Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) vs. Escitalopram in 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). This study will investigate the safety, efficacy, and tolerability of DVS SR versus escitalopram in women with major depressive disorder (MDD) who are postmenopausal.

Official Title
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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

Conditions
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Depression, Depressive Disorder, Depressive Disorder, Major

Intervention / Treatment
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* Drug: Desvenlafaxine succinate sustained-release (DVS SR)
* Drug: Escitalopram


Participation Criteria
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Eligibility Criteria
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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.

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: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br> | Drug: Desvenlafaxine succinate sustained-release (DVS SR)<br>* flexible dose of DVS 50-100 or 200 mg every day during 56 days. Extension until 6 months.<br>|
| Active Comparator: B<br> | Drug: Escitalopram<br>* Flexible dose of Escitalopram 10 or 20 mg every day during 56 days. Extension until 6 months.<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 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. | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving Response to Treatment at Final On-therapy Evaluation (Acute Phase) | 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. | 8 weeks | 
| Percentage of Patients Achieving Remission at Final On-therapy Evaluation (Acute Phase) | 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. | 8 weeks | 
| Clinical Global Impression Improvement (CGI-I) Score at 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). | 8 weeks | 
| Change in Clinical Global Impression Severity (CGI-S) Score From Baseline to Week | 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). | Baseline and 8 weeks | 
| Change in Hamilton Psychiatric Rating Scale for Anxiety From Baseline to Week 8 (HAM-A) Score | 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. | Baseline and Week 8 | 
| 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 and week 8 | 
| Percentage of Responders Maintaining Response to Treatment at Final On-therapy Evaluation (Double Blind Continuation Phase) | 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. | 6 months | 
| Percentage of Responders Achieving Remission at Final On-therapy Evaluation (Double Blind Continuation Phase) | 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. | 6 months | 
| Percentage of Responders Improving Response to Remission During 6-month Double Blind Continuation Phase | 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. | 6 months | 
| Percentage of Non-Responders Achieving Response at Final Evaluation of 6-month Open-Label (OL)Extension Phase | 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. | 6 months | 
| Percentage of Non-Responders Achieving Remission at Final Evaluation of 6-month Open-Label Extension Phase | 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. | 6 months | 
| Discontinuation-Emergent Signs and Symptoms (DESS) Total Score | 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. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDD, Major Depressive Disorder, Depression