Depressive Disorder, Major
Conditions
Keywords
Major Depressive Disorder
Brief summary
This is a multicenter study to assess the health and well-being in subjects who are outpatients with major depressive disorder that take desvenlafaxine succinate sustained release (DVS SR) or placebo for 12 weeks.
Interventions
50 mg/day oral tablet for 12 weeks
GENETICGenotyping
CYP2D6 genotyping at randomization
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Outpatient men and women, between the ages of 18 to 75 years, fluent in both written and spoken English. * Employed for 20 hours or more for a minimum of 1 month prior to baseline. * Primary diagnosis of Major Depressive Disorder with symptoms for at least 30 days prior to baseline.
Exclusion criteria
* Treatment with desvenlafaxine succinate sustained release at any time in the past and/or venlafaxine (Effexor or Effexor XR) 1 year prior to baseline. * Treatment-resistant defined as any of the following failed treatments in the past 3 years: 3 or more previous adequate trials of \>=2 classes of antidepressant medication, electroconvulsive therapy, or psychotherapy (2 adequate trials). * Current (within 12 months prior to the screening visit) psychoactive substance abuse or dependence (including alcohol), manic episode, posttraumatic stress disorder, obsessive-compulsive disorder, or a lifetime diagnosis of bipolar or psychotic disorder. * Clinically important abnormalities on physical examination, electrocardiogram (ECG), or laboratory evaluations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hamilton Depression Scale (HAM-D) at Week 12 | At Baseline and Week 12. | HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilt feelings, suicide, sleep disturbances, anxiety levels and weight loss). Total score ranges from 0 to 52; higher scores indicate more depression. Change from baseline: mean at observation minus mean at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | At Baseline and Week 12. | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. Change = score at observation minus score at baseline. |
| Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | At Baseline and Week 12. | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Change: score at observation minus score at baseline. |
| Change From Baseline on Work and Activities Item of HAM-D17 at Week 12 | At Baseline and Week 12. | The Work and Activities Item of the HAM-D17 is item 7 of HAM-D17. Scoring range from 0 to 4. |
| Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 12 | At Baseline and Week 12. | Participant rated scale was used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Individual item scores range from 0 to 10. |
| Change From Baseline on Worry Anxiety Tension Scale (WATS) at Week 12 | At Baseline and Week 12. | WATS: a self-administered, 3-question rating scale assesses worry, anxiety, and tension. Each item was a visual analog scale on which the participant circles a number from 0 to 10. Higher scores indicated worse function. WATS total score was the sum of the 3 items. If 1 item was missing, the total score would be missing. |
| Change From Baseline on Stress and Social Support Scales at Week 12 | At Baseline and Week 12. | Stress and Social Support Scales: self-administered rating scale where item 1 is the stress vulnerability scale measuring how much the subject was set back by stressful events on an 11-point scale ranging from 0 (not at all) to 10 (extremely) and item 2 is an 11-point scale ranging from 0 to 100 percent of the amount of support the subject received from relatives and friends. |
| Change From Baseline in Adjusted Mean on Montgomery-Asberg Depression Rating Scale (MADRS) at Week 12 | At Baseline and Week 12. | Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). |
Participant flow
Recruitment details
A total of 752 potential participants were screened for this study. 437 participants were randomized to treatment groups while 315 participants were not randomized (288: did not meet the study criteria; 27 were not randomized for other reasons). Of the 437 randomized participants, 10 participants did not receive the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| DVS SR 50 mg Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food. | 285 |
| Placebo Participants were administered an oral dose of placebo once daily with or without food. | 142 |
| Total | 427 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 6 |
| Overall Study | Discontinuation of Study by Sponsor | 1 | 2 |
| Overall Study | Lack of Efficacy | 7 | 8 |
| Overall Study | Lost to Follow-up | 11 | 9 |
| Overall Study | Non-compliance | 1 | 1 |
| Overall Study | Participant on prohibited medication | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 8 |
Baseline characteristics
| Characteristic | DVS SR 50 mg | Placebo | Total |
|---|---|---|---|
| Age Continuous | 43.16 years STANDARD_DEVIATION 11.72 | 41.57 years STANDARD_DEVIATION 12.64 | 42.63 years STANDARD_DEVIATION 12.04 |
| Sex: Female, Male Female | 188 Participants | 93 Participants | 281 Participants |
| Sex: Female, Male Male | 97 Participants | 49 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 213 / 285 | 90 / 142 |
| serious Total, serious adverse events | 2 / 285 | 2 / 142 |
Outcome results
Primary
Change From Baseline in Hamilton Depression Scale (HAM-D) at Week 12
HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilt feelings, suicide, sleep disturbances, anxiety levels and weight loss). Total score ranges from 0 to 52; higher scores indicate more depression. Change from baseline: mean at observation minus mean at baseline.
Time frame: At Baseline and Week 12.
Population: Intent-to-treat (ITT) analysis set, Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 50 mg | Change From Baseline in Hamilton Depression Scale (HAM-D) at Week 12 | -12.61 Scores on a scale | Standard Error 0.45 |
| Placebo | Change From Baseline in Hamilton Depression Scale (HAM-D) at Week 12 | -10.50 Scores on a scale | Standard Error 0.6 |
p-value: 0.00295% CI: [0.78, 3.46]ANCOVA
Secondary
Change From Baseline in Adjusted Mean on Montgomery-Asberg Depression Rating Scale (MADRS) at Week 12
Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time frame: At Baseline and Week 12.
Population: ITT, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 50 mg | Change From Baseline in Adjusted Mean on Montgomery-Asberg Depression Rating Scale (MADRS) at Week 12 | -18.44 Scores on a scale | Standard Error 0.69 |
| Placebo | Change From Baseline in Adjusted Mean on Montgomery-Asberg Depression Rating Scale (MADRS) at Week 12 | -16.18 Scores on a scale | Standard Error 0.94 |
p-value: 0.03595% CI: [0.16, 4.37]ANCOVA
Secondary
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 12
Participant rated scale was used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Individual item scores range from 0 to 10.
Time frame: At Baseline and Week 12.
Population: ITT, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 50 mg | Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 12 | -9.41 Scores on a scale | Standard Error 0.48 |
| Placebo | Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 12 | -8.08 Scores on a scale | Standard Error 0.63 |
p-value: 0.06795% CI: [-0.09, 2.76]ANCOVA
Secondary
Change From Baseline on Stress and Social Support Scales at Week 12
Stress and Social Support Scales: self-administered rating scale where item 1 is the stress vulnerability scale measuring how much the subject was set back by stressful events on an 11-point scale ranging from 0 (not at all) to 10 (extremely) and item 2 is an 11-point scale ranging from 0 to 100 percent of the amount of support the subject received from relatives and friends.
Time frame: At Baseline and Week 12.
Population: ITT, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 50 mg | Change From Baseline on Stress and Social Support Scales at Week 12 | -2.53 Scores on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline on Stress and Social Support Scales at Week 12 | -2.14 Scores on a scale | Standard Error 0.23 |
p-value: 0.14595% CI: [-0.13, 0.91]ANCOVA
Secondary
Change From Baseline on Work and Activities Item of HAM-D17 at Week 12
The Work and Activities Item of the HAM-D17 is item 7 of HAM-D17. Scoring range from 0 to 4.
Time frame: At Baseline and Week 12.
Population: ITT, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 50 mg | Change From Baseline on Work and Activities Item of HAM-D17 at Week 12 | -1.68 Scores on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline on Work and Activities Item of HAM-D17 at Week 12 | -1.45 Scores on a scale | Standard Error 0.1 |
p-value: 0.0495% CI: [0.01, 0.44]ANCOVA
Secondary
Change From Baseline on Worry Anxiety Tension Scale (WATS) at Week 12
WATS: a self-administered, 3-question rating scale assesses worry, anxiety, and tension. Each item was a visual analog scale on which the participant circles a number from 0 to 10. Higher scores indicated worse function. WATS total score was the sum of the 3 items. If 1 item was missing, the total score would be missing.
Time frame: At Baseline and Week 12.
Population: ITT, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DVS SR 50 mg | Change From Baseline on Worry Anxiety Tension Scale (WATS) at Week 12 | -13.39 Scores on a scale | Standard Error 0.79 |
| Placebo | Change From Baseline on Worry Anxiety Tension Scale (WATS) at Week 12 | -10.95 Scores on a scale | Standard Error 1.04 |
p-value: 0.04195% CI: [0.1, 4.78]ANCOVA
Secondary
Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. Change = score at observation minus score at baseline.
Time frame: At Baseline and Week 12.
Population: ITT, LOCF
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| DVS SR 50 mg | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 3 (Minimally Improved) | 53 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 5 (Minimally Worse) | 10 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 2 (Much Improved) | 84 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 6 (Much Worse) | 0 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 4 (No Change) | 34 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 7 (Very Much Worse) | 1 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 1 (Very Much Improved) | 103 Scores on a scale | 0.07 |
| Placebo | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 7 (Very Much Worse) | 0 Scores on a scale | — |
| Placebo | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 1 (Very Much Improved) | 31 Scores on a scale | 0.1 |
| Placebo | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 2 (Much Improved) | 44 Scores on a scale | — |
| Placebo | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 3 (Minimally Improved) | 31 Scores on a scale | — |
| Placebo | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 4 (No Change) | 30 Scores on a scale | — |
| Placebo | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 5 (Minimally Worse) | 5 Scores on a scale | — |
| Placebo | Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 | 6 (Much Worse) | 1 Scores on a scale | — |
p-value: 0.001Cochran-Mantel-Haenszel
Secondary
Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Change: score at observation minus score at baseline.
Time frame: At Baseline and Week 12.
Population: ITT, LOCF
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| DVS SR 50 mg | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 3 (Minimally Improved) | 77 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 5 (Minimally Worse) | 14 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 2 (Much Improved) | 68 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 6 (Much Worse) | 1 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 4 (No Change) | 56 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 7 (Very Much Worse) | 0 Scores on a scale | — |
| DVS SR 50 mg | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 1 (Very Much Improved) | 69 Scores on a scale | 0.08 |
| Placebo | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 7 (Very Much Worse) | 0 Scores on a scale | — |
| Placebo | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 1 (Very Much Improved) | 23 Scores on a scale | 0.11 |
| Placebo | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 2 (Much Improved) | 30 Scores on a scale | — |
| Placebo | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 3 (Minimally Improved) | 31 Scores on a scale | — |
| Placebo | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 4 (No Change) | 43 Scores on a scale | — |
| Placebo | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 5 (Minimally Worse) | 15 Scores on a scale | — |
| Placebo | Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 | 6 (Much Worse) | 0 Scores on a scale | — |
p-value: 0.002Cochran-Mantel-Haenszel