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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00887224
First received: April 22, 2009
Last updated: November 6, 2014
Last verified: May 2012
Results First Received: March 6, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: Desvenlafaxine succinate sustained release 50 mg
Drug: Desvenlafaxine succinate sustained release 25 mg
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1072 participants were screened, 874 were enrolled into Desvenlafaxine succinate sustained release (DVS SR) open-label 8-week response phase; 659 entered into 12-week open label stability phase. After 20 weeks of open-label treatment 548 subjects were randomized to the 6-month double-blind phase to receive either placebo or to continue with DVS SR.

Reporting Groups
  Description
DVS SR 50 mg (Open-label Phase) Desvenlafaxine succinate sustained release (DVS SR) 50 milligrams (mg) by mouth (PO) once daily (QD) for 20 weeks (Days 1 to 140). This included an 8-week response phase and for responders at Week 8, a 12-week stability phase. Participants who concluded open-label study or discontinued treatment received DVS SR 25 mg PO QD for 7-day taper period (All Enrolled Population).
Placebo (Double-blind Phase) Placebo matching DVS SR 50 mg and DVS SR 25 mg PO QD Days 141 to 147, then placebo matching DVS SR 50 mg PO QD Days 148 to 322 followed by 7-day taper period with placebo matching DVS SR 25 mg PO QD (All Randomized Population).
DVS SR 50 mg (Double-blind Phase) DVS SR 50 mg and placebo matching DVS SR 25 mg PO QD Days 141 to 147; DVS SR 50 mg PO QD Days 148 to 322 followed by 7-day taper period with DVS SR 25 mg PO QD (All Randomized Population).

Participant Flow for 7 periods

Period 1:   Open-label Response (OLR) Phase
    DVS SR 50 mg (Open-label Phase)   Placebo (Double-blind Phase)   DVS SR 50 mg (Double-blind Phase)
STARTED   874   0   0 
COMPLETED   752   0   0 
NOT COMPLETED   122   0   0 
Adverse Event                46                0                0 
Failed to return                6                0                0 
Lack of Efficacy                26                0                0 
Lost to Follow-up                16                0                0 
Unspecified                1                0                0 
Protocol Violation                12                0                0 
Withdrawal by Subject                15                0                0 

Period 2:   Between OLR and OLS Phases
    DVS SR 50 mg (Open-label Phase)   Placebo (Double-blind Phase)   DVS SR 50 mg (Double-blind Phase)
STARTED   752   0   0 
COMPLETED   659   0   0 
NOT COMPLETED   93   0   0 

Period 3:   Open-label Stability (OLS) Phase
    DVS SR 50 mg (Open-label Phase)   Placebo (Double-blind Phase)   DVS SR 50 mg (Double-blind Phase)
STARTED   659   0   0 
COMPLETED   576   0   0 
NOT COMPLETED   83   0   0 
Adverse Event                22                0                0 
Failed to return                3                0                0 
Lack of Efficacy                16                0                0 
Lost to Follow-up                9                0                0 
Unspecified                1                0                0 
Protocol Violation                13                0                0 
Withdrawal by Subject                19                0                0 

Period 4:   Between OLS and DB Phases
    DVS SR 50 mg (Open-label Phase)   Placebo (Double-blind Phase)   DVS SR 50 mg (Double-blind Phase)
STARTED   576   0   0 
COMPLETED   548   0   0 
NOT COMPLETED   28   0   0 

Period 5:   OL Taper Phase / OL Follow Up
    DVS SR 50 mg (Open-label Phase)   Placebo (Double-blind Phase)   DVS SR 50 mg (Double-blind Phase)
STARTED   307 [1]   0   0 
Discontinued Open-label Taper   144 [2]   0   0 
COMPLETED   163   0   0 
NOT COMPLETED   144   0   0 
Adverse Event                28                0                0 
Failed to return                17                0                0 
Physician Decision                10                0                0 
Lost to Follow-up                8                0                0 
Unspecified                30                0                0 
Protocol Violation                3                0                0 
Withdrawal by Subject                48                0                0 
[1] Could have entered 7-day taper period at any time during either the OLR phase or OLS phase.
[2] Could have discontinued at any time during OL taper phase or OL Follow-up (7 days after last dose).

Period 6:   Double-blind (DB) Phase
    DVS SR 50 mg (Open-label Phase)   Placebo (Double-blind Phase)   DVS SR 50 mg (Double-blind Phase)
STARTED   0   276 [1]   272 
COMPLETED   0   176   210 
NOT COMPLETED   0   100   62 
Adverse Event                0                7                2 
Failed to return                0                2                2 
Lack of Efficacy                0                67                33 
Lost to Follow-up                0                8                8 
Unspecified                0                2                0 
Protocol Violation                0                8                5 
Withdrawal by Subject                0                6                12 
[1] 2 participants randomized in error to DB, then entered OL Taper; counted in OL Taper and DB phases.

Period 7:   DB Taper Phase / Post Study Follow Up
    DVS SR 50 mg (Open-label Phase)   Placebo (Double-blind Phase)   DVS SR 50 mg (Double-blind Phase)
STARTED   0   267 [1]   265 
Did Not Enter DB Taper   0   9   7 
Discontinued DB Taper   0   41 [2]   30 
COMPLETED   0   226   235 
NOT COMPLETED   0   41   30 
Adverse Event                0                5                0 
Failed to return                0                5                4 
Physician Decision                0                6                0 
Lost to Follow-up                0                2                2 
Unspecified                0                11                12 
Protocol Violation                0                4                1 
Withdrawal by Subject                0                8                11 
[1] Double-blind participants (DBp) could have entered 7-day taper period at any time during DB phase.
[2] DBp could have discontinued at anytime during DB taper period or Follow-up (7 days after last dose).



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
DVS SR 50 mg (Open-label Phase) DVS SR 50 mg PO QD for 20 weeks (Days 1 to 140). This included an 8-week response phase and for responders at Week 8, a 12-week stability phase. Participants who concluded open-label study or discontinued treatment received DVS SR 25 mg PO QD for 7-day taper period (All Enrolled Population).
Placebo (Double-blind Phase)

Eligible participants from OL Phase were randomized in a 1:1 ratio to either Placebo or DVS SR in the DB Phase.

Placebo matching DVS SR 50 mg and DVS SR 25 mg PO QD Days 141 to 147, then placebo matching DVS SR 50 mg PO QD Days 148 to 322 followed by 7-day taper period with placebo matching DVS SR 25 mg PO QD (All Randomized Population).

DVS SR 50 mg (Double-blind Phase)

Eligible participants from OL Phase were randomized in a 1:1 ratio to either Placebo or DVS SR in the DB Phase.

DVS SR 50 mg and placebo matching DVS SR 25 mg PO QD Days 141 to 147; DVS SR 50 mg PO QD Days 148 to 322 followed by 7-day taper period with DVS SR 25 mg PO QD (All Randomized Population).

Total Total of all reporting groups

Baseline Measures
   DVS SR 50 mg (Open-label Phase)   Placebo (Double-blind Phase)   DVS SR 50 mg (Double-blind Phase)   Total 
Overall Participants Analyzed 
[Units: Participants]
 874   276   272   1422 
Age [1] [2] 
[Units: Years]
Mean (Standard Deviation)
 44.98  (13.25)   NA [2]   NA [2]   44.98  (13.25) 
[1] OL Baseline All Enrolled Population
[2] Baseline Age reported for participants entering the Open-label phase at study start.
Gender [1] 
[Units: Participants]
       
Female   608   0   0   608 
Male   266   0   0   266 
[1] OL Baseline All Enrolled Population. Baseline Gender reported for participants entering the Open-label phase at study start.
Number of participants per categorical score on Clinical Global Impression-Improvement (CGI-I) scale [1] 
[Units: Participants]
       
1=very much improved   0   239   223   462 
2=much improved   0   36   49   85 
3=minimally improved   0   1   0   1 
4=no change   0   0   0   0 
5=minimally worse   0   0   0   0 
6=much worse   0   0   0   0 
7=very much worse   0   0   0   0 
[1] 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. Outcome measure CGI-I results reported for DB phase; CGI-I baseline=DB baseline.
Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Total Score [1] [2] 
[Units: Scores on a scale]
Mean (Standard Deviation)
 NA [2]   4.58  (3.02)   4.69  (2.97)   4.64  (2.99) 
[1] 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.
[2] Outcome measure HAM-D17 results reported for DB phase; HAM-D17 baseline=DB baseline.
Number of participants with remission based on HAM-D17 score [1] 
[Units: Participants]
       
Remission=No   0   46   52   98 
Remission=Yes   0   230   220   450 
[1] HAM-D17: standardized, clinician-administered rating scale that assesses 17 items associated with major depression (such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, and weight loss). Nine items scored on 3 point scale (0=none/absent to 2=most severe) and 8 items scored on 5 point scale (0=none/absent to 4=most severe) for maximum total score of 50; higher score indicates more depression. Remission (Yes or No) based on HAMD-17 total score ≤7. Outcome measure HAM-D17 Remission results reported for DB phase; HAM-D17 Remission baseline=DB baseline.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to Relapse Following Randomization to the Double-blind (DB) Phase: Estimated Probability (Percent) of Relapse at DB Day 185   [ Time Frame: Double-blind phase Baseline (Study Day 140) up to DB Day 185 (Study Day 325) ]

2.  Secondary:   Number of Participants Per Categorical Score for Change From Baseline on Clinical Global Impression-Improvement (CGI-I) Scale   [ Time Frame: Double-blind phase Baseline (Study Day 140) up to Week 26 (Study Day 322) ]

3.  Secondary:   Change From Baseline in Clinical Global Impression-Severity of Illness [CGI-S] Score in the Double-blind Phase   [ Time Frame: Double-blind phase Baseline (Study Day 140) up to Week 26 (Study Day 322) ]

4.  Secondary:   Change From Baseline in Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score in the Double-blind Phase   [ Time Frame: Double-blind phase Baseline (Study Day 140) up to Week 26 (Study Day 322) ]

5.  Secondary:   Change From Baseline in Hamilton Psychiatric Scale for Depression-6 Item (HAM-D6) Score in the Double-blind Phase   [ Time Frame: Double-blind phase Baseline (Study Day 140) up to Week 26 (Study Day 322) ]

6.  Secondary:   Number of Participants With Remission Based on Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Score at Double-blind Phase Week 26   [ Time Frame: Double-blind phase Week 26 (Study Day 322) ]

7.  Secondary:   Change From Baseline of Double-blind Phase in World Health Organization (Five-Item) Well-Being Index   [ Time Frame: Double-blind phase Baseline (Study Day 140), Week 14 (Study Day 238), Week 26 (Study Day 322) ]

8.  Secondary:   Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Score in the Double-blind Phase   [ Time Frame: Double-blind phase Baseline (Study Day 140), Week 14 (Study Day 238), Week 26 (Study Day 322) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
P-value from the primary analysis is different from the one testing equality of relapse rates on Double-blind day 185. Estimated percentages were provided as representative descriptive measures. Medians were not estimable due to low relapse rates.


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00887224     History of Changes
Other Study ID Numbers: 3151A1-3360
B2061004
Study First Received: April 22, 2009
Results First Received: March 6, 2012
Last Updated: November 6, 2014
Health Authority: United States: Food and Drug Administration