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Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02371980
Recruitment Status : Completed
First Posted : February 26, 2015
Results First Posted : April 17, 2020
Last Update Posted : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Vortioxetine
Drug: Placebo
Enrollment 1106
Recruitment Details Participants took part in the study at 74 investigative sites in the United States from 10 February 2015 to 25 April 2019.
Pre-assignment Details Participants with diagnosis of major depressive disorder (MDD) were enrolled to receive vortioxetine 10 mg in the Open-label Period for up to 16 weeks. Responders (defined below) were randomized in 1:1:1:1 ratio to receive vortioxetine 5 mg, 10 mg or 20 mg or placebo for up to 32 weeks in the Double-blind Period.
Arm/Group Title Open-label: Vortioxetine 10 mg Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Hide Arm/Group Description Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period. Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Period Title: Open-label Period
Started 1106 0 0 0 0
Completed 580 0 0 0 0
Not Completed 526 0 0 0 0
Reason Not Completed
Pretreatment Event/Adverse Event             63             0             0             0             0
Significant Protocol Deviation             19             0             0             0             0
Noncompliance with Study Drug             10             0             0             0             0
Lost to Follow-up             55             0             0             0             0
Voluntary Withdrawal             91             0             0             0             0
Pregnancy             1             0             0             0             0
Lack of Efficacy             116             0             0             0             0
Did not Meet Randomization Criteria             162             0             0             0             0
Reason not Specified             9             0             0             0             0
Period Title: Double-blind Period
Started 0 151 140 145 144
Completed 0 70 84 96 86
Not Completed 0 81 56 49 58
Reason Not Completed
Pretreatment Event/Adverse Event             0             4             3             2             9
Significant Protocol Deviation             0             2             7             3             3
Noncompliance with Study Drug             0             1             2             2             3
Lost to Follow-up             0             8             8             6             5
Voluntary Withdrawal             0             12             8             9             11
Relapse             0             50             25             25             26
Reason not Specified             0             3             3             2             1
Missing             0             1             0             0             0
Arm/Group Title Open-label: Vortioxetine 10 mg
Hide Arm/Group Description Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period.
Overall Number of Baseline Participants 1106
Hide Baseline Analysis Population Description
Safety Set for Open-label Period included all participant who received at least 1 dose of Open-label study medication. Baseline I is defined as the last non-missing observation prior to the first dose of open-label study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1106 participants
44.3  (13.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1106 participants
Female
807
  73.0%
Male
299
  27.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1106 participants
Hispanic or Latino
145
  13.1%
Not Hispanic or Latino
961
  86.9%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1106 participants
American Indian or Alaska Native
7
   0.6%
Asian
19
   1.7%
Native Hawaiian or Other Pacific Islander
10
   0.9%
Black or African American
258
  23.3%
White
790
  71.4%
More than one race
19
   1.7%
Unknown or Not Reported
3
   0.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 1106 participants
1106
 100.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 1106 participants
167.7  (9.38)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 1106 participants
82.92  (18.695)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 1106 participants
29.39  (5.731)
[1]
Measure Description: BMI=Weight (kg)/height (m^2)
Smoking Classification  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1106 participants
Participant has Never Smoked
705
  63.7%
Participant is a Current Smoker
215
  19.4%
Participant is an Ex-smoker
186
  16.8%
Alcohol Consumption  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1106 participants
Participant has Never Consumed
332
  30.0%
Consumes Once Monthly or Less Consumes Often
286
  25.9%
Consumes Once a Week
167
  15.1%
Consumes 2 to 6 Times per Week
159
  14.4%
Consumes Daily
11
   1.0%
Participant was an Ex-Drinker
151
  13.7%
1.Primary Outcome
Title Time From Randomization to Relapse of Major Depressive Disorder During the First 28 Weeks of the 32-Week Double-Blind Treatment Period
Hide Description Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored at date of withdrawal or date of Week 28 visit, whichever was earliest. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The inter-quartile range (IQR) was 25th percentile to 75th percentile.
Time Frame From date of double-blind randomization (Week 16) up to relapse or first 28 weeks of Double-blind Period which occurs first (Up to Week 44)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug.
Arm/Group Title Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Hide Arm/Group Description:
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Overall Number of Participants Analyzed 151 140 145 144
Median (Inter-Quartile Range)
Unit of Measure: weeks
NA [1] 
(12 to NA)
NA [1] 
(28 to NA)
NA [1] 
(28 to NA)
NA [1] 
(28 to NA)
[1]
Median and upper limit of IQR were not reached due to low number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind: Vortioxetine 5 mg
Comments Double-blind Vortioxetine 5mg Vs Double-blind Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments Gate-keeping fixed-sequence testing procedure was used for multiple comparisons.
Method Cox Proportional Hazards Model
Comments Cox proportional hazards model with a factor for treatment and baseline II MADRS total score as a covariate, using the exact method to handle ties.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.517
Confidence Interval (2-Sided) 95%
0.323 to 0.828
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-blind: Vortioxetine 10 mg
Comments Double-blind Vortioxetine 10 mg Vs Double-blind Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Gate-keeping fixed-sequence testing procedure was used for multiple comparisons.
Method Cox Proportional Hazards Model
Comments Cox proportional hazards model with a factor for treatment and baseline II MADRS total score as a covariate, using the exact method to handle ties.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.476
Confidence Interval (2-Sided) 95%
0.296 to 0.767
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-blind: Vortioxetine 20 mg
Comments Double-blind Vortioxetine 20 mg Vs Double-blind Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Gate-keeping fixed-sequence testing procedure was used for multiple comparisons.
Method Cox Proportional Hazards Model
Comments Cox proportional hazards model with a factor for treatment and baseline II MADRS total score as a covariate, using the exact method to handle ties.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.483
Confidence Interval (2-Sided) 95%
0.298 to 0.782
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Hide Description MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher score indicates greater severity of symptoms. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. Mixed model for repeated measures (MMRM) was used for analyses.
Time Frame Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Hide Arm/Group Description:
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Overall Number of Participants Analyzed 151 140 145 144
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
Change From BL II at Week 2 Number Analyzed 148 participants 138 participants 144 participants 140 participants
2.70  (0.461) 2.23  (0.490) 1.47  (0.471) 2.29  (0.481)
Change From BL II at Week 4 Number Analyzed 136 participants 132 participants 137 participants 125 participants
4.99  (0.576) 2.56  (0.599) 1.98  (0.581) 2.48  (0.602)
Change From BL II at Week 8 Number Analyzed 121 participants 123 participants 128 participants 116 participants
5.98  (0.688) 3.03  (0.698) 2.14  (0.679) 2.97  (0.708)
Change From BL II at Week 12 Number Analyzed 104 participants 114 participants 117 participants 110 participants
6.43  (0.704) 3.51  (0.701) 1.92  (0.684) 2.79  (0.707)
Change From BL II at Week 16 Number Analyzed 90 participants 108 participants 113 participants 105 participants
5.77  (0.724) 3.73  (0.707) 2.08  (0.688) 3.14  (0.712)
Change From BL II at Week 20 Number Analyzed 83 participants 102 participants 107 participants 100 participants
5.95  (0.699) 3.34  (0.673) 1.86  (0.653) 3.18  (0.675)
Change From BL II at Week 24 Number Analyzed 78 participants 95 participants 103 participants 97 participants
5.69  (0.765) 3.78  (0.733) 2.19  (0.707) 3.16  (0.730)
Change From BL II at Week 28 Number Analyzed 71 participants 90 participants 100 participants 91 participants
5.07  (0.774) 3.18  (0.730) 2.72  (0.699) 3.20  (0.726)
Change From BL II at Week 32 Number Analyzed 67 participants 85 participants 94 participants 87 participants
6.55  (0.858) 3.46  (0.815) 2.58  (0.784) 2.97  (0.815)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.421
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean (LSM) Difference
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-1.63 to 0.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.590
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.23
Confidence Interval (2-Sided) 95%
-2.39 to -0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.589
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.488
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-1.57 to 0.75
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.592
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.43
Confidence Interval (2-Sided) 95%
-3.93 to -0.93
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.765
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.00
Confidence Interval (2-Sided) 95%
-4.49 to -1.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.761
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.50
Confidence Interval (2-Sided) 95%
-4.02 to -0.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.775
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.95
Confidence Interval (2-Sided) 95%
-4.76 to -1.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.924
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.84
Confidence Interval (2-Sided) 95%
-5.64 to -2.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.919
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.00
Confidence Interval (2-Sided) 95%
-4.84 to -1.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.939
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.92
Confidence Interval (2-Sided) 95%
-4.76 to -1.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.938
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -4.51
Confidence Interval (2-Sided) 95%
-6.34 to -2.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.934
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.64
Confidence Interval (2-Sided) 95%
-5.50 to -1.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.949
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.04
Confidence Interval (2-Sided) 95%
-3.92 to -0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.957
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.69
Confidence Interval (2-Sided) 95%
-5.55 to -1.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.952
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.63
Confidence Interval (2-Sided) 95%
-4.52 to -0.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.967
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.61
Confidence Interval (2-Sided) 95%
-4.40 to -0.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.912
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -4.09
Confidence Interval (2-Sided) 95%
-5.86 to -2.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.906
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.76
Confidence Interval (2-Sided) 95%
-4.57 to -0.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.921
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.92
Confidence Interval (2-Sided) 95%
-3.89 to 0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.008
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.50
Confidence Interval (2-Sided) 95%
-5.46 to -1.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.997
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.53
Confidence Interval (2-Sided) 95%
-4.51 to -0.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.011
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.061
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.90
Confidence Interval (2-Sided) 95%
-3.88 to 0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.012
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -2.36
Confidence Interval (2-Sided) 95%
-4.31 to -0.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.997
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.88
Confidence Interval (2-Sided) 95%
-3.87 to 0.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.015
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter MMRM Model
Estimated Value -3.09
Confidence Interval (2-Sided) 95%
-5.31 to -0.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.136
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.97
Confidence Interval (2-Sided) 95%
-6.16 to -1.77
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.122
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -3.58
Confidence Interval (2-Sided) 95%
-5.82 to -1.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.143
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed
Hide Description The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participant who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness on the following scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. MMRM was used for analyses.
Time Frame Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.
Arm/Group Title Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Hide Arm/Group Description:
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Overall Number of Participants Analyzed 151 140 145 144
Least Squares Mean (Standard Error)
Unit of Measure: scores on scale
Change From BL II at Week 2 Number Analyzed 147 participants 138 participants 144 participants 140 participants
0.35  (0.065) 0.32  (0.069) 0.26  (0.067) 0.27  (0.068)
Change From BL II at Week 4 Number Analyzed 135 participants 132 participants 135 participants 125 participants
0.61  (0.075) 0.32  (0.078) 0.30  (0.076) 0.25  (0.078)
Change From BL II at Week 8 Number Analyzed 121 participants 122 participants 127 participants 115 participants
0.68  (0.091) 0.38  (0.092) 0.29  (0.089) 0.30  (0.093)
Change From BL II at Week 12 Number Analyzed 104 participants 113 participants 116 participants 109 participants
0.74  (0.092) 0.46  (0.091) 0.24  (0.089) 0.35  (0.092)
Change From BL II at Week 16 Number Analyzed 90 participants 107 participants 113 participants 104 participants
0.62  (0.094) 0.50  (0.091) 0.25  (0.088) 0.34  (0.091)
Change From BL II at Week 20 Number Analyzed 83 participants 102 participants 107 participants 100 participants
0.61  (0.094) 0.40  (0.089) 0.17  (0.086) 0.28  (0.089)
Change From BL II at Week 24 Number Analyzed 77 participants 94 participants 103 participants 97 participants
0.60  (0.103) 0.45  (0.098) 0.24  (0.094) 0.37  (0.097)
Change From BL II at Week 28 Number Analyzed 70 participants 89 participants 100 participants 91 participants
0.45  (0.101) 0.33  (0.094) 0.30  (0.090) 0.34  (0.093)
Change From BL II at Week 32 Number Analyzed 66 participants 85 participants 94 participants 87 participants
0.59  (0.108) 0.41  (0.101) 0.26  (0.097) 0.22  (0.100)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.732
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.20 to 0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.085
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.273
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.26 to 0.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.085
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.361
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.24 to 0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.085
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.48 to -0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.099
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Least Squares Mean Difference
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.50 to -0.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.099
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.55 to -0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.100
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.54 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.121
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.63 to -0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.121
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.62 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.123
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method Least Squares Mean Difference
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.51 to -0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.122
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.74 to -0.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.122
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.63 to -0.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.124
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.333
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.36 to 0.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.123
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.61 to -0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.122
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.53 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.124
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.092
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.44 to 0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.121
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-0.67 to -0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.121
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 20
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.57 to -0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.122
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.248
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.42 to 0.11
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.135
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.63 to -0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.133
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.087
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.50 to 0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.135
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.362
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.38 to 0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.131
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.251
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.40 to 0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.129
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.391
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.37 to 0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.131
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Change From Baseline II at Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.209
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.45 to 0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.141
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Change From Baseline II at Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.60 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.139
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Change From Baseline II at Week 32
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method MMRM
Comments MMRM with treatment, visit, BL II score, treatment by visit interaction as fixed factors, center as random effect, and unstructured covariance matrix.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.65 to -0.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.141
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Global Impression Scale-Global Improvement Scale (CGI-I) Score
Hide Description The CGI-I scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Time Frame Week 32
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. Overall number of participants analyzed is the number of participants with data available for analyses.
Arm/Group Title Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Hide Arm/Group Description:
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Overall Number of Participants Analyzed 119 120 126 144
Mean (Standard Deviation)
Unit of Measure: scores on scale
4.4  (1.47) 3.9  (1.51) 3.5  (1.72) 3.7  (1.56)
5.Secondary Outcome
Title Time From Randomization to Relapse of Major Depressive Disorder During the Entire 32-Week Double-Blind Treatment Period
Hide Description Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The IQR was 25th percentile to 75th percentile.
Time Frame From date of double-blind randomization (Week 16) up to relapse or 32 weeks of Double-blind Period which occurs first (Up to Week 44)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug.
Arm/Group Title Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Hide Arm/Group Description:
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Overall Number of Participants Analyzed 151 140 145 144
Median (Inter-Quartile Range)
Unit of Measure: weeks
NA [1] 
(12 to NA)
NA [1] 
(32 to NA)
NA [1] 
(32 to NA)
NA [1] 
(32 to NA)
[1]
Median and upper limit of IQR was not reached due to low number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 5 mg
Comments Double-blind Vortioxetine 5mg Vs Double-blind Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Gate-keeping fixed-sequence testing procedure was used for multiple comparisons.
Method Cox Proportional Hazards Model
Comments Cox proportional hazards model with a factor for treatment and baseline II MADRS total score as a covariate, using the exact method to handle ties.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.481
Confidence Interval (2-Sided) 95%
0.302 to 0.766
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 10 mg
Comments Double-blind Vortioxetine 10 mg Vs Double-blind Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Gate-keeping fixed-sequence testing procedure was used for multiple comparisons.
Method Cox Proportional Hazards Model
Comments Cox proportional hazards model with a factor for treatment and baseline II MADRS total score as a covariate, using the exact method to handle ties.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.455
Confidence Interval (2-Sided) 95%
0.286 to 0.725
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Double-blind: Placebo, Double-blind: Vortioxetine 20 mg
Comments Double-blind Vortioxetine 20 mg Vs Double-blind Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Gate-keeping fixed-sequence testing procedure was used for multiple comparisons.
Method Cox Proportional Hazards Model
Comments Cox proportional hazards model with a factor for treatment and baseline II MADRS total score as a covariate, using the exact method to handle ties.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.484
Confidence Interval (2-Sided) 95%
0.304 to 0.771
Estimation Comments [Not Specified]
Time Frame From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Open-label: Vortioxetine 10 mg Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Hide Arm/Group Description Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period. Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period. Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
All-Cause Mortality
Open-label: Vortioxetine 10 mg Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/1106 (0.00%)   0/151 (0.00%)   0/140 (0.00%)   1/145 (0.69%)   0/144 (0.00%) 
Hide Serious Adverse Events
Open-label: Vortioxetine 10 mg Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/1106 (0.81%)   1/151 (0.66%)   3/140 (2.14%)   4/145 (2.76%)   0/144 (0.00%) 
Cardiac disorders           
Cardiac failure  1  0/1106 (0.00%)  1/151 (0.66%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Ear and labyrinth disorders           
Vertigo  1  0/1106 (0.00%)  0/151 (0.00%)  1/140 (0.71%)  0/145 (0.00%)  0/144 (0.00%) 
Gastrointestinal disorders           
Abdominal pain upper  1  1/1106 (0.09%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Hepatobiliary disorders           
Cholecystitis acute  1  1/1106 (0.09%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Infections and infestations           
Post procedural cellulitis  1  0/1106 (0.00%)  0/151 (0.00%)  0/140 (0.00%)  1/145 (0.69%)  0/144 (0.00%) 
Pyelonephritis  1  0/1106 (0.00%)  0/151 (0.00%)  0/140 (0.00%)  1/145 (0.69%)  0/144 (0.00%) 
Appendicitis  1  1/1106 (0.09%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Injury, poisoning and procedural complications           
Ankle fracture  1  0/1106 (0.00%)  0/151 (0.00%)  1/140 (0.71%)  0/145 (0.00%)  0/144 (0.00%) 
Hand fracture  1  1/1106 (0.09%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Metabolism and nutrition disorders           
Type 2 diabetes mellitus  1  1/1106 (0.09%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Intraductal proliferative breast lesion  1  0/1106 (0.00%)  0/151 (0.00%)  1/140 (0.71%)  0/145 (0.00%)  0/144 (0.00%) 
Pregnancy, puerperium and perinatal conditions           
Abortion missed  1  1/1106 (0.09%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Psychiatric disorders           
Completed suicide  1 [1]  0/1106 (0.00%)  0/151 (0.00%)  0/140 (0.00%)  1/145 (0.69%)  0/144 (0.00%) 
Suicidal ideation  1  2/1106 (0.18%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Panic attack  1  1/1106 (0.09%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Renal and urinary disorders           
Nephrolithiasis  1  0/1106 (0.00%)  0/151 (0.00%)  0/140 (0.00%)  1/145 (0.69%)  0/144 (0.00%) 
1
Term from vocabulary, MedDRA: 22.0
Indicates events were collected by systematic assessment
[1]
One treatment-emergent death occurred during treatment with vortioxetine 10 mg and was not related.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Open-label: Vortioxetine 10 mg Double-blind: Placebo Double-blind: Vortioxetine 5 mg Double-blind: Vortioxetine 10 mg Double-blind: Vortioxetine 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   417/1106 (37.70%)   16/151 (10.60%)   30/140 (21.43%)   27/145 (18.62%)   32/144 (22.22%) 
Gastrointestinal disorders           
Nausea  1  292/1106 (26.40%)  2/151 (1.32%)  4/140 (2.86%)  5/145 (3.45%)  13/144 (9.03%) 
Dry mouth  1  58/1106 (5.24%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
Infections and infestations           
Upper respiratory tract infection  1  0/1106 (0.00%)  6/151 (3.97%)  9/140 (6.43%)  9/145 (6.21%)  9/144 (6.25%) 
Nasopharyngitis  1  56/1106 (5.06%)  4/151 (2.65%)  7/140 (5.00%)  7/145 (4.83%)  8/144 (5.56%) 
Investigations           
Weight increased  1  0/1106 (0.00%)  3/151 (1.99%)  5/140 (3.57%)  7/145 (4.83%)  8/144 (5.56%) 
Musculoskeletal and connective tissue disorders           
Back pain  1  0/1106 (0.00%)  2/151 (1.32%)  8/140 (5.71%)  0/145 (0.00%)  2/144 (1.39%) 
Nervous system disorders           
Headache  1  91/1106 (8.23%)  0/151 (0.00%)  0/140 (0.00%)  0/145 (0.00%)  0/144 (0.00%) 
1
Term from vocabulary, MedDRA: 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02371980    
Other Study ID Numbers: LuAA21004_402
U1111-1161-4956 ( Registry Identifier: WHO )
First Submitted: February 20, 2015
First Posted: February 26, 2015
Results First Submitted: April 3, 2020
Results First Posted: April 17, 2020
Last Update Posted: April 17, 2020