Major Depressive Disorder
Conditions
Brief summary
A multicenter, 10-week study to evaluate the efficacy and safety of 50 mg of desvenlafaxine succinate sustained-release formulation (DVS SR) versus placebo in the treatment of peri- and postmenopausal women with major depressive disorder
Interventions
50-mg DVS SR tablets taken orally once daily.
DRUGplacebo
Placebo tablets taken orally once daily.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Peri- and postmenopausal women aged 40 to 70 years who are fluent in both written and spoken English. * Postmenopausal status defined by 12 consecutive months of spontaneous amenorrhea; less than 12 consecutive months with at least 6 consecutive months of spontaneous amenorrhea and a pre-baseline follicle-stimulating hormone (FSH) level \>40 mIU/mL; or 6 months postsurgical bilateral oophorectomy (with or without hysterectomy). Perimenopausal women defined by the presence of any of the following within 6 months before baseline: 1. an absolute change of 7 days or more in menstrual cycle length within 6 months before baseline; 2. a change in menstrual flow amount (2 or more flow categories, eg, from light or moderately light to moderately heavy or heavy); 3. a change in duration (absolute change of 2 or more days); or 4. periods of amenorrhea lasting at least 3 months. * A primary diagnosis of major depressive disorder (MDD) based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR), single or recurrent episode, without psychotic features using the modified Mini International Neuropsychiatric Interview (MINI). * A Montgomery and Asberg Depression Rating Scale (MADRS) total score \>=25 at the screening and baseline (day -1) visits and no more than a 5-point improvement from screening to baseline.
Exclusion criteria
* Treatment with DVS SR (Pristiq®) at any time in the past and/or venlafaxine, ie, Effexor® or Effexor XR®, 1 year prior to baseline. * Treatment-resistant; eg, in the past 3 years if any of the following treatments have failed: (a) 3 or more previous adequate trials of \>=2 classes of antidepressant medication, (b) electroconvulsive therapy, or (c) 2 adequate trials of psychotherapy (eg, behavior therapy, behavior-marital therapy). * History or current evidence of gastrointestinal disease known to interfere with the absorption or excretion of drugs or a history of surgery known to interfere with the absorption or excretion of drugs. * Known presence of raised intraocular pressure or history of narrow-angle glaucoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hamilton Depression Scale (HAM-D17) at Week 8 | Baseline, Week 8 | HAM-D17, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, & weight loss). Total score ranges from 0 to 52; higher scores indicate more severe depression. Change from baseline: score at observation minus score at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Week 8 | CGI-I: 7-point scale in which the clinician rated how much the participant's condition has changed compared to baseline. Scores ranged 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. Higher score = more affected. |
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Week 8 | Baseline, Week 8 | 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 in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 8 | Baseline, Week 8 | 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). Change: score at observation minus score at baseline. |
| Change From Baseline in Quick Inventory of Depressive Symptoms, 16 Question Self-report (QIDS-SR) | Baseline, Week 8 | This is a 16-item self reported questionnaire that measures depressive symptoms. Improvement reported as change in depressive score. Score ranges from 0 to 42, with higher numbers indicating more severe symptom reporting. Change: score at observation minus score at baseline. |
| Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Week 8 | Baseline, Week 8 | 10 centimeter (cm) line (Visual Analog Scale) marked by participant. Intensity of pain range (over past week): 0 = no pain to 10 = worst possible pain. Change: score at observation minus score at baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Desvenlafaxine Succinate Desvenlafaxine succinate sustained-release (DVS SR) 50 milligram tablets once daily for 10 weeks | 217 |
| Placebo Matching placebo tablets once daily for 10 weeks | 217 |
| Total | 434 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 5 |
| Overall Study | Discontinuation of study by sponsor | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 11 |
| Overall Study | Lost to Follow-up | 5 | 9 |
| Overall Study | Other | 3 | 3 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Randomized, not treated | 1 | 4 |
| Overall Study | Withdrawal by Subject | 8 | 7 |
Baseline characteristics
| Characteristic | Desvenlafaxine Succinate | Placebo | Total |
|---|---|---|---|
| Age Continuous | 53.1 Years STANDARD_DEVIATION 6.85 | 52.8 Years STANDARD_DEVIATION 6.58 | 53.0 Years STANDARD_DEVIATION 6.71 |
| Sex: Female, Male Female | 217 Participants | 217 Participants | 434 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 100 / 217 | 90 / 217 |
| serious Total, serious adverse events | 2 / 217 | 2 / 217 |
Outcome results
Primary
Change From Baseline in Hamilton Depression Scale (HAM-D17) at Week 8
HAM-D17, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, & weight loss). Total score ranges from 0 to 52; higher scores indicate more severe depression. Change from baseline: score at observation minus score at baseline.
Time frame: Baseline, Week 8
Population: Full Analysis Set (FAS) Population: randomized participants who had a baseline HAM-D17 score, took at least 1 dose of investigational product, and had at least 1 postbaseline HAM-D17 evaluation. Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Desvenlafaxine Succinate | Change From Baseline in Hamilton Depression Scale (HAM-D17) at Week 8 | Baseline | 22.8 Units on a scale | Standard Deviation 3.29 |
| Desvenlafaxine Succinate | Change From Baseline in Hamilton Depression Scale (HAM-D17) at Week 8 | Change at Week 8 | -9.7 Units on a scale | Standard Deviation 6.54 |
| Placebo | Change From Baseline in Hamilton Depression Scale (HAM-D17) at Week 8 | Baseline | 22.4 Units on a scale | Standard Deviation 3.51 |
| Placebo | Change From Baseline in Hamilton Depression Scale (HAM-D17) at Week 8 | Change at Week 8 | -7.4 Units on a scale | Standard Deviation 6.74 |
Comparison: Null hypothesis: no difference between treatment groupsp-value: 0.004ANCOVA
Secondary
Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Week 8
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: Baseline, Week 8
Population: FAS; LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Desvenlafaxine Succinate | Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Week 8 | Baseline | 4.4 Units on a scale | Standard Deviation 0.6 |
| Desvenlafaxine Succinate | Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Week 8 | Change at Week 8 | -1.5 Units on a scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Week 8 | Baseline | 4.3 Units on a scale | Standard Deviation 0.53 |
| Placebo | Change From Baseline in Clinical Global Impression - Severity (CGI-S) at Week 8 | Change at Week 8 | -1.1 Units on a scale | Standard Deviation 1.24 |
p-value: 0.002ANCOVA
Secondary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 8
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). Change: score at observation minus score at baseline.
Time frame: Baseline, Week 8
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Desvenlafaxine Succinate | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 8 | Baseline | 31.0 Units on a scale | Standard Deviation 3.76 |
| Desvenlafaxine Succinate | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 8 | Change at Week 8 | -14.8 Units on a scale | Standard Deviation 9.09 |
| Placebo | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 8 | Baseline | 30.6 Units on a scale | Standard Deviation 3.83 |
| Placebo | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 8 | Change at Week 8 | -11.6 Units on a scale | Standard Deviation 9.99 |
p-value: 0.002ANCOVA
Secondary
Change From Baseline in Quick Inventory of Depressive Symptoms, 16 Question Self-report (QIDS-SR)
This is a 16-item self reported questionnaire that measures depressive symptoms. Improvement reported as change in depressive score. Score ranges from 0 to 42, with higher numbers indicating more severe symptom reporting. Change: score at observation minus score at baseline.
Time frame: Baseline, Week 8
Population: FAS; LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Desvenlafaxine Succinate | Change From Baseline in Quick Inventory of Depressive Symptoms, 16 Question Self-report (QIDS-SR) | Baseline | 15.1 Units on a scale | Standard Deviation 3.22 |
| Desvenlafaxine Succinate | Change From Baseline in Quick Inventory of Depressive Symptoms, 16 Question Self-report (QIDS-SR) | Change at Week 8 | -5.9 Units on a scale | Standard Deviation 4.93 |
| Placebo | Change From Baseline in Quick Inventory of Depressive Symptoms, 16 Question Self-report (QIDS-SR) | Baseline | 14.8 Units on a scale | Standard Deviation 3.6 |
| Placebo | Change From Baseline in Quick Inventory of Depressive Symptoms, 16 Question Self-report (QIDS-SR) | Change at Week 8 | -5.2 Units on a scale | Standard Deviation 4.48 |
p-value: 0.158ANCOVA
Secondary
Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Week 8
10 centimeter (cm) line (Visual Analog Scale) marked by participant. Intensity of pain range (over past week): 0 = no pain to 10 = worst possible pain. Change: score at observation minus score at baseline.
Time frame: Baseline, Week 8
Population: FAS; LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Desvenlafaxine Succinate | Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Week 8 | Baseline | 4.0 cm | Standard Deviation 2.9 |
| Desvenlafaxine Succinate | Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Week 8 | Change at Week 8 | -1.5 cm | Standard Deviation 2.69 |
| Placebo | Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Week 8 | Baseline | 4.0 cm | Standard Deviation 2.98 |
| Placebo | Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Week 8 | Change at Week 8 | -0.8 cm | Standard Deviation 2.72 |
p-value: <0.001ANCOVA
Secondary
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I)
CGI-I: 7-point scale in which the clinician rated how much the participant's condition has changed compared to baseline. Scores ranged 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. Higher score = more affected.
Time frame: Week 8
Population: FAS; LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Desvenlafaxine Succinate | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Minimally Improved | 53 participants |
| Desvenlafaxine Succinate | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Minimally Worse | 6 participants |
| Desvenlafaxine Succinate | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Much Improved | 67 participants |
| Desvenlafaxine Succinate | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Much Worse | 2 participants |
| Desvenlafaxine Succinate | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | No Change | 37 participants |
| Desvenlafaxine Succinate | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Very Much Worse | 0 participants |
| Desvenlafaxine Succinate | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Very Much Improved | 51 participants |
| Placebo | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Very Much Worse | 0 participants |
| Placebo | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Very Much Improved | 39 participants |
| Placebo | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Much Improved | 37 participants |
| Placebo | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Minimally Improved | 62 participants |
| Placebo | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | No Change | 69 participants |
| Placebo | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Minimally Worse | 6 participants |
| Placebo | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) | Much Worse | 3 participants |
p-value: <0.001Cochran-Mantel-Haenszel