Trial Outcomes & Findings for Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) Versus Placebo in Peri- and Postmenopausal Women (NCT NCT00369343)

NCT ID: NCT00369343

Last Updated: 2012-05-07

Results Overview

HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50. Change= 8 week adjusted mean HAM-D17 minus baseline adjusted mean HAM-D17

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

381 participants

Primary outcome timeframe

Baseline to 8 weeks

Results posted on

2012-05-07

Participant Flow

Patients were recruited in the United States from September 2006 to September 2007.

Patients were screened over 4 weeks.

Participant milestones

Participant milestones
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Double-blind Phase
STARTED
256
125
Double-blind Phase
COMPLETED
212
109
Double-blind Phase
NOT COMPLETED
44
16
Open-label Phase
STARTED
212
109
Open-label Phase
COMPLETED
155
79
Open-label Phase
NOT COMPLETED
57
30

Reasons for withdrawal

Reasons for withdrawal
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Double-blind Phase
Adverse Event
19
4
Double-blind Phase
Failed to return
2
0
Double-blind Phase
Lost to Follow-up
9
2
Double-blind Phase
Protocol Violation
2
0
Double-blind Phase
Withdrawal by Subject
8
6
Double-blind Phase
Lack of Efficacy
0
4
Double-blind Phase
Protocol deviation
4
0
Open-label Phase
Adverse Event
19
7
Open-label Phase
Failed to return
4
0
Open-label Phase
Physician Decision
2
0
Open-label Phase
Lost to Follow-up
5
3
Open-label Phase
inadvertently reported study completers
3
2
Open-label Phase
Protocol Violation
1
3
Open-label Phase
Withdrawal by Subject
15
6
Open-label Phase
Lack of Efficacy
4
3
Open-label Phase
Lack of continuance tolerability
3
4
Open-label Phase
did not take study drug
1
2

Baseline Characteristics

Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) Versus Placebo in Peri- and Postmenopausal Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=256 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=125 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Total
n=381 Participants
Total of all reporting groups
Age Continuous
52.01 years
STANDARD_DEVIATION 6.50 • n=5 Participants
52.56 years
STANDARD_DEVIATION 7.17 • n=7 Participants
52.19 years
STANDARD_DEVIATION 6.72 • n=5 Participants
Sex: Female, Male
Female
256 Participants
n=5 Participants
125 Participants
n=7 Participants
381 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 8 weeks

Population: Double-blind phase; modified intent to treat population, which included all randomized patients with a baseline HAM-D17 score ≥18, who took ≥1 dose of study drug and had ≥1 post-baseline HAM-D17 evaluation. Mixed model repeated measures (MMRM) modeling included all available observed data for each patient and no missing values were imputed.

HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50. Change= 8 week adjusted mean HAM-D17 minus baseline adjusted mean HAM-D17

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=157 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=81 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Change in Hamilton Psychiatric Rating Scale for Depression (HAM-D17) Score From Baseline to Week 8.
-12.64 units on scale
Standard Error 0.53
-8.33 units on scale
Standard Error 0.74

SECONDARY outcome

Timeframe: 8 weeks

Population: Double-blind phase, modified intent to treat population, which included all randomized patients with a baseline HAM-D17 score ≥18, took ≥1 dose of study drug and had ≥1 post-baseline HAM-D17 evaluation. Missing data handled by last observation carried forward (LOCF).

CGI-I is a global rating scale that measures disease improvement. Using a 7-point scale, the clinician rates how much the patient's illness has improved or worsened relative to the baseline status (1= very much improved; 7= very much worse).

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=186 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=97 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Percentage of Patients With Each Clinical Global Impression Improvement (CGI-I) Score
1 (very much improved)
42.5 percentage of patients
22.7 percentage of patients
Percentage of Patients With Each Clinical Global Impression Improvement (CGI-I) Score
2 (much improved)
25.3 percentage of patients
18.6 percentage of patients
Percentage of Patients With Each Clinical Global Impression Improvement (CGI-I) Score
3 (minimally improved)
16.7 percentage of patients
17.5 percentage of patients
Percentage of Patients With Each Clinical Global Impression Improvement (CGI-I) Score
4 (no change)
13.4 percentage of patients
32.0 percentage of patients
Percentage of Patients With Each Clinical Global Impression Improvement (CGI-I) Score
5 (minimally worse)
1.1 percentage of patients
7.2 percentage of patients
Percentage of Patients With Each Clinical Global Impression Improvement (CGI-I) Score
6 (much worse)
0.5 percentage of patients
2.1 percentage of patients
Percentage of Patients With Each Clinical Global Impression Improvement (CGI-I) Score
7 (very much worse)
0.5 percentage of patients
0.0 percentage of patients

SECONDARY outcome

Timeframe: 8 weeks

Population: Double-blind phase, modified intent to treat population, which included all randomized patients with a baseline HAM-D17 score ≥18, took ≥1 dose of study drug and had ≥1 post-baseline HAM-D17 evaluation. Missing data handled by last observation carried forward (LOCF).

Remission is defined as a Hamilton Psychiatric Rating Scale for Depression (HAM-D17) score of ≤ 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=186 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=98 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Percentage of Patients Achieving Remission
38.2 percentage of patients
22.4 percentage of patients

SECONDARY outcome

Timeframe: 8 weeks

Population: Double-blind phase, modified intent to treat population, which included all randomized patients with a baseline HAM-D17 score ≥18, took ≥1 dose of study drug and had ≥1 post-baseline HAM-D17 evaluation. Missing data handled by last observation carried forward (LOCF).

A response is defined as ≥ 50% decrease from baseline on Hamilton Psychiatric Rating Scale for Depression (HAM-D17) score. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=186 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=98 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Percentage of Patients Achieving Response to Treatment
58.6 percentage of patients
31.6 percentage of patients

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: Double-blind phase; modified intent to treat population, which included all randomized patients with a baseline HAM-D17 score ≥18, took ≥1 dose of study drug and had ≥1 post-baseline HAM-D17 evaluation. Mixed model repeated measures (MMRM) modeling included all available observed data for each patient and no missing values were imputed.

The HAM-A is a standardized, clinician-administered rating scale that assesses 14 items characteristically associated with major anxiety disorders. Items are scaled 0 - 4 (0=none and 4=very severe), with a maximum total score of 56. Change= 8 week adjusted mean HAM-A score minus baseline adjusted mean score.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=158 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=81 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Change in Hamilton Psychiatric Rating Scale for Anxiety (HAM-A) Score From Baseline to Week 8
-8.62 units on scale
Standard Error 0.44
-5.89 units on scale
Standard Error 0.62

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: Double-blind phase; modified intent to treat population, which included all randomized patients with a baseline HAM-D17 score ≥18, took ≥1 dose of study drug and had ≥1 post-baseline HAM-D17 evaluation.

EQ-5D is a standardized, subject-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health). Change=8 week score minus baseline score.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=158 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=81 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Change in Dimension Health State EuroQol (EQ-5D) Score From Baseline to Week 8
0.18 units on scale
Standard Error 0.02
0.06 units on scale
Standard Error 0.02

SECONDARY outcome

Timeframe: open label baseline and 6 months

Population: Open-label phase safety population: All patients who completed the double-blind phase, elected to continue treatment in the open-label phase, and received at least 1 dose of study drug in the open-label phase. One patient did not have a baseline and at least 1 on therapy assessment.

HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total s core of 50. Change= Final Evaluation mean HAM-D17 minus baseline mean HAM-D17.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=207 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=103 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Change in Hamilton Psychiatric Rating Scale for Depression (HAM-D17) Score From Open Label Baseline to 6 Months
-12.52 units on scale
Standard Deviation 7.17
-12.45 units on scale
Standard Deviation 6.85

SECONDARY outcome

Timeframe: 6 months

Population: Open-label phase safety population: All patients who completed the double-blind phase, elected to continue treatment in the open-label phase, and received at least 1 dose of study drug in the open-label phase.

CGI-I is a global rating scale that measures disease improvement. Using a 7-point scale the clinician rates how much the patient's illness has improved or worsened relative to the baseline status (1= very much improved; 7= very much worse)

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=208 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=103 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Clinical Global Impression Improvement (CGI-I) Score
1.55 units on scale
Standard Deviation 1.00
1.56 units on scale
Standard Deviation 0.99

SECONDARY outcome

Timeframe: 6 months

Population: Open-label phase safety population: All patients who completed the double-blind phase, elected to continue treatment in the open-label phase, and received at least 1 dose of study drug in the open-label phase. One patient did not have a baseline and at least 1 on therapy assessment.

Remission is defined as a Hamilton Psychiatric Rating Scale for Depression (HAM-D17) score of ≤ 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total s core of 50.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=207 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=103 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Percentage of Patients Achieving Remission
55.6 percentage of patients
48.5 percentage of patients

SECONDARY outcome

Timeframe: 6 months

Population: Open-label phase safety population: All patients who completed the double-blind phase, elected to continue treatment in the open-label phase, and received at least 1 dose of study drug in the open-label phase. One patient did not have a baseline and at least 1 on therapy assessment.

A responder is defined as a patient with ≥ 50% decrease from baseline on Hamilton Psychiatric Rating Scale for Depression - 17-item (HAM-D17) score. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on a 0 to 2-4 scale (0=none/absent and 4=most severe) with a maximum total score of 50.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=207 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=103 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Percentage of Patients Achieving a Response to Treatment
70.5 percentage of patients responding
66.0 percentage of patients responding

SECONDARY outcome

Timeframe: open label baseline to 6 months

Population: Open-label phase safety population: All patients who completed the double-blind phase, elected to continue treatment in the open-label phase, and received at least 1 dose of study drug in the open-label phase. One patient did not have a baseline and at least 1 on therapy assessment.

The HAM-A is a standardized, clinician-administered rating scale that assesses 14 items characteristically associated with major anxiety disorders. Items are scaled 0 - 4 (0=none and 4=very severe), with a maximum total score of 56. Change= Final Evaluation mean HAM-A score minus baseline mean score.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=207 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=103 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Change in Hamilton Psychiatric Rating Scale for Anxiety (HAM-A) Score From Open Label Baseline to 6 Months
-10.95 units on scale
Standard Deviation 6.90
-10.38 units on scale
Standard Deviation 5.64

SECONDARY outcome

Timeframe: open label baseline to 6 months

Population: Open-label phase safety population: All patients who completed the double-blind phase, elected to continue treatment in the open-label phase, and received at least 1 dose of study drug in the open-label phase. One patient did not have a baseline and at least 1 on therapy assessment.

EQ-5D is a standardized, subject-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health). Change=8 week score minus baseline score.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=208 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=102 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Change in Dimension Health State EuroQol (EQ-5D) Score From Open Label Baseline to 6 Months
0.19 units on scale
Standard Deviation 0.26
0.22 units on scale
Standard Deviation 0.31

SECONDARY outcome

Timeframe: 6 months

Population: Open-label (OL) safety population: Patients completed double-blind and continued in OL with ≥1 dose study drug. Excluded patients lost to follow-up and discontinued with \<4 wks therapy. Patients analyzed varied by time (0mg, 100mg, 200mg): Early Termination (n=9,98,207); Taper week 1 (n=4,76,193); Taper week 2 (n=5,75,195); Post-taper (n=5,71,192)

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom," "absent," or "old symptom but improved" for a total possible range of 0 to 43. A higher score indicates more symptoms.

Outcome measures

Outcome measures
Measure
Desvenlafaxine Succinate Sustained-Release (DVS SR)
n=9 Participants
Double-blind Phase Days 1 to 7: 50 mg/day (one 50 mg tablet) Days 8 to 14: 100 mg/day (one 100 mg tables) Days 15 to 56: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
Placebo
n=98 Participants
Double-blind Phase Placebo administered daily for 8 weeks Open-label Phase Days 57-63: 100 mg/day (one 100 mg tablet) Days 64-238: At the discretion of the investigator, patients assigned 100 mg/day (one 100 mg tablet) or 200 mg/day (two 100 mg tablets) Taper Phase Day 239 or at discontinuation: If patient taking 200 mg/day, then decreased to 100 mg/day for 7 days, and then decreased to 50 mg/day for 7 days. Patients taking 100 mg/day decreased to 50 mg/day for 7 days.
200 mg
n=207 Participants
DVS SR 200mg dosage was reduced to DVS SR 100mg for 7 days and then further reduced to DVS SR 50mg from days 8 to 14.
Discontinuation-Emergent Signs and Symptoms (DESS) Total Score
End of 8 week DB / OL phase or early termination
4.00 units on scale
Standard Deviation 5.05
2.07 units on scale
Standard Deviation 4.03
1.27 units on scale
Standard Deviation 3.40
Discontinuation-Emergent Signs and Symptoms (DESS) Total Score
Taper week 1
2.00 units on scale
Standard Deviation 2.16
3.32 units on scale
Standard Deviation 4.35
2.47 units on scale
Standard Deviation 3.61
Discontinuation-Emergent Signs and Symptoms (DESS) Total Score
Taper week 2
1.40 units on scale
Standard Deviation 3.13
5.29 units on scale
Standard Deviation 5.96
3.76 units on scale
Standard Deviation 4.71
Discontinuation-Emergent Signs and Symptoms (DESS) Total Score
Post-taper
0.60 units on scale
Standard Deviation 0.89
1.41 units on scale
Standard Deviation 2.18
2.46 units on scale
Standard Deviation 3.97

Adverse Events

Double-blind DVS SR

Serious events: 3 serious events
Other events: 217 other events
Deaths: 0 deaths

Double-blind Placebo

Serious events: 2 serious events
Other events: 94 other events
Deaths: 0 deaths

Open-label DVS SR/ DVS SR

Serious events: 12 serious events
Other events: 198 other events
Deaths: 0 deaths

Open-label Placebo/DVS SR

Serious events: 2 serious events
Other events: 97 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Double-blind DVS SR
Days 1 to 7: Patients will be instructed to take 1-50mg tablet per day Days 8 to 14: Patients will be instructed to take 1-100mg tablet per day Days 15 to 56: At the discretion of the investigator, patients may be assigned to 100mg or 200mg tablets per day
Double-blind Placebo
Placebo administered daily for 8 weeks
Open-label DVS SR/ DVS SR
Patients were in the DVS SR arm during both the double-blind and open-label phase.
Open-label Placebo/DVS SR
Patients were in the Placebo arm during the double-blind phase and the DVS SR arm during the open-label phase.
Cardiac disorders
Hypertension
0.39%
1/256
0.00%
0/125
0.00%
0/208
0.00%
0/103
Skin and subcutaneous tissue disorders
Skin carcinoma
0.00%
0/256
0.80%
1/125
0.00%
0/208
0.00%
0/103
Nervous system disorders
Psychotic depression
0.39%
1/256
0.00%
0/125
0.00%
0/208
0.00%
0/103
General disorders
Infection
0.39%
1/256
0.00%
0/125
0.00%
0/208
0.00%
0/103
Cardiac disorders
Cerebrovascular disorder
0.00%
0/256
0.80%
1/125
0.00%
0/208
0.00%
0/103
General disorders
Medication error
0.39%
1/256
0.00%
0/125
0.00%
0/208
0.00%
0/103
General disorders
Chest pain
0.39%
1/256
0.00%
0/125
0.00%
0/208
0.97%
1/103
Reproductive system and breast disorders
Uterine fibroids enlarged
0.00%
0/256
0.00%
0/125
0.00%
0/208
0.97%
1/103
General disorders
Accidental overdose
0.00%
0/256
0.00%
0/125
1.4%
3/208
0.00%
0/103
General disorders
Overdose
0.00%
0/256
0.00%
0/125
0.96%
2/208
0.00%
0/103
General disorders
Allergic reaction
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103
Vascular disorders
Cerebral ischemia
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103
Cardiac disorders
Supraventricular tachycardia
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103
Vascular disorders
Deep vein thrombosis
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103
Blood and lymphatic system disorders
Coagulation disorder
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103
Nervous system disorders
Psychosis
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103
Skin and subcutaneous tissue disorders
Skin melanoma
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103
Reproductive system and breast disorders
Endometrial carcinoma
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103
Reproductive system and breast disorders
Breast carcinoma
0.00%
0/256
0.00%
0/125
0.48%
1/208
0.00%
0/103

Other adverse events

Other adverse events
Measure
Double-blind DVS SR
Days 1 to 7: Patients will be instructed to take 1-50mg tablet per day Days 8 to 14: Patients will be instructed to take 1-100mg tablet per day Days 15 to 56: At the discretion of the investigator, patients may be assigned to 100mg or 200mg tablets per day
Double-blind Placebo
Placebo administered daily for 8 weeks
Open-label DVS SR/ DVS SR
Patients were in the DVS SR arm during both the double-blind and open-label phase.
Open-label Placebo/DVS SR
Patients were in the Placebo arm during the double-blind phase and the DVS SR arm during the open-label phase.
General disorders
Abdominal pain
4.3%
11/256
6.4%
8/125
10.1%
21/208
7.8%
8/103
General disorders
Asthenia
6.6%
17/256
8.0%
10/125
10.1%
21/208
10.7%
11/103
General disorders
Headache
26.6%
68/256
20.8%
26/125
39.4%
82/208
41.7%
43/103
General disorders
Infection
6.2%
16/256
8.0%
10/125
19.2%
40/208
17.5%
18/103
General disorders
Pain
3.1%
8/256
5.6%
7/125
9.6%
20/208
11.7%
12/103
Vascular disorders
Hypertension
6.6%
17/256
1.6%
2/125
10.1%
21/208
3.9%
4/103
Vascular disorders
Vasodilatation
5.9%
15/256
4.0%
5/125
8.7%
18/208
6.8%
7/103
Gastrointestinal disorders
Anorexia
5.9%
15/256
0.80%
1/125
5.8%
12/208
5.8%
6/103
Gastrointestinal disorders
Constipation
14.1%
36/256
6.4%
8/125
17.8%
37/208
21.4%
22/103
Gastrointestinal disorders
Diarrhea
8.6%
22/256
10.4%
13/125
15.9%
33/208
14.6%
15/103
Gastrointestinal disorders
Dry mouth
23.8%
61/256
9.6%
12/125
26.9%
56/208
22.3%
23/103
Gastrointestinal disorders
Dyspepsia
6.2%
16/256
1.6%
2/125
9.6%
20/208
3.9%
4/103
Gastrointestinal disorders
Nausea
16.8%
43/256
12.0%
15/125
25.0%
52/208
31.1%
32/103
Nervous system disorders
Dizziness
11.3%
29/256
7.2%
9/125
2.9%
6/208
5.8%
6/103
Nervous system disorders
Insomnia
11.3%
29/256
6.4%
8/125
15.4%
32/208
15.5%
16/103
Nervous system disorders
Nervousness
5.1%
13/256
3.2%
4/125
6.7%
14/208
6.8%
7/103
Nervous system disorders
Somnolence
14.5%
37/256
7.2%
9/125
13.0%
27/208
14.6%
15/103
Skin and subcutaneous tissue disorders
Sweating
6.6%
17/256
2.4%
3/125
9.6%
20/208
11.7%
12/103
General disorders
Accidental injury
0.00%
0/256
0.00%
0/125
16.8%
35/208
11.7%
12/103
General disorders
Back pain
0.00%
0/256
0.00%
0/125
6.2%
13/208
5.8%
6/103
General disorders
Flu syndrome
0.00%
0/256
0.00%
0/125
5.3%
11/208
4.9%
5/103
Gastrointestinal disorders
Vomiting
0.00%
0/256
0.00%
0/125
3.4%
7/208
8.7%
9/103
Metabolism and nutrition disorders
Weight gain
0.00%
0/256
0.00%
0/125
8.2%
17/208
8.7%
9/103
Musculoskeletal and connective tissue disorders
Arthralgia
0.00%
0/256
0.00%
0/125
8.7%
18/208
5.8%
6/103
Nervous system disorders
Abnormal dreams
0.00%
0/256
0.00%
0/125
7.2%
15/208
0.97%
1/103
Nervous system disorders
Anxiety
0.00%
0/256
0.00%
0/125
2.9%
6/208
5.8%
6/103
Nervous system disorders
Hostility
0.00%
0/256
0.00%
0/125
1.4%
3/208
6.8%
7/103
Respiratory, thoracic and mediastinal disorders
Pharyngitis
0.00%
0/256
0.00%
0/125
5.8%
12/208
9.7%
10/103
Respiratory, thoracic and mediastinal disorders
Rhinitis
0.00%
0/256
0.00%
0/125
6.7%
14/208
6.8%
7/103
Respiratory, thoracic and mediastinal disorders
Sinusitis
0.00%
0/256
0.00%
0/125
11.1%
23/208
10.7%
11/103
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
0.00%
0/256
0.00%
0/125
9.1%
19/208
8.7%
9/103
Eye disorders
Abnormal vision
0.00%
0/256
0.00%
0/125
6.2%
13/208
4.9%
5/103
Ear and labyrinth disorders
Tinnitus
0.00%
0/256
0.00%
0/125
7.2%
15/208
1.9%
2/103

Additional Information

U. S. Contact Center

Wyeth

Results disclosure agreements

  • Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
  • Publication restrictions are in place

Restriction type: OTHER