Major Depressive Disorder
Conditions
Keywords
MDD
Brief summary
This study will be conducted with the aim of investigating the efficacy, safety and tolerability of 10 mg/day Vortioxetine in Asian patients compared to an approved active comparator (venlafaxine extended release 150 mg/day).
Interventions
10 mg/day
150 mg/day
Sponsors
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The patient suffers from recurrent MDD as the primary diagnosis according to DSM-IVTR™ criteria. The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI) * The patient has a MADRS total score ≥26 * The patient has a CGI-S score ≥4 * The reported duration of the current MDE is ≥3 months. Other inclusion criteria may apply.
Exclusion criteria
\- The patient meets any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MADRS Total Score at Week 8 | Baseline and Week 8 | Montgomery and Asberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60. The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MADRS Response at Week 8 (Response Defined as a ≥50% Decrease in the MADRS Total Score From Baseline) | Week 8 | — |
| Remission at Week 8 (Remission Defined as a MADRS Total Score ≤10) | Week 8 | — |
| Change in CGI-S Score From Baseline to Week 8 | Baseline and Week 8 | Clinical Global Impression Scale - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher score indicates that the subject is more ill, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. |
| Change in HAM-A Total Score From Baseline to Week 8 | Baseline and Week 8 | Hamilton Anxiety Rating Scale (HAM-A) is a 14-item rating scale designed to assess the global anxiety. Each symptom is rated from 0 (absent) to 4 (maximum severity). The total score of the 14 items ranges from 0 to 56. Higher score indicates greater anxiety, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. |
| Number of Adverse Events | Baseline to Week 12 | — |
| CGI-I Score at Week 8 | Week 8 | The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. Higher score = more affected. |
Participant flow
Recruitment details
In- or outpatients with a primary diagnosis of recurrent of Major Depressive Disorder (MDD) were recruited for this study from China, South Korea, Taiwan, and Thailand.
Pre-assignment details
A Screening Visit was held approximately 7 days prior to group assignment (group assignment was held during the Baseline Visit). Patients who met each of the inclusion criteria at the Screening and Baseline Visits and none of the exclusion criteria at the Screening and/or Baseline Visit were eligible to participate in this study.
Participants by arm
| Arm | Count |
|---|---|
| Vortioxetine Vortioxetine (Lu AA21004): 10 mg/day | 211 |
| Venlafaxine Venlafaxine extended release: 150 mg/day | 226 |
| Total | 437 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative or other reason(s) | 4 | 3 |
| Overall Study | Adverse Event | 14 | 32 |
| Overall Study | Lack of Efficacy | 8 | 3 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Non-compliance | 2 | 4 |
| Overall Study | Protocol Violation | 1 | 5 |
| Overall Study | Withdrawal of consent | 5 | 13 |
Baseline characteristics
| Characteristic | Vortioxetine | Venlafaxine | Total |
|---|---|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 12.4 | 40.7 years STANDARD_DEVIATION 12.3 | 40.1 years STANDARD_DEVIATION 12.3 |
| CGI-S score | 4.8 units on a scale STANDARD_DEVIATION 0.7 | 4.9 units on a scale STANDARD_DEVIATION 0.7 | 4.9 units on a scale STANDARD_DEVIATION 0.7 |
| HAM-A total score | 20.6 units on a scale STANDARD_DEVIATION 7.3 | 21.1 units on a scale STANDARD_DEVIATION 7 | 20.9 units on a scale STANDARD_DEVIATION 7.1 |
| MADRS total score | 32.3 units on a scale STANDARD_DEVIATION 4.6 | 32.3 units on a scale STANDARD_DEVIATION 4.5 | 32.3 units on a scale STANDARD_DEVIATION 4.6 |
| Sex: Female, Male Female | 123 Participants | 139 Participants | 262 Participants |
| Sex: Female, Male Male | 88 Participants | 87 Participants | 175 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 90 / 211 | 124 / 226 |
| serious Total, serious adverse events | 2 / 211 | 8 / 226 |
Outcome results
Primary
Change From Baseline in MADRS Total Score at Week 8
Montgomery and Asberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60. The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Time frame: Baseline and Week 8
Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine | Change From Baseline in MADRS Total Score at Week 8 | -19.36 units on a scale | Standard Error 0.7 |
| Venlafaxine | Change From Baseline in MADRS Total Score at Week 8 | -18.16 units on a scale | Standard Error 0.68 |
Comparison: The sample size calculation was based on a non-inferiority comparison of the treatment groups in the change from baseline to Week 8 in MADRS total score using a two-sided 95% CI against a margin of +2.5 points. Assuming a standard deviation of 9.0 points and an expected true mean difference between treatments of 0 points, a total of 410 patients (205 per treatment group) were needed to provide a power of 80% for correctly concluding non-inferiority.p-value: 0.19995% CI: [-3.03, 0.63]ANCOVA
Secondary
CGI-I Score at Week 8
The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. Higher score = more affected.
Time frame: Week 8
Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine | CGI-I Score at Week 8 | 1.99 units on a scale | Standard Error 0.08 |
| Venlafaxine | CGI-I Score at Week 8 | 2.14 units on a scale | Standard Error 0.08 |
Comparison: The same ANCOVA methodology as for the primary endpoint was used.p-value: 0.17495% CI: [-0.35, 0.06]ANCOVA
Secondary
Change in CGI-S Score From Baseline to Week 8
Clinical Global Impression Scale - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher score indicates that the subject is more ill, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Time frame: Baseline and Week 8
Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine | Change in CGI-S Score From Baseline to Week 8 | -2.26 units on a scale | Standard Error 0.09 |
| Venlafaxine | Change in CGI-S Score From Baseline to Week 8 | -2.12 units on a scale | Standard Error 0.09 |
Comparison: The same ANCOVA methodology as for the primary endpoint was used.p-value: 0.22895% CI: [-0.39, 0.09]ANCOVA
Secondary
Change in HAM-A Total Score From Baseline to Week 8
Hamilton Anxiety Rating Scale (HAM-A) is a 14-item rating scale designed to assess the global anxiety. Each symptom is rated from 0 (absent) to 4 (maximum severity). The total score of the 14 items ranges from 0 to 56. Higher score indicates greater anxiety, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Time frame: Baseline and Week 8
Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine | Change in HAM-A Total Score From Baseline to Week 8 | -11.38 units on a scale | Standard Error 0.48 |
| Venlafaxine | Change in HAM-A Total Score From Baseline to Week 8 | -10.56 units on a scale | Standard Error 0.47 |
Comparison: The same ANCOVA methodology as for the primary endpoint was used.p-value: 0.20795% CI: [-2.09, 0.45]ANCOVA
Secondary
MADRS Response at Week 8 (Response Defined as a ≥50% Decrease in the MADRS Total Score From Baseline)
Time frame: Week 8
Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vortioxetine | MADRS Response at Week 8 (Response Defined as a ≥50% Decrease in the MADRS Total Score From Baseline) | 66.5 percentage of patients |
| Venlafaxine | MADRS Response at Week 8 (Response Defined as a ≥50% Decrease in the MADRS Total Score From Baseline) | 61.4 percentage of patients |
p-value: 0.27295% CI: [0.84, 1.86]Regression, Logistic
Secondary
Number of Adverse Events
Time frame: Baseline to Week 12
Secondary
Remission at Week 8 (Remission Defined as a MADRS Total Score ≤10)
Time frame: Week 8
Population: The full-analysis set (FAS) comprises all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vortioxetine | Remission at Week 8 (Remission Defined as a MADRS Total Score ≤10) | 43.1 percentage of patients |
| Venlafaxine | Remission at Week 8 (Remission Defined as a MADRS Total Score ≤10) | 41.4 percentage of patients |
p-value: 0.73195% CI: [0.73, 1.58]Regression, Logistic