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Trial record 41 of 1323 for:    "Depressive Disorder" [DISEASE] AND Rating AND Major Depressive Disorder AND weeks

A Phase 3 Study of Lu AA21004 in Patients With Major Depressive Disorder

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: NCT02389816
Recruitment Status : Completed
First Posted : March 17, 2015
Results First Posted : June 26, 2019
Last Update Posted : June 27, 2019
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: Placebo
Drug: Vortioxetine
Enrollment 493
Recruitment Details Participants took part in the study at 64 investigative sites in Japan, from 10 April 2015 to 16 March 2018.
Pre-assignment Details Participants with a historical diagnosis of major depressive disorder were enrolled placebo lead-in period for one week prior to randomization, after that participants randomized and enrolled in one of three treatment group (Placebo Group, vortioxetine 10 milligrams (mg) Group, vortioxetine 20 mg Group) for 8 weeks as double-blind treatment period.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description Placebo tablets, orally, once daily for up to Week 8 Vortioxetine 10 mg tablets, orally, once daily for up to Week 8 Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Period Title: Overall Study
Started 164 165 164
Completed 149 152 152
Not Completed 15 13 12
Reason Not Completed
Randomized but Not Treated             1             0             0
Pretreatment Event or Adverse Event (AE)             4             6             7
Major Protocol Deviation             1             0             0
Lost to Follow-up             1             0             0
Withdrawal of Consent             6             4             4
Lack of Efficacy             1             0             0
Non Compliance with Study Drug             1             1             1
Reason not Specified             0             2             0
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg Total
Hide Arm/Group Description Placebo tablets, orally, once daily for up to Week 8 Vortioxetine 10 mg tablets, orally, once daily for up to Week 8 Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8 Total of all reporting groups
Overall Number of Baseline Participants 164 165 164 493
Hide Baseline Analysis Population Description
Randomized Set, Randomized set was defined as all participants who randomized in this study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 164 participants 165 participants 164 participants 493 participants
39.5  (10.47) 40.0  (10.58) 40.4  (11.31) 40.0  (10.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 164 participants 165 participants 164 participants 493 participants
Female
72
  43.9%
72
  43.6%
80
  48.8%
224
  45.4%
Male
92
  56.1%
93
  56.4%
84
  51.2%
269
  54.6%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 164 participants 165 participants 164 participants 493 participants
164 165 164 493
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 164 participants 165 participants 164 participants 493 participants
166.5  (8.51) 165.2  (9.04) 164.5  (7.86) 165.4  (8.51)
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 163 participants 165 participants 164 participants 492 participants
62.44  (12.218) 61.97  (12.958) 61.54  (12.006) 61.98  (12.382)
[1]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Body Mass Index (BMI)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 163 participants 165 participants 164 participants 492 participants
22.44  (3.450) 22.56  (3.560) 22.65  (3.594) 22.55  (3.530)
[1]
Measure Description: BMI = weight (kg)/[height (m)^2]
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Montgomery Åsberg Depression Rating Scale (MADRS) Total Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 163 participants 165 participants 164 participants 492 participants
30.5  (3.87) 30.8  (3.73) 30.6  (3.62) 30.6  (3.73)
[1]
Measure Description: MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms.
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Hamilton Depression Scale (HAM-D17) Total Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 163 participants 165 participants 164 participants 492 participants
22.0  (3.19) 22.1  (3.10) 22.2  (3.10) 22.1  (3.13)
[1]
Measure Description: The HAM-D17 is a clinician-rated scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52 where a higher score indicates a greater depressive state.
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Clinical Global Impressions-Severity (CGI-S) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 163 participants 165 participants 164 participants 492 participants
4.5  (0.63) 4.5  (0.63) 4.5  (0.61) 4.5  (0.62)
[1]
Measure Description: The CGI-S assesses the impression of the participant's current state of mental illness. The current severity of mental illness is rated on a seven-point scale (1=normal, not ill at all ~ 7=most extremely ill) based on a total clinical experience. Higher scores indicate greater severity of mental illness.
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Sheehan Disability Scale (SDS) Total Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 163 participants 165 participants 164 participants 492 participants
13.9  (6.22) 14.0  (6.00) 14.8  (5.47) 14.2  (5.91)
[1]
Measure Description: The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment.
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Digit Symbol Substitution Test (DSST) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 163 participants 163 participants 164 participants 490 participants
60.2  (13.93) 56.8  (15.15) 58.0  (13.72) 58.3  (14.32)
[1]
Measure Description: The DSST is a neuropsychological test to assess cognitive function. Participants are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time for a total possible score of 0 to 133. Higher scores-correct number of symbols reflects greater objective cognitive functioning. An increase in score represents an improvement in an integrated measure of cognitive function.
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Perceived Deficits Questionnaire (PDQ-5) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 163 participants 165 participants 164 participants 492 participants
9.0  (3.54) 9.5  (3.52) 9.7  (3.47) 9.4  (3.52)
[1]
Measure Description: PDQ-5 is a self-administered 5-item questionnaire to assess cognition function, including subscales of attention/concentration, retrospective memory, prospective memory, and planning/organization. PDQ-5 total score ranges from 0 to 20 with smaller scores indicate greater cognitive function.
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
1.Primary Outcome
Title Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Week 8
Hide Description MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.
Time Frame Baseline (At the start of double-blind treatment period), up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-12.37  (0.714) -15.03  (0.699) -15.45  (0.705)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0080
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed Models for Repeated Measures (MMRM)
Method of Estimation Estimation Parameter Least square (LS) mean difference
Estimated Value -2.66
Confidence Interval (2-Sided) 95%
-4.63 to -0.70
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.999
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0023
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed Models for Repeated Measures (MMRM)
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -3.07
Confidence Interval (2-Sided) 95%
-5.05 to -1.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.003
Estimation Comments [Not Specified]
2.Secondary Outcome
Title MADRS Response at Week 8 (Last Observation Carried Forward (LOCF))
Hide Description Reported data was percentage of participants who met MADRS response criteria (defined as a ≥50% decrease in the MADRS total score from Baseline) at Week 8 for each group. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Measure Type: Number
Unit of Measure: Percentage of Participants
36.6 47.9 50.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0341
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.621
Confidence Interval (2-Sided) 95%
1.037 to 2.533
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0110
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.788
Confidence Interval 95%
1.143 to 2.799
Estimation Comments [Not Specified]
3.Secondary Outcome
Title MADRS Remission at Week 8 (LOCF)
Hide Description Reported data was percentage of participants who met MADRS remission criteria (defined as a MADRS total score ≤10) at Week 8 for each group. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Measure Type: Number
Unit of Measure: Percentage of Participants
21.1 32.1 30.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0186
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.839
Confidence Interval (2-Sided) 95%
1.107 to 3.054
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0418
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.700
Confidence Interval (2-Sided) 95%
1.020 to 2.834
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Hamilton Depression Scale (HAM-D17) Total Score to Week 8 (LOCF)
Hide Description The HAM-D17 is a clinician-rated scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52 where a higher score indicates a greater depressive state.
Time Frame Baseline (At the start of double-blind treatment period), up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-8.38  (0.541) -10.19  (0.524) -10.17  (0.532)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0165
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.81
Confidence Interval (2-Sided) 95%
-3.290 to -0.332
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.753
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0190
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.79
Confidence Interval (2-Sided) 95%
-3.278 to -0.295
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.759
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Clinical Global Impressions-Improvement (CGI-I) Score at Week 8 (LOCF)
Hide Description The CGI-I assesses the participant's state of mental illness improvement. The participant's condition compared to baseline is rated on a seven-point scale (1=very much improved ~ 7=very much worse). Higher scores indicate greater worsening of illness. Values closest to 1 for this outcome measure indicate the greatest improvement of symptoms.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
2.77  (0.085) 2.42  (0.084) 2.38  (0.085)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.590 to -0.121
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.120
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.629 to -0.158
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.120
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score to Week 8 (LOCF)
Hide Description The CGI-S assesses the impression of the participant's current state of mental illness. The current severity of mental illness is rated on a seven-point scale (1=normal, not ill at all ~ 7=most extremely ill) based on a total clinical experience. Higher scores indicate greater severity of mental illness.
Time Frame Baseline (At the start of double-blind treatment period), up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-1.19  (0.0088) -1.42  (0.0087) -1.48  (0.0087)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0609
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.474 to 0.011
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.123
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0179
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.537 to -0.051
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.124
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Sheehan Disability Scale (SDS) Total Score to Week 8 (LOCF)
Hide Description The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment.
Time Frame Baseline (At the start of double-blind treatment period), up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-2.85  (0.447) -4.20  (0.432) -4.43  (0.440)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0311
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.34
Confidence Interval (2-Sided) 95%
-2.564 to -0.122
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.621
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0126
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.57
Confidence Interval (2-Sided) 95%
-2.807 to -0.339
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.628
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Digit Symbol Substitution Test (DSST) Total Score to Week 8 (LOCF)
Hide Description The DSST is a neuropsychological test to assess cognitive function. Participants are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time for a total possible score of 0 to 133. Higher scores-correct number of symbols reflects greater objective cognitive functioning. An increase in score represents an improvement in an integrated measure of cognitive function.
Time Frame Baseline (At the start of double-blind treatment period), up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
4.92  (0.632) 4.13  (0.628) 4.80  (0.629)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3793
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.79
Confidence Interval (2-Sided) 95%
-2.539 to 0.968
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.893
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9011
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-1.862 to 1.641
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.891
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Perceived Deficits Questionnaire (PDQ-5) Total Score to Week 8 (LOCF)
Hide Description PDQ-5 is a self-administered 5-item questionnaire to assess cognition function, including subscales of attention/concentration, retrospective memory, prospective memory, and planning/organization. PDQ-5 total score ranges from 0 to 20 with smaller scores indicate greater cognitive function.
Time Frame Baseline (At the start of double-blind treatment period), up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description:
Placebo tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 8
Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Number of Participants Analyzed 164 165 164
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-1.41  (0.234) -2.28  (0.231) -2.69  (0.234)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0089
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.87
Confidence Interval (2-Sided) 95%
-1.512 to -0.218
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.329
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.27
Confidence Interval (2-Sided) 95%
-1.922 to -0.619
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.332
Estimation Comments [Not Specified]
Time Frame Up to Week 12
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 Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description Placebo tablets, orally, once daily for up to Week 8 Vortioxetine 10 mg tablets, orally, once daily for up to Week 8 Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
All-Cause Mortality
Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/161 (0.00%)   0/165 (0.00%)   2/163 (1.23%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/161 (0.62%)   1/165 (0.61%)   3/163 (1.84%) 
Injury, poisoning and procedural complications       
Anaesthetic complication  1  0/161 (0.00%)  0/165 (0.00%)  1/163 (0.61%) 
Subarachnoid haemorrhage  1  0/161 (0.00%)  0/165 (0.00%)  1/163 (0.61%) 
Nervous system disorders       
Altered state of consciousness  1  0/161 (0.00%)  1/165 (0.61%)  0/163 (0.00%) 
Cerebral haemorrhage  1  0/161 (0.00%)  0/165 (0.00%)  1/163 (0.61%) 
Renal and urinary disorders       
Nephrolithiasis  1  1/161 (0.62%)  0/165 (0.00%)  0/163 (0.00%) 
1
Term from vocabulary, MedDRA/J (Ver. 21.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/161 (19.88%)   54/165 (32.73%)   51/163 (31.29%) 
Gastrointestinal disorders       
Nausea  1  1/161 (0.62%)  21/165 (12.73%)  25/163 (15.34%) 
Vomiting  1  0/161 (0.00%)  9/165 (5.45%)  6/163 (3.68%) 
Infections and infestations       
Nasopharyngitis  1  26/161 (16.15%)  23/165 (13.94%)  21/163 (12.88%) 
Nervous system disorders       
Somnolence  1  6/161 (3.73%)  7/165 (4.24%)  11/163 (6.75%) 
1
Term from vocabulary, MedDRA/J (Ver. 21.0)
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: NCT02389816     History of Changes
Other Study ID Numbers: LuAA21004/CCT-004
U1111-1167-1520 ( Registry Identifier: WHO )
JapicCTI-152831 ( Registry Identifier: JapicCTI )
First Submitted: March 10, 2015
First Posted: March 17, 2015
Results First Submitted: March 15, 2019
Results First Posted: June 26, 2019
Last Update Posted: June 27, 2019