0=none/absent and 4=most severe) for a maximum total score of 50.
• Percentage of Responders Improving Response to Remission During 6-month Double Blind Continuation Phase [ Time Frame: 6 months ]
  Patients achieving a response to treatment (Responders) at the end of the 8-week acute double blind (DB) phase continued into a 6-month DB phase. Responders without remission at 8 weeks were assessed for remission status during the 6-month continuation. Remission defined as a Hamilton Psychiatric Rating Scale for Depression (HAM-D17) score ≤ 7. HAM-D17 is a standardized, clinician-administered rating scale assessing 17 items characteristically associated with major depression. Individual items scored on a 0 to 2 or 4 scale (0=none/absent and 4=most severe) for a maximum total score of 50.
• Percentage of Non-Responders Achieving Response at Final Evaluation of 6-month Open-Label (OL)Extension Phase [ Time Frame: 6 months ]
  Patients who didn't achieve a response to treatment at the end of the 8-week acute double blind phase entered into an OL treatment phase with DVS SR for 6 months and were evaluated to see if a response was achieved. A response is defined as ≥ 50% decrease from baseline on Hamilton Psychiatric Rating Scale for Depression (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 a 0 to 2 or 4 scale (0=none/absent and 4=most severe) for a maximum total score of 50.
• Percentage of Non-Responders Achieving Remission at Final Evaluation of 6-month Open-Label Extension Phase [ Time Frame: 6 months ]
  Patients who did not achieve a response to treatment at the end of the 8-week acute double blind phase entered into an open label (OL) treatment phase with DVS SR for 6 months and were evaluated to see if remission was achieved. Remission is defined as a Hamilton Psychiatric Rating Scale for Depression (HAM-D17) score of ≤ 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on a 0 to 2 or 4 scale (0=none/absent and 4=most severe) for a maximum total score of 50.
• Discontinuation-Emergent Signs and Symptoms (DESS) Total Score [ Time Frame: 6 months ]
  DESS is 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. The DESS score was assessed by status of taper.

• Original Secondary Outcome Measures (submitted: November 29, 2006): To compare DVS SR to escitalopram with respect to remission and response rates, anxiety scores, quality of life, safety, and tolerability.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) vs. Escitalopram in Postmenopausal Women
• Official Title: A Multicenter, Randomized, 8-Week Double-Blind Acute Phase Followed By a 6-Month Continuation Phase (Open-Label Or Double-Blind) Study to Evaluate the Efficacy, Safety, and Tolerability of DVS SR Versus Escitalopram in Postmenopausal Women With Major Depressive Disorder
• Brief Summary: Desvenlafaxine succinate (DVS) is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI). This study will investigate the safety, efficacy, and tolerability of DVS SR versus escitalopram in women with major depressive disorder (MDD) who are postmenopausal.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

• Drug: Desvenlafaxine succinate sustained-release (DVS SR)
  flexible dose of DVS 50-100 or 200 mg every day during 56 days. Extension until 6 months.
• Drug: Escitalopram
  Flexible dose of Escitalopram 10 or 20 mg every day during 56 days. Extension until 6 months.

Study Arms

• Active Comparator: A
  Intervention: Drug: Desvenlafaxine succinate sustained-release (DVS SR)
• Active Comparator: B
  Intervention: Drug: Escitalopram

• Publications *: Soares CN, Thase ME, Clayton A, Guico-Pabia CJ, Focht K, Jiang Q, Kornstein SG, Ninan PT, Kane CP. Open-label treatment with desvenlafaxine in postmenopausal women with major depressive disorder not responding to acute treatment with desvenlafaxine or escitalopram. CNS Drugs. 2011 Mar;25(3):227-38. doi: 10.2165/11586460-000000000-00000.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 26, 2010): 595
• Original Enrollment (submitted: November 29, 2006): 500
• Actual Study Completion Date: October 2008
• Actual Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Postmenopausal women between the ages of 40 and 70 years, inclusive.
• A primary diagnosis of MDD, single or recurrent episode, without psychotic features using the modified MINI International Neuropsychiatric Interview (MINI).
• Montgomery-Asberg Depression Rating Scale (MADRS) total score > or = 22 at the screening and baseline visit.

Exclusion Criteria:

• Use of oral estrogen-, progestin-, androgen-, or Selective Estrogen Receptor Modulator (SERM)-containing drug products 8 weeks before baseline.
• Current (within 12 months) psychoactive substance abuse or dependence (including alcohol), manic episode, post-traumatic stress disorder, obsessive-compulsive disorder, or a lifetime diagnosis of bipolar or psychotic disorder.
• A history or active presence of clinically important medical disease.

Additional criteria apply.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 40 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Chile, Colombia, Mexico, Peru, United States

Administrative Information

• NCT Number: NCT00406640
• Other Study ID Numbers: 3151A1-402
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Wyeth (Registry Contact: Clinical Trial Registry Specialist), Wyeth
• Study Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor; Wyeth is now a wholly owned subsidiary of Pfizer
• Principal Investigator: Trial Manager; For Argentina: Scheima@wyeth.com
• Principal Investigator: Trial Manager; For Chile: scheima@wyeth.com
• Principal Investigator: Trial Manager; For Mexico: gomezzlj@wyeth.com

• PRS Account: Wyeth is now a wholly owned subsidiary of Pfizer
• Verification Date: May 2010