Study Evaluating Desvenlafaxine Succinate Sustained-Release (DVS SR) in Adult Outpatients With Major Depressive Disorder (MDD)

Study Overview
=================
Brief Summary
-----------------
A multicenter, 8-week study to evaluate the efficacy of 2 doses (50 and 100 mg/day) of desvenlafaxine succinate sustained-release (DVS SR) versus placebo in adult outpatients with major depressive disorder.

Official Title
-----------------
A Phase IV, Multicenter, Randomized, 8-Week, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy of 2 Fixed Doses (50 and 100 mg/Day) of Desvenlafaxine Succinate Sustained-Release (DVS SR) in Adult Outpatients With Major Depressive Disorder

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

Intervention / Treatment
-----------------
* Drug: desvenlafaxine succinate sustained-release 50 mg/day
* Drug: desvenlafaxine succinate sustained-release 100 mg/day
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female outpatients aged 18 years or older who are fluent in written and spoken English. A primary diagnosis of MDD based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM- IV-TR), single or recurrent episode, without psychotic features. A HAM-D17 total score ≥20 at the screening and baseline (study day -1) visits and no more than a 4-point improvement from screening to baseline. Exclusion Criteria: Significant risk of suicide based on clinical judgment. Current (within 12 months before baseline) psychoactive substance abuse or dependence (including alcohol), manic episode, posttraumatic stress disorder, obsessive compulsive disorder, or a lifetime diagnosis of bipolar or psychotic disorder. Current generalized anxiety disorder, panic disorder, or social anxiety disorder. History or current evidence of gastrointestinal disease known to interfere with the absorption or excretion of drugs or a history of surgery known to interfere with the absorption or excretion of drugs. Any unstable hepatic, renal, pulmonary, cardiovascular, ophthalmologic, neurologic, or other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: desvenlafaxine succinate sustained-release 50 mg/day<br> | Drug: desvenlafaxine succinate sustained-release 50 mg/day<br>* 50 mg tablets of DVS SR taken orally once daily for 8 weeks; 1 week of placebo taper<br>* Other names: Pristiq;|
| Experimental: desvenlafaxine succinate sustained-release 100 mg/day<br> | Drug: desvenlafaxine succinate sustained-release 100 mg/day<br>* 100 mg tablets of DVS SR taken orally once daily for 8 weeks (which includes 1 week of titration at 50 mg/day); 1 week of taper at 50 mg/day<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* 50 mg and 100 mg placebo matching tablets taken orally once daily for 8 weeks; 1 week of placebo taper<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Hamilton Rating Scale for Depression, 17-item Total Score (HAM-D17) at Week 8 | HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, and weight loss). Each item is scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), for a maximum total score of 52; higher scores indicate more depression. Change from baseline: score at observation minus score at baseline. | Baseline to Week 8 (final on-therapy) | 
| Change From Baseline on the Hamilton Rating Scale for Depression, 17-item Total Score (HAM-D17) at Week 8 | HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, and weight loss). Each item is scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), for a maximum total score of 52; higher scores indicate more depression. Change from baseline: score at observation minus score at baseline | Baseline to Week 8 (final on-therapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Clinical Global Impression Scale-Improvement (CGI-I) | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Higher score = worse outcome. | Baseline to Week 8 (final on-therapy) | 
| Change From Baseline on the Clinical Global Impression-Severity Score (CGI-S) | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = worse state. | Baseline to Week 8 (final on-therapy) | 
| Change From Baseline on the Clinical Global Impression-Severity (CGI-S) Score | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = worse state. | Baseline to Week 8 (final on-therapy) | 
| Hamilton Rating Scale for Depression, 17-item (HAM-D17) Response Rate | HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, and weight loss). Each item is scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), for a maximum total score of 52; higher scores indicate more depression. A response is defined as ≥ 50% decrease from baseline on Hamilton Psychiatric Rating Scale for Depression (HAM-D17) total score. | Baseline to Week 8 (final on-therapy) | 
| Hamilton Rating Scale for Depression, 17-item (HAM-D17) Remission Rate | HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, and weight loss). Each item is scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), for a maximum total score of 52; higher scores indicate more depression. Remission is defined as a Hamilton Psychiatric Rating Scale for Depression (HAM-D17) total score of ≤ 7. | Baseline to week 8 (final on-therapy) | 
| Change From Baseline on the Arizona Sexual Experiences (ASEX) Scale Total Score | The ASEX scale has 5 items to assess sexual functioning with a 1-week recall period. The 5 items assess sex drive, ease of arousal, ease of erection/lubrication, ease of orgasm and orgasm satisfaction. Subjects were encouraged to complete all 5 items regardless of sexual activity during the past week. However, all analyses utilized only the data for the visits where the presence of sexual activity was indicated. Each individual score ranged from 1 to 6; the total score (based on the sum of the individual items) ranged from 5 to 30; higher scores indicated worse sexual function. | Baseline to Week 8 (final on-therapy) |