Relapse Prevention Study Of Desvenlafaxine Succinate Sustained Release In Outpatients With Major Depressive Disorder

Study Overview
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Brief Summary
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The primary purpose of this study is to compare the long-term efficacy and safety of desvenlafaxine succinate sustained release versus placebo in adults with Major Depressive Disorder, using a randomized withdrawal design. Randomized withdrawal means that after receiving desvenlafaxine succinate sustained release for a predetermined period of time, subjects will be selected by chance to either continue receiving the study drug or to be withdrawn from the study drug and receive placebo for the remainder of their participation in the trial. Subjects will not know to which group they have been assigned. The study consists of an up to 14-day screening period followed by an 8-week open-label period in which subjects will knowingly receive 50 mg/day of desvenlafaxine succinate sustained release. Subjects who do not respond to treatment, demonstrating no significant change in their depressive symptoms, will be withdrawn from participation at the end of this period. Responding subjects will receive an additional 3 months of open-label desvenlafaxine succinate sustained release at the same dose. Subjects with stable response to treatment at the conclusion of this 3 month period will be randomized to either desvenlafaxine succinate sustained release at 50 mg/day or placebo in a blinded manner for an additional 6 months or until symptoms of depression return. Following discontinuation at any point after enrollment in the study, subjects will receive two weeks of follow-up monitoring, including one week of blinded taper with 25 mg/day of desvenlafaxine succinate sustained release treatment for any subjects who have been taking desvenlafaxine succinate sustained release prior to discontinuation. Subjects assigned to placebo will receive a blinded placebo taper. Following taper, subjects will be evaluated for one additional week to monitor safety.

Official Title
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A Multicenter, Double-Blind, Placebo-Controlled, Randomized Withdrawal, Parallel Group Study To Evaluate The Efficacy And Safety Of 50 mg/Day Of DVS SR In Adult Outpatients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Desvenlafaxine succinate sustained release 50 mg
* Drug: Desvenlafaxine succinate sustained release 25 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult, outpatient with primary diagnosis of Major Depressive Disorder (depressive symptoms for at least 30 days prior to screening) Hamilton Psychiatric Rating Scale for Depression (HAM-D 17) total score of >= 20 Clinical Global Impressions Scale-Severity (CGI-S) score of >= 4. Exclusion Criteria: Significant risk of suicide as assessed by clinician judgment, HAM-D17 and Columbia Suicide-Severity Rating Scale scores. Past treatment with desvenlafaxine succinate sustained release. Other eligibility criteria also apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Desvenlafaxine succinate sustained release 50 mg<br> | Drug: Desvenlafaxine succinate sustained release 50 mg<br>* 50 mg tablet, once daily. 5 months open-label duration for all enrolled subjects; additional 6 months double-blind duration for randomized subjects assigned to this arm.<br>* Other names: Pristiq;Drug: Desvenlafaxine succinate sustained release 25 mg<br>* 25 mg tablet for taper, once daily for 1 week<br>* Other names: Pristiq;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo tablet, once daily. 6 months double-blind duration for randomized subjects assigned to placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Relapse Following Randomization to the Double-blind (DB) Phase: Estimated Probability (Percent) of Relapse at DB Day 185 | Time to relapse analyzed using log-rank test; defined as Hamilton Psychiatric Scale for Depression-17 item score ≥16 at any time during DB phase, discontinuation for unsatisfactory response or efficacy (need for additional or alternate treatment for depression, investigator decision to remove participant for efficacy reasons, or failure to return if investigator determined related to efficacy), hospitalization for depression, suicide attempt, or suicide. Participants who relapsed after DB day 185 or completed DB therapy without relapse were considered as censored on DB day 185 (study day 325). | Double-blind phase Baseline (Study Day 140) up to DB Day 185 (Study Day 325) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Per Categorical Score for Change From Baseline on Clinical Global Impression-Improvement (CGI-I) Scale | CGI-I is a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. | Double-blind phase Baseline (Study Day 140) up to Week 26 (Study Day 322) | 
| Change From Baseline in Clinical Global Impression-Severity of Illness [CGI-S] Score in the Double-blind Phase | CGI-S is a 7-point clinician rated scale to assess severity of participant's current illness state; range of 1 (normal - not ill at all) to 7 (among the most extremely ill). Higher score = more affected. Change from baseline mean=adjusted mean change calculated using mixed-effects model for repeated measures (MMRM). | Double-blind phase Baseline (Study Day 140) up to Week 26 (Study Day 322) | 
| Change From Baseline in Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score in the Double-blind Phase | 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). Nine items are scored on a 3 point scale (0=none/absent to 2=most severe) and 8 items are scored on a 5 point scale (0=none/absent to 4=most severe) for a maximum total score of 50; higher score indicates more depression. Change from baseline mean=adjusted mean change calculated using MMRM. | Double-blind phase Baseline (Study Day 140) up to Week 26 (Study Day 322) | 
| Change From Baseline in Hamilton Psychiatric Scale for Depression-6 Item (HAM-D6) Score in the Double-blind Phase | HAM-D6 is a 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. Change from baseline mean=adjusted mean change calculated using MMRM. | Double-blind phase Baseline (Study Day 140) up to Week 26 (Study Day 322) | 
| Number of Participants With Remission Based on Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score at Double-blind Phase Week 26 | 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). Nine items are scored on a 3 point scale (0=none/absent to 2=most severe) and 8 items are scored on a 5 point scale (0=none/absent to 4=most severe) for a maximum total score of 50; higher score indicates more depression. Remission defined as HAM-D17 total score ≤7. | Double-blind phase Week 26 (Study Day 322) | 
| Change From Baseline of Double-blind Phase in World Health Organization (Five-Item) Well-Being Index | WHO-5 evaluates positive psychological well-being during the past 2 weeks and consists of 5 questions (felt cheerful, in good spirits; felt calm, relaxed; felt active, vigorous; woke up fresh, rested; and daily life filled with things that are interesting) each rated on a 6-point Likert scale from 0 (not present) to 5 (constantly present). Total raw score ranged from 0 (worst possible quality of life) to 25 (best possible quality of life). Change from baseline mean=adjusted mean change calculated using MMRM. | Double-blind phase Baseline (Study Day 140), Week 14 (Study Day 238), Week 26 (Study Day 322) | 
| Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Score in the Double-blind Phase | WPAI is a 6 question participant rated questionnaire to determine the degree to which depression affected work productivity while at work and affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combined absenteeism and presenteeism and percentage of impairment in activities performed outside of work. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher score indicated greater impairment and less productivity. | Double-blind phase Baseline (Study Day 140), Week 14 (Study Day 238), Week 26 (Study Day 322) | 

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