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: May 22, 2012

Last verified: May 2012

History of Changes

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
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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

	Placebo (Double-blind Phase)	DVS SR 50 mg (Double-blind Phase)
STARTED	276 ^[1]	272
COMPLETED	176	210
NOT COMPLETED	100	62
Adverse Event	7	2
Failed to return	2	2
Lack of Efficacy	67	33
Lost to Follow-up	8	8
Unspecified	2	0
Protocol Violation	8	5
Withdrawal by Subject	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

	Placebo (Double-blind Phase)	DVS SR 50 mg (Double-blind Phase)
STARTED	267 ^[1]	265
Did Not Enter DB Taper	9	7
Discontinued DB Taper	41 ^[2]	30
COMPLETED	226	235
NOT COMPLETED	41	30
Adverse Event	5	0
Failed to return	5	4
Physician Decision	6	0
Lost to Follow-up	2	2
Unspecified	11	12
Protocol Violation	4	1
Withdrawal by Subject	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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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
Number of Participants [units: participants]	874	276	272	1422
Age ^[1] [units: years] Mean ± Standard Deviation	44.98 ± 13.25	NA ± NA ^[2]	NA ± NA ^[2]	44.98 ± 13.25
Gender ^[3] [units: participants]
Female	608	0	0	608
Male	266	0	0	266
Number of participants per categorical score on Clinical Global Impression-Improvement (CGI-I) scale ^[4] [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
Hamilton Psychiatric Scale for Depression-17 Item (HAM-D17) Total Score ^[5] [units: scores on a scale] Mean ± Standard Deviation	NA ± NA ^[6]	4.58 ± 3.02	4.69 ± 2.97	4.64 ± 2.99
Number of participants with remission based on HAM-D17 score ^[7] [units: participants]
Remission=No	0	46	52	98
Remission=Yes	0	230	220	450

[1]	OL Baseline All Enrolled Population
[2]	Baseline Age reported for participants entering the Open-label phase at study start.
[3]	OL Baseline All Enrolled Population. Baseline Gender reported for participants entering the Open-label phase at study start.
[4]	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.
[5]	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.
[6]	Outcome measure HAM-D17 results reported for DB phase; HAM-D17 baseline=DB baseline.
[7]	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

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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) ]

Show Outcome Measure 1

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) ]

Show Outcome Measure 2

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) ]

Show Outcome Measure 3

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) ]

Show Outcome Measure 4

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) ]

Show Outcome Measure 5

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) ]

Show Outcome Measure 6

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) ]

Show Outcome Measure 7

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) ]

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

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.

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

No publications provided by Pfizer

Publications automatically indexed to this study:

Rosenthal JZ, Boyer P, Vialet C, Hwang E, Tourian KA. Efficacy and safety of desvenlafaxine 50 mg/d for prevention of relapse in major depressive disorder:a randomized controlled trial. J Clin Psychiatry. 2013 Feb;74(2):158-66. doi: 10.4088/JCP.12m07974.

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:	May 22, 2012
Health Authority:	United States: Food and Drug Administration

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