Paroxetine-referenced Study Evaluating Three Doses of DVS SR in Outpatients With MDD

Study Overview
=================
Brief Summary
-----------------
This study will assess the safety, tolerability and efficacy of desvenlafaxine succinate sustained release (DVS SR) in subjects with major depressive disorder.

Detailed Description
-----------------
The primary objective of this study is to investigate the efficacy, safety and tolerability of desvenlafaxine succinate sustained release (DVS SR) in Chinese, Taiwanese, South Korean, and Indian subjects with major depressive disorder (MDD) receiving daily doses of 50 mg, 100 mg, or 200 mg. The secondary objective is to obtain additional information regarding the efficacy of DVS SR in subjects with MDD receiving daily doses of 50 mg, 100 mg, or 200 mg. Additional objectives include obtaining general and functional quality of life outcome data.

Official Title
-----------------
A Multicenter, Randomized, Double-blind, Paroxetine-referenced, Parallel-group Study to Evaluate the Safety, Efficacy, and Tolerability of 3 Fixed Doses (50mg, 100mg, AND 200mg) of Desvenlafaxine Succinate Sustained-release Tablets in Adult Outpatients With Major Depressive Disorder

Conditions
-----------------
Depressive Disorder, Major

Intervention / Treatment
-----------------
* Drug: DVS SR
* Drug: Paroxetine


Participation Criteria
=================
Eligibility Criteria
-----------------
Primary Inclusion Criteria: Outpatient men and women at least 18 years of age. Have a primary diagnosis of MDD based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV), single or recurrent episode, without psychotic features. Have a HAM D17 total score ≥20 at the screening and baseline (study day 1) visit. Primary Exclusion Criteria: Treatment with DVS SR at any time in the past. Significant risk of suicide based on clinical judgment, including common suicidal thoughts and suicide having been considered as a possible solution even without specific plans or intent. Any unstable hepatic, renal, pulmonary, cardiovascular (including uncontrolled hypertension), ophthalmologic, neurologic, or any other medical condition that might confound the study or put the subject at greater risk during study participation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>DVS SR 50mg/day | Drug: DVS SR<br>* Arm 1: 50mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper Arm 2: 100mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper Arm 3: 200mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper<br>|
| Experimental: B<br>DVS SR 100mg/day | Drug: DVS SR<br>* Arm 1: 50mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper Arm 2: 100mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper Arm 3: 200mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper<br>|
| Experimental: C<br>DVS SR 200mg/day | Drug: DVS SR<br>* Arm 1: 50mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper Arm 2: 100mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper Arm 3: 200mg DVS SR tablet, QD, 8 weeks treatment with 2 week taper<br>|
| Active Comparator: D<br>Paroxetine 20mg/day | Drug: Paroxetine<br>* 20 mg Paroxetine capsule, QD, 8 weeks treatment with 2 week taper<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders With a 50% or Greater Decrease From Baseline on the Hamilton Rating Scale for Depression, 17-item (HAM-D17) | 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. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impressions Scale-Improvement (CGI-I) Scores | CGI-I is a global rating scale that measures disease improvement. Using a 7-point scale, the clinician rates how much the subject's illness has improved or worsened relative to the baseline status (1= very much improved; 7= very much worse). | 8 weeks | 
| Clinical Global Impressions Scale-Severity of Illness (CGI-S) Scores | CGI-S is a global rating scale that measures the severity of a subject'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 subjects who have the same diagnosis (1= normal, not at all ill; 7= among the most extremely ill). | 8 weeks | 
| Montgomery and Asberg Depression Rating Scale (MADRS) Total Score Mean Change From Baseline | 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). | Baseline and 8 weeks | 
| Visual Analog Scale-pain Intensity (VAS-PI) Score Mean Change From Baseline | The VAS-PI is a self-rated visual analog scale for the assessment of pain. Scores on the VAS-PI range from 0 (no pain) to 10 (worst possible pain). A decrease in VAS-PI overall scores indicates a subject's assessment of an improvement in pain. | 8 weeks | 
| Hamilton Rating Scale for Depression, 6-item (HAM-D6) Score Mean Change From Baseline | HAM-D6: standardized, clinician-administered rating scale is a subset of the HAM-D17 that assesses 6 items associated with major depression. The scale uses HAM-D17 items 1, 2, 7, 8, 10 and 13. Item 13 is scored 0 to 2 (0=none/absent to 2=most severe) and all others are scored 0 to 4 (0=none/absent to 4=most severe). Total score ranges from 0 to 22; higher score indicates more depression. | 8 weeks | 
| Covi Anxiety Scale Score Mean Change From Baseline | Covi anxiety scale measures the severity of anxiety symptoms on 3 items: verbal report, behavior and somatic complaints. Each dimension is assessed using a 5-point scale: 1 = not at all, 2 = somewhat, 3 = moderately, 4 = considerably, 5 = Very much. Total score ranges from 3 to 15; higher score indicates more anxiety. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
major depressive disorder, MDD, depression