Depressive Disorder, Major
Conditions
Keywords
MDD, Major Depressive Disorder, Depression
Brief summary
The primary purpose of this study is to evaluate the efficacy and safety of two doses of DVS SR (50 and 100 mg/day) in the treatment of adults with Major Depressive Disorder.
Interventions
50 mg tablet, once daily dosing for 8 weeks
DRUGPlacebo
Matching placebo tablets and capsules, once daily dosing for 8 weeks
DRUGDuloxetine 60 mg/day
60 mg capsule, once daily dosing for 8 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Inclusion criteria
* A primary diagnosis of Major Depressive Disorder, single or recurrent episode, without psychotic features. * Depressive symptoms for at least 30 days before the screening visit. * Outpatient men and women at least 18 years of age.
Exclusion criteria
* Significant risk of suicide based on clinical judgment, including common suicidal thoughts and suicide having been considered as a possible solution even without specific plans or intent. * Any unstable hepatic, renal, pulmonary, cardiovascular (including uncontrolled hypertension), ophthalmologic, neurologic, or any other medical condition that might confound the study or put the subject at greater risk during study participation. * Current (within 12 months before baseline) psychoactive substance abuse or dependence (including alcohol), manic episode, posttraumatic stress disorder, obsessive-compulsive disorder, or a lifetime diagnosis of bipolar or psychotic disorder; b) current (within 12 months before baseline) generalized anxiety disorder, panic disorder, or social anxiety disorder; c) presence (within 12 months before baseline) of a clinically important personality disorder as assessed during the psychiatric assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HAM-D17 Total Score at Week 8 or Final On-therapy (FOT) Evaluation | Baseline and Week 8 or FOT | HAM-D17: a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0 = none/absent and 4 = most severe, for a maximum total score of 50. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean CGI-S Score at Week 8 or FOT Evaluation | Baseline and Week 8 or FOT | 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 participants). Higher score = more affected. |
| Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Baseline and Week 8 or FOT | MADRS 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 From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Baseline and Week 8 or FOT | Lassitude item of MADRS represents a difficulty in getting started or slowness in initiating and performing everyday activities. It is rated on a scale of 0-6: 0 = hardly any difficulty in getting started/no sluggishness; 2 = difficulties in starting activities; 4 = difficulties in starting simple routine activities which are carried out with effort; 6 = complete lassitude/unable to do anything without help. |
| Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | Week 8 or FOT | 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 relative to the baseline assessment. Higher score = more affected. |
| Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Baseline and Week 8 or FOT | HAM-D energy subscale is a subset of the HAM-D17 that assesses 4 items associated with major depression. The scale uses HAM- D17 items 1, 7, 8 and 14. Item 14 is scored 0 to 2 (0=none/absent to 2=most severe) and all others are scored 0 to 4 (0=none/absent to 4=most severe). |
| Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Baseline and Week 8 or FOT | COVI anxiety scale measures the severity of anxiety symptoms on 3 items: verbal report, behavior and somatic complaints. Each dimension is assessed using a 5-point scale: 1 = not at all, 2 = somewhat, 3 = moderately, 4 = considerably, to 5 = Very much. Worst value is 15 and best value is 3. |
| Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Baseline and Week 8 or FOT | VAS-PI scale assesses intensity of back pain, chest pain, arms, legs or joint pain as well as overall pain intensity where 100 mm line (VAS) is marked by participant and intensity of pain ranges from 0 millimetre (mm) = no pain to 100 mm = worst possible pain. There were separate 0 to 100 mm VAS lines for each subcomponent of VAS-PI. |
| Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Baseline and Week 8 or FOT | HAM-D6: a standardized, clinician-administered rating scale that assesses 6 items characteristically associated with major depression and is a subset of HAM-D17. HAM-D6 score ranges from 0-22. The scale uses HAM-D17 items: 1, 2, 7, 8, 10 and 13. Item 13 is scored 0-2 (0=none and 2=severe) and all others are scored 0-4 (0=none/absent and 4=most severe). |
Countries
United States
Participant flow
Recruitment details
Study was conducted from 27 September 2006 to 28 September 2007 in United States (US) only.
Pre-assignment details
A total of 925 participants were screened for this study and 638 participants were randomized. The remaining 287 participants were not randomized due to screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to desvenlafaxine succinate monohydrate sustained release (DVS SR) 50 milligram (mg) and 100 mg tablet and duloxetine 60 mg capsule daily until Day 56 (Week 8) or early termination (ET); then placebo matched to DVS SR 50 mg and 100 mg tablet and duloxetine 30 mg capsule for days 57-63 (Taper week). | 161 |
| DVS SR 50 mg DVS SR 50 mg tablet and placebo matched to DVS SR 100 mg tablet and duloxetine 60 mg capsule daily until Day 56 (Week 8) or ET; then placebo matched to DVS SR 50 mg and 100 mg tablet and duloxetine 30 mg capsule for days 57-63 (Taper week). | 148 |
| DVS SR 100 mg DVS SR 50 mg tablet and placebo matched to DVS SR 100 mg tablet and duloxetine 60 mg capsule daily for days 1-7; then DVS titrated up to 100 mg tablet, placebo matched to DVS SR 50 mg and duloxetine 60 mg capsule daily from days 8-56 (Week 8) or ET; then tapered to DVS SR 50 mg tablet and placebo matched to DVS SR 100 mg tablet and duloxetine 30 mg capsule for days 57-63 (Taper week). | 150 |
| Duloxetine 60 mg Duloxetine 60 mg capsule and placebo matched to DVS SR 50 mg and DVS SR 100 mg tablet daily until Day 56 (Week 8) or ET; then duloxetine 30 mg capsule and placebo matched to DVS SR 50 mg and 100 mg tablet for days 57-63 (Taper week). | 157 |
| Total | 616 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 8 | 11 | 20 |
| Overall Study | Failed to return | 1 | 3 | 2 | 2 |
| Overall Study | Lack of Efficacy | 7 | 3 | 3 | 1 |
| Overall Study | Lost to Follow-up | 6 | 12 | 7 | 7 |
| Overall Study | Other | 2 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 5 | 0 | 5 | 6 |
| Overall Study | Randomized but not treated | 3 | 7 | 10 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 2 | 5 | 2 |
Baseline characteristics
| Characteristic | Placebo | DVS SR 50 mg | DVS SR 100 mg | Duloxetine 60 mg | Total |
|---|---|---|---|---|---|
| Age Continuous | 39.24 Years STANDARD_DEVIATION 12.74 | 40.67 Years STANDARD_DEVIATION 13.2 | 38.77 Years STANDARD_DEVIATION 12.07 | 38.94 Years STANDARD_DEVIATION 12.01 | 39.39 Years STANDARD_DEVIATION 12.5 |
| Clinical global impressions scale-severity (CGI-S) score | 4.39 Units on a Scale STANDARD_DEVIATION 0.54 | 4.29 Units on a Scale STANDARD_DEVIATION 0.48 | 4.31 Units on a Scale STANDARD_DEVIATION 0.49 | 4.28 Units on a Scale STANDARD_DEVIATION 0.46 | 4.32 Units on a Scale STANDARD_DEVIATION 0.5 |
| Hamilton psychiatric scale for depression-17 item (HAM-D17) total score | 23.86 Units on a Scale STANDARD_DEVIATION 2.68 | 23.49 Units on a Scale STANDARD_DEVIATION 2.52 | 23.49 Units on a Scale STANDARD_DEVIATION 2.55 | 22.99 Units on a Scale STANDARD_DEVIATION 2.45 | 23.46 Units on a Scale STANDARD_DEVIATION 2.57 |
| Sex: Female, Male Female | 94 Participants | 102 Participants | 99 Participants | 104 Participants | 399 Participants |
| Sex: Female, Male Male | 67 Participants | 46 Participants | 51 Participants | 53 Participants | 217 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 129 / 161 | 134 / 148 | 134 / 150 | 141 / 157 |
| serious Total, serious adverse events | 2 / 161 | 2 / 148 | 2 / 150 | 1 / 157 |
Outcome results
Primary
Change From Baseline in HAM-D17 Total Score at Week 8 or Final On-therapy (FOT) Evaluation
HAM-D17: a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0 = none/absent and 4 = most severe, for a maximum total score of 50.
Time frame: Baseline and Week 8 or FOT
Population: Intent-to-treat (ITT) population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HAM-D17 Total Score at Week 8 or Final On-therapy (FOT) Evaluation | -8.68 Units on a Scale | Standard Error 0.58 |
| DVS SR 50 mg | Change From Baseline in HAM-D17 Total Score at Week 8 or Final On-therapy (FOT) Evaluation | -9.75 Units on a Scale | Standard Error 0.6 |
| DVS SR 100 mg | Change From Baseline in HAM-D17 Total Score at Week 8 or Final On-therapy (FOT) Evaluation | -10.5 Units on a Scale | Standard Error 0.6 |
| Duloxetine 60 mg | Change From Baseline in HAM-D17 Total Score at Week 8 or Final On-therapy (FOT) Evaluation | -10.3 Units on a Scale | Standard Error 0.6 |
Comparison: For DVS SR 50 mg, HAM-D17 total score was evaluated using analysis of covariance (ANCOVA) with treatment and site as factors and baseline HAM-D17 score as the covariate.p-value: 0.19895% CI: [-0.6, 2.7]ANCOVA
Comparison: For DVS SR 100 mg, HAM-D17 total score was evaluated using ANCOVA with treatment and site as factors and baseline HAM-D17 score as the covariate.p-value: 0.02895% CI: [0.2, 3.4]ANCOVA
Comparison: For Duloxetine 60 mg, HAM-D17 total score was evaluated using ANCOVA with treatment and site as factors and baseline HAM-D17 score as the covariate.p-value: 0.04795% CI: [0, 3.4]ANCOVA
Secondary
Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation
COVI anxiety scale measures the severity of anxiety symptoms on 3 items: verbal report, behavior and somatic complaints. Each dimension is assessed using a 5-point scale: 1 = not at all, 2 = somewhat, 3 = moderately, 4 = considerably, to 5 = Very much. Worst value is 15 and best value is 3.
Time frame: Baseline and Week 8 or FOT
Population: ITT population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Baseline | 6.50 Units on a Scale | — |
| Placebo | Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -1.02 Units on a Scale | Standard Error 0.12 |
| DVS SR 50 mg | Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -1.15 Units on a Scale | Standard Error 0.13 |
| DVS SR 50 mg | Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Baseline | 6.30 Units on a Scale | — |
| DVS SR 100 mg | Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Baseline | 6.30 Units on a Scale | — |
| DVS SR 100 mg | Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -1.35 Units on a Scale | Standard Error 0.13 |
| Duloxetine 60 mg | Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Baseline | 6.30 Units on a Scale | — |
| Duloxetine 60 mg | Change From Baseline in Covi Anxiety Scale at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -1.47 Units on a Scale | Standard Error 0.13 |
Comparison: For DVS SR 50 mg, Covi anxiety scale was evaluated using ANCOVA with treatment and site as factors and baseline Covi anxiety score as the covariate.p-value: 0.44595% CI: [-0.2, 0.5]ANCOVA
Comparison: For DVS SR 100 mg, Covi anxiety scale was evaluated using ANCOVA with treatment and site as factors and baseline Covi anxiety score as the covariate.p-value: 0.05695% CI: [0, 0.7]ANCOVA
Comparison: For Duloxetine 60 mg, Covi anxiety scale was evaluated using ANCOVA with treatment and site as factors and baseline Covi anxiety score as the covariate.p-value: 0.00695% CI: [0.1, 0.9]ANCOVA
Secondary
Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation
HAM-D6: a standardized, clinician-administered rating scale that assesses 6 items characteristically associated with major depression and is a subset of HAM-D17. HAM-D6 score ranges from 0-22. The scale uses HAM-D17 items: 1, 2, 7, 8, 10 and 13. Item 13 is scored 0-2 (0=none and 2=severe) and all others are scored 0-4 (0=none/absent and 4=most severe).
Time frame: Baseline and Week 8 or FOT
Population: ITT population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Baseline | 13.00 Units on a Scale | — |
| Placebo | Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -4.82 Units on a Scale | Standard Error 0.33 |
| DVS SR 50 mg | Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Baseline | 12.80 Units on a Scale | — |
| DVS SR 50 mg | Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -5.41 Units on a Scale | Standard Error 0.35 |
| DVS SR 100 mg | Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -6.15 Units on a Scale | Standard Error 0.34 |
| DVS SR 100 mg | Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Baseline | 12.90 Units on a Scale | — |
| Duloxetine 60 mg | Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -5.91 Units on a Scale | Standard Error 0.36 |
| Duloxetine 60 mg | Change From Baseline in HAM-D6 Total Score at Week 8 or FOT Evaluation | Baseline | 12.90 Units on a Scale | — |
Comparison: For DVS SR 50 mg, HAM-D6 score was evaluated using ANCOVA with treatment and site as factors and baseline HAM-D6 score as the covariate.p-value: 0.21595% CI: [-0.3, 1.5]ANCOVA
Comparison: For DVS SR 100 mg, HAM-D6 score was evaluated using ANCOVA with treatment and site as factors and baseline HAM-D6 score as the covariate.p-value: 0.00595% CI: [0.4, 2.3]ANCOVA
Comparison: For Duloxetine 60 mg, HAM-D6 score was evaluated using ANCOVA with treatment and site as factors and baseline HAM-D6 score as the covariate.p-value: 0.02495% CI: [0.2, 2.1]ANCOVA
Secondary
Change From Baseline in Mean CGI-S Score at Week 8 or FOT Evaluation
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 participants). Higher score = more affected.
Time frame: Baseline and Week 8 or FOT
Population: ITT population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean CGI-S Score at Week 8 or FOT Evaluation | -1.10 Units on a Scale | Standard Error 0.09 |
| DVS SR 50 mg | Change From Baseline in Mean CGI-S Score at Week 8 or FOT Evaluation | -1.25 Units on a Scale | Standard Error 0.1 |
| DVS SR 100 mg | Change From Baseline in Mean CGI-S Score at Week 8 or FOT Evaluation | -1.44 Units on a Scale | Standard Error 0.1 |
| Duloxetine 60 mg | Change From Baseline in Mean CGI-S Score at Week 8 or FOT Evaluation | -1.41 Units on a Scale | Standard Error 0.1 |
Comparison: For DVS SR 50 mg, CGI-S was evaluated using ANCOVA with treatment and site as factors and baseline CGI-S score as the covariate.p-value: 0.24895% CI: [-0.1, 0.4]ANCOVA
Comparison: For DVS SR 100 mg, CGI-S was evaluated using ANCOVA with treatment and site as factors and baseline CGI-S score as the covariate.p-value: 0.01195% CI: [0.1, 0.6]ANCOVA
Comparison: For Duloxetine 60 mg, CGI-S was evaluated using ANCOVA with treatment and site as factors and baseline CGI-S score as the covariate.p-value: 0.02695% CI: [0, 0.6]ANCOVA
Secondary
Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation
MADRS 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: Baseline and Week 8 or FOT
Population: ITT population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Baseline | 31.10 Units on a Scale | — |
| Placebo | Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -11.00 Units on a Scale | Standard Error 0.82 |
| DVS SR 50 mg | Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -12.70 Units on a Scale | Standard Error 0.85 |
| DVS SR 50 mg | Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Baseline | 30.10 Units on a Scale | — |
| DVS SR 100 mg | Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -14.40 Units on a Scale | Standard Error 0.84 |
| DVS SR 100 mg | Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Baseline | 30.70 Units on a Scale | — |
| Duloxetine 60 mg | Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -14.40 Units on a Scale | Standard Error 0.87 |
| Duloxetine 60 mg | Change From Baseline in Montgomery and Asberg Depression Rating Scale (MADRS) Total Score at Week 8 or FOT Evaluation | Baseline | 30.80 Units on a Scale | — |
Comparison: For DVS SR 50 mg, MADRS total score was evaluated using ANCOVA with treatment and site as factors and baseline MADRS score as the covariate.p-value: 0.14995% CI: [-0.6, 4]ANCOVA
Comparison: For DVS SR 100 mg, MADRS total score was evaluated using ANCOVA with treatment and site as factors and baseline MADRS score as the covariate.p-value: 0.00495% CI: [1.1, 5.6]ANCOVA
Comparison: For Duloxetine 60 mg, MADRS total score was evaluated using ANCOVA with treatment and site as factors and baseline MADRS score as the covariate.p-value: 0.00595% CI: [1.1, 5.8]ANCOVA
Secondary
Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation
HAM-D energy subscale is a subset of the HAM-D17 that assesses 4 items associated with major depression. The scale uses HAM- D17 items 1, 7, 8 and 14. Item 14 is scored 0 to 2 (0=none/absent to 2=most severe) and all others are scored 0 to 4 (0=none/absent to 4=most severe).
Time frame: Baseline and Week 8 or FOT
Population: ITT population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Baseline | 8.38 Units on a Scale | — |
| Placebo | Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -3.13 Units on a Scale | Standard Error 0.23 |
| DVS SR 50 mg | Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -3.66 Units on a Scale | Standard Error 0.23 |
| DVS SR 50 mg | Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Baseline | 8.43 Units on a Scale | — |
| DVS SR 100 mg | Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Baseline | 8.51 Units on a Scale | — |
| DVS SR 100 mg | Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -3.92 Units on a Scale | Standard Error 0.23 |
| Duloxetine 60 mg | Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Baseline | 8.38 Units on a Scale | — |
| Duloxetine 60 mg | Change From Baseline in the HAM-D Energy Subscale Score at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -3.80 Units on a Scale | Standard Error 0.24 |
Comparison: For DVS SR 50 mg, HAM-D energy subscale score was evaluated using ANCOVA with treatment and site as factors and baseline HAM-D energy score as the covariate.p-value: 0.195% CI: [-0.1, 1.17]ANCOVA
Comparison: For DVS SR 100 mg, HAM-D energy subscale score was evaluated using ANCOVA with treatment and site as factors and baseline HAM-D energy score as the covariate.p-value: 0.01495% CI: [0.16, 1.42]ANCOVA
Comparison: For Duloxetine 60 mg, HAM-D energy subscale score was evaluated using ANCOVA with treatment and site as factors and baseline HAM-D energy score as the covariate.p-value: 0.03295% CI: [0.06, 1.38]ANCOVA
Secondary
Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation
Lassitude item of MADRS represents a difficulty in getting started or slowness in initiating and performing everyday activities. It is rated on a scale of 0-6: 0 = hardly any difficulty in getting started/no sluggishness; 2 = difficulties in starting activities; 4 = difficulties in starting simple routine activities which are carried out with effort; 6 = complete lassitude/unable to do anything without help.
Time frame: Baseline and Week 8 or FOT
Population: ITT population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Baseline | 3.49 Units on a Scale | — |
| Placebo | Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -1.27 Units on a Scale | Standard Error 0.12 |
| DVS SR 50 mg | Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -1.39 Units on a Scale | Standard Error 0.13 |
| DVS SR 50 mg | Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Baseline | 3.53 Units on a Scale | — |
| DVS SR 100 mg | Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Baseline | 3.70 Units on a Scale | — |
| DVS SR 100 mg | Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -1.54 Units on a Scale | Standard Error 0.13 |
| Duloxetine 60 mg | Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Baseline | 3.50 Units on a Scale | — |
| Duloxetine 60 mg | Change From Baseline in the Lassitude Item of the MADRS Scale at Week 8 or FOT Evaluation | Change at Week 8 or FOT | -1.26 Units on a Scale | Standard Error 0.12 |
Comparison: For DVS SR 50 mg, lassitude item of the MADRS score was evaluated using ANCOVA with treatment and site as factors and baseline lassitude item of the MADRS score as the covariate.p-value: 0.47395% CI: [-0.22, 0.46]ANCOVA
Comparison: For DVS SR 100 mg, lassitude item of the MADRS score was evaluated using ANCOVA with treatment and site as factors and baseline lassitude item of the MADRS score as the covariate.p-value: 0.11995% CI: [-0.07, 0.61]ANCOVA
Comparison: For Duloxetine 60 mg, lassitude item of the MADRS score was evaluated using ANCOVA with treatment and site as factors and baseline lassitude item of the MADRS score as the covariate.p-value: 0.7195% CI: [-0.27, 0.4]ANCOVA
Secondary
Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation
VAS-PI scale assesses intensity of back pain, chest pain, arms, legs or joint pain as well as overall pain intensity where 100 mm line (VAS) is marked by participant and intensity of pain ranges from 0 millimetre (mm) = no pain to 100 mm = worst possible pain. There were separate 0 to 100 mm VAS lines for each subcomponent of VAS-PI.
Time frame: Baseline and Week 8 or FOT
Population: ITT population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Overall pain (Baseline) | 26.30 mm | — |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Stomach pain (Baseline) | 16.70 mm | — |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Back pain (Baseline) | 25.90 mm | — |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Chest pain (Baseline) | 9.40 mm | — |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Arms, legs or joint pain (Baseline) | 25.80 mm | — |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Overall pain (Change at Week 8 or FOT) | -5.61 mm | Standard Error 1.57 |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Stomach pain (Change at Week 8 or FOT) | -1.86 mm | Standard Error 1.62 |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Back pain (Change at Week 8 or FOT) | -7.04 mm | Standard Error 1.67 |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Chest pain (Change at Week 8 or FOT) | -1.95 mm | Standard Error 1.12 |
| Placebo | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Arms, legs or joint pain (Change at Week 8 or FOT) | -6.99 mm | Standard Error 1.7 |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Back pain (Baseline) | 32.90 mm | — |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Chest pain (Change at Week 8 or FOT) | -3.34 mm | Standard Error 1.17 |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Chest pain (Baseline) | 10.90 mm | — |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Arms, legs or joint pain (Baseline) | 29.10 mm | — |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Overall pain (Change at Week 8 or FOT) | -9.08 mm | Standard Error 1.64 |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Stomach pain (Change at Week 8 or FOT) | -4.98 mm | Standard Error 1.69 |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Arms, legs or joint pain (Change at Week 8 or FOT) | -8.98 mm | Standard Error 1.76 |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Back pain (Change at Week 8 or FOT) | -10.70 mm | Standard Error 1.74 |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Overall pain (Baseline) | 30.80 mm | — |
| DVS SR 50 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Stomach pain (Baseline) | 19.40 mm | — |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Back pain (Change at Week 8 or FOT) | -12.80 mm | Standard Error 1.73 |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Stomach pain (Change at Week 8 or FOT) | -6.42 mm | Standard Error 1.68 |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Arms, legs or joint pain (Change at Week 8 or FOT) | -11.90 mm | Standard Error 1.76 |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Overall pain (Baseline) | 25.90 mm | — |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Chest pain (Baseline) | 10.40 mm | — |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Overall pain (Change at Week 8 or FOT) | -10.30 mm | Standard Error 1.63 |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Chest pain (Change at Week 8 or FOT) | -3.90 mm | Standard Error 1.16 |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Stomach pain (Baseline) | 17.00 mm | — |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Arms, legs or joint pain (Baseline) | 28.70 mm | — |
| DVS SR 100 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Back pain (Baseline) | 28.30 mm | — |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Arms, legs or joint pain (Baseline) | 22.40 mm | — |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Back pain (Change at Week 8 or FOT) | -9.33 mm | Standard Error 1.83 |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Overall pain (Change at Week 8 or FOT) | -8.84 mm | Standard Error 1.74 |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Arms, legs or joint pain (Change at Week 8 or FOT) | -8.35 mm | Standard Error 1.64 |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Stomach pain (Change at Week 8 or FOT) | -4.38 mm | Standard Error 1.58 |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Stomach pain (Baseline) | 14.00 mm | — |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Back pain (Baseline) | 25.50 mm | — |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Chest pain (Baseline) | 6.60 mm | — |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Overall pain (Baseline) | 26.10 mm | — |
| Duloxetine 60 mg | Change From Baseline in Visual Analog Scale-Pain Intensity (VAS-PI) Overall and Subcomponent Score at Week 8 or FOT Evaluation | Chest pain (Change at Week 8 or FOT) | -1.67 mm | Standard Error 1.21 |
Comparison: For DVS SR 50 mg, overall VAS-PI score was evaluated using ANCOVA with treatment and site as factors and baseline VAS-PI score as the covariate.p-value: 0.12495% CI: [-0.9, 7.9]ANCOVA
Comparison: For DVS SR 100 mg, overall VAS-PI score was evaluated using ANCOVA with treatment and site as factors and baseline VAS-PI score as the covariate.p-value: 0.03595% CI: [0.3, 9.1]ANCOVA
Comparison: For Duloxetine 60 mg, overall VAS-PI score was evaluated using ANCOVA with treatment and site as factors and baseline VAS-PI score as the covariate.p-value: 0.09395% CI: [-0.7, 8.8]ANCOVA
Comparison: For DVS SR 50 mg, stomach pain score was evaluated using ANCOVA with treatment and site as factors and baseline stomach pain score as the covariate.p-value: 0.17795% CI: [-1.4, 7.7]ANCOVA
Comparison: For DVS SR 100 mg, stomach pain score was evaluated using ANCOVA with treatment and site as factors and baseline stomach pain score as the covariate.p-value: 0.04895% CI: [0.1, 9.1]ANCOVA
Comparison: For Duloxetine 60 mg, stomach pain score was evaluated using ANCOVA with treatment and site as factors and baseline stomach pain score as the covariate.p-value: 0.08895% CI: [-0.5, 8.1]ANCOVA
Comparison: For DVS SR 50 mg, back pain score was evaluated using ANCOVA with treatment and site as factors and baseline back pain score as the covariate.p-value: 0.12295% CI: [-1, 8.4]ANCOVA
Comparison: For DVS SR 100 mg, back pain score was evaluated using ANCOVA with treatment and site as factors and baseline back pain score as the covariate.p-value: 0.01595% CI: [1.1, 10.5]ANCOVA
Comparison: For Duloxetine 60 mg, back pain score was evaluated using ANCOVA with treatment and site as factors and baseline back pain score as the covariate.p-value: 0.10395% CI: [-0.8, 9.2]ANCOVA
Comparison: For DVS SR 50 mg, chest pain score was evaluated using ANCOVA with treatment and site as factors and baseline chest pain score as the covariate.p-value: 0.38495% CI: [-1.7, 4.5]ANCOVA
Comparison: For DVS SR 100 mg, chest pain score was evaluated using ANCOVA with treatment and site as factors and baseline chest pain score as the covariate.p-value: 0.22195% CI: [-1.2, 5.1]ANCOVA
Comparison: For Duloxetine 60 mg, chest pain score was evaluated using ANCOVA with treatment and site as factors and baseline chest pain score as the covariate.p-value: 0.41195% CI: [-1.9, 4.7]ANCOVA
Comparison: For DVS SR 50 mg, arms, legs, joint pain score was evaluated using ANCOVA with treatment and site as factors and baseline arms, legs, pain score as the covariate.p-value: 0.41295% CI: [-2.8, 6.7]ANCOVA
Comparison: For DVS SR 100 mg, arms, legs, joint pain score was evaluated using ANCOVA with treatment and site as factors and baseline arms, legs, pain score as the covariate.p-value: 0.04295% CI: [0.2, 9.6]ANCOVA
Comparison: For Duloxetine 60 mg, arms, legs, joint pain score was evaluated using ANCOVA with treatment and site as factors and baseline arms, legs, pain score as the covariate.p-value: 0.15595% CI: [-1.2, 7.8]ANCOVA
Secondary
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation
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 relative to the baseline assessment. Higher score = more affected.
Time frame: Week 8 or FOT
Population: ITT population included all randomized participants who had a baseline primary efficacy evaluation, had taken at least 1 dose of double-blind study medication, and had at least 1 primary efficacy evaluation after the first dose of double-blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 4 = No change | 57 Participants |
| Placebo | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 2 = Much improved | 32 Participants |
| Placebo | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 5 = Minimally worse | 5 Participants |
| Placebo | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 3 = Minimally improved | 35 Participants |
| Placebo | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 1 = Very much improved | 31 Participants |
| DVS SR 50 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 3 = Minimally improved | 47 Participants |
| DVS SR 50 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 4 = No change | 34 Participants |
| DVS SR 50 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 5 = Minimally worse | 2 Participants |
| DVS SR 50 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 2 = Much improved | 38 Participants |
| DVS SR 50 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 1 = Very much improved | 27 Participants |
| DVS SR 100 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 3 = Minimally improved | 28 Participants |
| DVS SR 100 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 1 = Very much improved | 45 Participants |
| DVS SR 100 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 2 = Much improved | 37 Participants |
| DVS SR 100 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 4 = No change | 37 Participants |
| DVS SR 100 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 5 = Minimally worse | 2 Participants |
| Duloxetine 60 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 4 = No change | 37 Participants |
| Duloxetine 60 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 2 = Much improved | 35 Participants |
| Duloxetine 60 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 1 = Very much improved | 45 Participants |
| Duloxetine 60 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 3 = Minimally improved | 37 Participants |
| Duloxetine 60 mg | Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) Score at Week 8 or FOT Evaluation | 5 = Minimally worse | 3 Participants |
Comparison: For DVS SR 50 mg, CGI-I was evaluated using Cochran-Mantel-Haenszel (CMH) test with treatment as a factor and controlling for center.p-value: 0.11Cochran-Mantel-Haenszel
Comparison: For DVS SR 100 mg, CGI-I was evaluated using CMH test with treatment as a factor and controlling for center.p-value: 0.009Cochran-Mantel-Haenszel
Comparison: For Duloxetine 60 mg, CGI-I was evaluated using CMH test with treatment as a factor and controlling for center.p-value: 0.008Cochran-Mantel-Haenszel