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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Depression, Depressive Disorder, Depressive Disorder, Major

Intervention / Treatment
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* Drug: Desvenlafaxine administered as a succinate salt in a sustained-release form (DVS SR)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, vasomotor symptoms, menopause, diabetic neuropathy, fibromyalgia