Study Comparing Discontinuation Symptoms Of DVS SR In Subjects With Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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Study Comparing Discontinuation Symptoms in subjects with Major Depressive Disorder treated for 24 Weeks with Open-label 50 mg Desvenlafaxine Succinate Sustained-Release Formulation (DVS SR)

Official Title
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A Randomized, Double-Blind, Parallel Group Study To Compare Discontinuation Symptoms In Abrupt Discontinuation Versus A 1-Week Tapering Regimen In Subjects With MDD Treated For 24 Weeks With Open-Label 50 mg DVS SR Formulation

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Desvenlafaxine Succinate Sustained-Release Formulation 50 mg
* Drug: Desvenlafaxine Succinate Sustained-Release Formulation 25 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary Diagnosis of Major Depressive Disorder Hamilton Psychiatric Rating Scale for Depression-17-Item score of greater than or equal to 14 at baseline Exclusion Criteria: Current psychoactive substance abuse or dependence, manic episode, or a lifetime diagnosis of bipolar or psychotic disorder Potentially violent to others or is at significant risk for suicide History or current evidence of gastrointestinal disease or history of surgery known to interfere with absorption or excretion Known presence of raised intraocular pressure or history of narrow angle glaucoma

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 |
| --- | --- |
| Active Comparator: Desvenlafaxine Succinate Sustained-Release Formulation 50 mg<br> | Drug: Desvenlafaxine Succinate Sustained-Release Formulation 50 mg<br>* DVS SR 50 mg Reference Group/Arm, oral tablet, 2 tablets/day during the first week and 1 tablet/day during weeks 2 through 4 of the double-blind treatment phase.<br>|
| Active Comparator: Desvenlafaxine Succinate Sustained-Release Formulation 25 mg<br> | Drug: Desvenlafaxine Succinate Sustained-Release Formulation 25 mg<br>* DVS SR 25 mg Taper Group/Arm, oral tablet, 2 tablets/day during the first week and 1 tablet/day during weeks 2 through 4 of the double-blind treatment phase.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* DVS SR Placebo Abrupt Discontinuation Group/Arm, oral tablet, 2 tablets/day during the first week and 1 tablet/day during weeks 2 through 4 of the double-blind treatment phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Discontinuation - Emergent Signs and Symptoms (DESS) Score Over the First 2 Weeks of the Double-blind Phase | Clinician-administered 43-item assessment to evaluate discontinuation-emergent symptoms resulting from withdrawal from study treatment. Total score=sum of number of new symptoms and old (but worse) symptoms (score=1) and old and unchanged symptom, absent, or old symptom but improved (score=0); total possible range 0 to 43. Higher score=more symptoms. New symptom=any symptom that appeared within 7 days before DESS administration; old symptom=any symptom that appeared 7 days before DESS administration and continued into 7-day period. DESS calculated as 2*mean(of DESSDB Week 1, DESSDB Week 2). | Double-blind phase: Week 1 (Study Day 175), Week 2 (Study Day 182) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Taper Adverse Events (AEs) in the Double-blind Phase | Any untoward medical occurrence in a patient who received study drug was considered an AE without regard to possibility of causal relationship. Taper-emergent AEs (TPAEs) are those events which occurred during the double-blind period but did not occur during the last 7 days of the on-therapy period or existed during the last 7 days and worsened in the double-blind period. | Double-blind phase: Baseline (Study Day 168) up to Week 4 (Study Day 196) | 
| Percentage of Participants Who Were Unable to Successfully Complete Tapering of the Study Drug Because of the Number and/or Severity of Their Discontinuation Symptoms | Discontinuation symptoms may occur following abrupt cessation of serotonergic antidepressants in a minority of participants following short-term treatment of an episode of Major Depressive Disorder (MDD). The symptoms include emotional and somatic symptoms such as dizziness, nausea, and paresthesia and typically appear within 2 to 3 days of reducing the dose or stopping the antidepressant medication. Discontinuation symptoms are usually mild and resolve spontaneously within a week in the majority of patients, though a minority can have intense and prolonged symptoms. | Double-blind phase: Baseline (Study Day 168) up to Week 4 (Study Day 196) |