Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) Versus Placebo in Peri- and Postmenopausal Women

A Multicenter, Randomized, 8-week, Double-blind, Placebo-controlled Study Followed by a 6-month Open-label Extension to Evaluate the Efficacy and Safety of DVS SR in Peri- and Postmenopausal Women With Major Depressive Disorder

Desvenlafaxine succinate (DVS) is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI). The sustained-release (SR) formulation, DVS SR, is being studied in the development program for the treatment of major depressive disorder (MDD), for vasomotor symptoms (VMS) associated with menopause, and for pain associated with peripheral diabetic neuropathy, as well as for the treatment of fibromyalgia syndrome. This study will investigate the safety, efficacy, and tolerability of DVS SR in women with MDD who are peri- and postmenopausal.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder; Depression; Depressive Disorder, Major
• Intervention / Treatment: Drug: Desvenlafaxine administered as a succinate salt in a sustained-release form (DVS SR); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 381
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35226
  • Arkansas
    • Little Rock, Arkansas, United States, 72223
    • Springdale, Arkansas, United States, 72762
  • California
    • Palo Alto, California, United States, 94305
    • San Diego, California, United States, 92103
  • Connecticut
    • New London, Connecticut, United States, 06320
  • Florida
    • Bradenton, Florida, United States, 34208
    • Miami, Florida, United States, 33133
    • Tampa, Florida, United States, 33613
    • Winter Park, Florida, United States, 32789
  • Georgia
    • Atlanta, Georgia, United States, 30308
    • Sandy Springs, Georgia, United States, 30328
    • Savannah, Georgia, United States, 31406
    • Smyrna, Georgia, United States, 30080
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
  • Illinois
    • Chicago, Illinois, United States, 60634
  • Indiana
    • Indianapolis, Indiana, United States, 46202
    • Terre Haute, Indiana, United States, 47802
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
  • Maryland
    • Rockville, Maryland, United States, 20852
  • Nebraska
    • Omaha, Nebraska, United States, 68131
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
  • New York
    • Brooklyn, New York, United States, 11235
  • North Dakota
    • Minot, North Dakota, United States, 58701
  • Ohio
    • Beachwood, Ohio, United States, 44122
    • Dayton, Ohio, United States, 45408
    • Toledo, Ohio, United States, 43623
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73118
    • Tulsa, Oklahoma, United States, 74135
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19131
  • South Carolina
    • Hilton Head Island, South Carolina, United States, 29926
  • Texas
    • Austin, Texas, United States, 78756
    • Houston, Texas, United States, 77007
  • Virginia
    • Richmond, Virginia, United States, 23230
    • Richmond, Virginia, United States, 23229
  • Washington
    • Seattle, Washington, United States, 98105
  • Wisconsin
    • Brown Deer, Wisconsin, United States, 53223

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Peri- and 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: Desvenlafaxine administered as a succinate salt in a sustained-release form (DVS SR); DVS-SR 50-200mg, daily (QD), tablet form, treatment period up to 34 weeks
Placebo Comparator: B	Drug: Placebo; Placebo, daily (QD), tablet form, treatment period up to 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton Psychiatric Rating Scale for Depression (HAM-D17) Score From Baseline to Week 8.	HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50. Change= 8 week adjusted mean HAM-D17 minus baseline adjusted mean HAM-D17	Baseline to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Each Clinical Global Impression Improvement (CGI-I) Score	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).	8 weeks
Percentage of Patients Achieving Remission	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. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50.	8 weeks
Percentage of Patients Achieving Response to Treatment	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. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50.	8 weeks
Change in Hamilton Psychiatric Rating Scale for Anxiety (HAM-A) Score From Baseline to 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 score minus baseline adjusted mean score.	Baseline to 8 weeks
Change in Dimension Health State EuroQol (EQ-5D) Score From Baseline to 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.	Baseline to 8 weeks
Change in Hamilton Psychiatric Rating Scale for Depression (HAM-D17) Score From Open Label Baseline to 6 Months	HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total s core of 50. Change= Final Evaluation mean HAM-D17 minus baseline mean HAM-D17.	open label baseline and 6 months
Clinical Global Impression Improvement (CGI-I) Score	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)	6 months
Percentage of Patients Achieving Remission	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. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total s core of 50.	6 months
Percentage of Patients Achieving a Response to Treatment	A responder is defined as a patient with ≥ 50% decrease from baseline on Hamilton Psychiatric Rating Scale for Depression - 17-item (HAM-D17) score. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50.	6 months
Change in Hamilton Psychiatric Rating Scale for Anxiety (HAM-A) Score From Open Label Baseline to 6 Months	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= Final Evaluation mean HAM-A score minus baseline mean score.	open label baseline to 6 months
Change in Dimension Health State EuroQol (EQ-5D) Score From Open Label Baseline to 6 Months	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.	open label baseline to 6 months
Discontinuation-Emergent Signs and Symptoms (DESS) Total Score	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.	6 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Kornstein SG, Clayton AH, Bao W, Guico-Pabia CJ. A pooled analysis of the efficacy of desvenlafaxine for the treatment of major depressive disorder in perimenopausal and postmenopausal women. J Womens Health (Larchmt). 2015 Apr;24(4):281-90. doi: 10.1089/jwh.2014.4900.
• Kornstein SG, Jiang Q, Reddy S, Musgnung JJ, Guico-Pabia CJ. Short-term efficacy and safety of desvenlafaxine in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder. J Clin Psychiatry. 2010 Aug;71(8):1088-96. doi: 10.4088/JCP.10m06018blu.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: August 25, 2006
• First Submitted That Met QC Criteria: August 25, 2006
• First Posted (Estimate): August 29, 2006

Study Record Updates

• Last Update Posted (Estimate): May 7, 2012
• Last Update Submitted That Met QC Criteria: April 9, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: vasomotor symptoms; menopause; fibromyalgia; Major Depressive Disorder; diabetic neuropathy
• 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: 3151A1-403