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Trial record 55 of 89 for:    DESVENLAFAXINE

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

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ClinicalTrials.gov Identifier: NCT01056289
Recruitment Status : Completed
First Posted : January 26, 2010
Results First Posted : February 17, 2012
Last Update Posted : February 28, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Desvenlafaxine Succinate Sustained-Release Formulation 50 mg
Drug: Desvenlafaxine Succinate Sustained-Release Formulation 25 mg
Drug: Placebo
Enrollment 480
Recruitment Details  
Pre-assignment Details Eligible participants entered a 24 Week Open-label treatment phase; participants who completed the Open-label phase were randomized to a 4 Week Double-blind treatment phase.
Arm/Group Title DVS SR 50 mg (Open-label Phase) DVS SR 50 mg (Double-blind Phase) DVS SR 25 mg (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description Desvenlafaxine Succinate Sustained-Release Formulation (DVS SR) 50 milligrams (mg) by mouth (PO) once daily (QD) for 24 Weeks. DVS SR 50 mg (reference group): 2 tablets PO once daily (QD) for 1 week (1 tablet DVS SR 50 mg and 1 tablet placebo 25 mg) then DVS SR 50 mg 1 tablet PO QD Weeks 2 through 4. DVS SR 25 mg (taper group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet DVS SR 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4. Placebo (abrupt-discontinuation group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet placebo 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4.
Period Title: Open-label Phase
Started 480 0 0 0
Completed 361 [1] 0 0 0
Not Completed 119 0 0 0
Reason Not Completed
Adverse Event             29             0             0             0
Lost to Follow-up             30             0             0             0
Other             9             0             0             0
Protocol Violation             6             0             0             0
Withdrawal by Subject             26             0             0             0
Lack of Efficacy             18             0             0             0
Not randomized to Double-blind phase             1             0             0             0
[1]
Participants transitioned to Double-blind phase
Period Title: Double-blind Phase
Started 0 73 140 148
Completed 0 69 127 138
Not Completed 0 4 13 10
Reason Not Completed
Adverse Event             0             1             2             1
Lost to Follow-up             0             2             2             2
Other             0             0             1             2
Protocol Violation             0             0             1             1
Withdrawal by Subject             0             0             4             2
Discontinuation symptom             0             1             2             2
Physician Decision             0             0             1             0
Arm/Group Title Entire Study Population
Hide Arm/Group Description 24 Week Open-label phase DVS SR 50 mg PO QD followed by 4 Week Double-blind phase: DVS SR 50 mg (reference group), DVS SR 25 mg (taper group), or Placebo (abrupt-discontinuation group).
Overall Number of Baseline Participants 480
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 480 participants
46.5  (13.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 480 participants
Female
330
  68.8%
Male
150
  31.3%
1.Primary Outcome
Title Total Discontinuation - Emergent Signs and Symptoms (DESS) Score Over the First 2 Weeks of the Double-blind Phase
Hide Description 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).
Time Frame Double-blind phase: Week 1 (Study Day 175), Week 2 (Study Day 182)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): all randomized participants who had at least 1 postrandomization DESS record. Mean was adjusted for baseline DESS score and study center.
Arm/Group Title DVS SR 50 mg DVS SR 25 mg Placebo
Hide Arm/Group Description:
DVS SR 50 mg (reference group): 2 tablets PO once daily (QD) for 1 week (1 tablet DVS SR 50 mg and 1 tablet placebo 25 mg) then DVS SR 50 mg 1 tablet PO QD Weeks 2 through 4.
DVS SR 25 mg (taper group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet DVS SR 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4.
Placebo (abrupt-discontinuation group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet placebo 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4.
Overall Number of Participants Analyzed 72 139 146
Mean (Standard Error)
Unit of Measure: scores on a scale
4.1  (0.72) 4.8  (0.54) 5.3  (0.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DVS SR 50 mg, Placebo
Comments Difference: Placebo versus DVS SR 50 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Null hypothesis: absolute difference between the 2 discontinuation regimens in DESS total scores was >2.5. Alternative hypothesis: absolute difference was ≤2.5; tested by calculating 95% 2-sided confidence intervals (CIs) on the mean difference between the 2 regimens. If absolute values of both confidence limits were ≤2.5, then the regimens were declared equivalent.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
-0.51 to 2.83
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DVS SR 50 mg, DVS SR 25 mg
Comments Difference: DVS SR 25 mg versus DVS SR 50 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Null hypothesis: absolute difference between the 2 discontinuation regimens in DESS total scores was >2.5. Alternative hypothesis: absolute difference was ≤2.5; tested by calculating 95% 2-sided confidence intervals (CIs) on the mean difference between the 2 regimens. If absolute values of both confidence limits were ≤2.5, then the regimens were declared equivalent.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
-1.03 to 2.35
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DVS SR 25 mg, Placebo
Comments Difference: Placebo versus DVS SR 25 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments Null hypothesis: absolute difference between the 2 discontinuation regimens in DESS total scores was >2.5. Alternative hypothesis: absolute difference was ≤2.5; tested by calculating 95% 2-sided confidence intervals (CIs) on the mean difference between the 2 regimens. If absolute values of both confidence limits were ≤2.5, then the regimens were declared equivalent.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-0.88 to 1.89
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Taper Adverse Events (AEs) in the Double-blind Phase
Hide Description 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.
Time Frame Double-blind phase: Baseline (Study Day 168) up to Week 4 (Study Day 196)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population (Double-blind phase): all participants who received at least 1 dose of study treatment and were randomized into the Double-blind treatment phase.
Arm/Group Title DVS SR 50 mg DVS SR 25 mg Placebo
Hide Arm/Group Description:
DVS SR 50 mg (reference group): 2 tablets PO once daily (QD) for 1 week (1 tablet DVS SR 50 mg and 1 tablet placebo 25 mg) then DVS SR 50 mg 1 tablet PO QD Weeks 2 through 4.
DVS SR 25 mg (taper group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet DVS SR 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4.
Placebo (abrupt-discontinuation group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet placebo 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4.
Overall Number of Participants Analyzed 73 140 148
Measure Type: Number
Unit of Measure: percentage of participants
35.6 38.6 50.7
3.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Double-blind phase: Baseline (Study Day 168) up to Week 4 (Study Day 196)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title DVS SR 50 mg DVS SR 25 mg (Double-blind Phase) Placebo
Hide Arm/Group Description:
DVS SR 50 mg (reference group): 2 tablets PO once daily (QD) for 1 week (1 tablet DVS SR 50 mg and 1 tablet placebo 25 mg) then DVS SR 50 mg 1 tablet PO QD Weeks 2 through 4.
DVS SR 25 mg (taper group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet DVS SR 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4.
Placebo (abrupt-discontinuation group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet placebo 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4.
Overall Number of Participants Analyzed 72 139 146
Measure Type: Number
Unit of Measure: percentage of participants
1.4 1.4 1.4
Time Frame Events collected from the signing of the informed consent form up to 14 days after the last dose of study treatment
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title DVS SR 50 mg (Open-label Phase) DVS SR 50 mg (Double-blind Phase) DVS SR 25 mg (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description DVS SR 50 mg PO QD for 24 Weeks. DVS SR 50 mg (reference group): 2 tablets PO once daily (QD) for 1 week (1 tablet DVS SR 50 mg and 1 tablet placebo 25 mg) then DVS SR 50 mg 1 tablet PO QD Weeks 2 through 4. DVS SR 25 mg (taper group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet DVS SR 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4. Placebo (abrupt-discontinuation group): 2 tablets PO QD for 1 week (1 tablet placebo 50 mg and 1 tablet placebo 25 mg) then placebo 50 mg 1 tablet PO QD Weeks 2 through 4.
All-Cause Mortality
DVS SR 50 mg (Open-label Phase) DVS SR 50 mg (Double-blind Phase) DVS SR 25 mg (Double-blind Phase) Placebo (Double-blind Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DVS SR 50 mg (Open-label Phase) DVS SR 50 mg (Double-blind Phase) DVS SR 25 mg (Double-blind Phase) Placebo (Double-blind Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/480 (1.04%)   0/73 (0.00%)   0/140 (0.00%)   0/148 (0.00%) 
Cardiac disorders         
Coronary artery disease * 1  1/480 (0.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Metabolism and nutrition disorders         
Dehydration * 1  1/480 (0.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthritis * 1  1/480 (0.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Muscle twitching * 1  1/480 (0.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Psychiatric disorders         
Intentional self-injury * 1  1/480 (0.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Suicidal ideation * 1  1/480 (0.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea * 1  1/480 (0.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DVS SR 50 mg (Open-label Phase) DVS SR 50 mg (Double-blind Phase) DVS SR 25 mg (Double-blind Phase) Placebo (Double-blind Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   197/480 (41.04%)   9/73 (12.33%)   18/140 (12.86%)   33/148 (22.30%) 
Gastrointestinal disorders         
Diarrhoea * 1  25/480 (5.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Dry mouth * 1  28/480 (5.83%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Nausea * 1  64/480 (13.33%)  5/73 (6.85%)  6/140 (4.29%)  9/148 (6.08%) 
General disorders         
Fatigue * 1  24/480 (5.00%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  25/480 (5.21%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
Nervous system disorders         
Dizziness * 1  39/480 (8.13%)  1/73 (1.37%)  8/140 (5.71%)  14/148 (9.46%) 
Headache * 1  52/480 (10.83%)  3/73 (4.11%)  10/140 (7.14%)  20/148 (13.51%) 
Psychiatric disorders         
Insomnia * 1  38/480 (7.92%)  0/73 (0.00%)  0/140 (0.00%)  0/148 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01056289     History of Changes
Other Study ID Numbers: 3151A1-4437
B2061010
First Submitted: January 22, 2010
First Posted: January 26, 2010
Results First Submitted: January 31, 2012
Results First Posted: February 17, 2012
Last Update Posted: February 28, 2012