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Safety and Efficacy of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT01153009
Recruitment Status : Completed
First Posted : June 29, 2010
Results First Posted : December 18, 2013
Last Update Posted : December 18, 2013
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 Depressive Disorder, Major
Interventions Drug: Vortioxetine
Drug: Duloxetine
Drug: Placebo
Enrollment 614
Recruitment Details Participants took part in the study at 58 investigative sites in the United States from 22 June 2010 to 20 March 2012.
Pre-assignment Details Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 4 treatment groups, once a day placebo, 15 mg vortioxetine, 20 mg vortioxetine, or 60 mg duloxetine.
Arm/Group Title Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Hide Arm/Group Description Placebo-matching capsules, orally, once daily for up to 9 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week. Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.
Period Title: Overall Study
Started 161 147 154 152
Treated 159 147 154 150
Completed 129 113 113 115
Not Completed 32 34 41 37
Reason Not Completed
Adverse Event             4             14             14             10
Lack of Efficacy             9             0             2             1
Noncompliance with Study Medication             1             3             4             1
Protocol Deviations             4             3             3             2
Withdrawal of Consent             5             5             4             6
Lost to Follow-up             8             8             11             15
Other             1             1             3             2
Arm/Group Title Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg Total
Hide Arm/Group Description Placebo-matching capsules, orally, once daily for up to 9 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week. Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week. Total of all reporting groups
Overall Number of Baseline Participants 161 147 154 152 614
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
42.4  (12.55) 43.1  (12.28) 42.8  (12.40) 43.4  (12.24) 42.9  (12.35)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
≤55 years 138 125 132 126 521
>55 years 23 22 22 26 93
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
Female
116
  72.0%
104
  70.7%
114
  74.0%
119
  78.3%
453
  73.8%
Male
45
  28.0%
43
  29.3%
40
  26.0%
33
  21.7%
161
  26.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
Hispanic or Latino 18 20 18 23 79
Non-Hispanic and non-Latino 143 127 136 129 535
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
Caucasian (or White, including Hispanic) 122 114 115 119 470
Black 37 31 36 32 136
American Indian or Alaska Native 1 0 0 0 1
Asian 1 2 3 1 7
Native Hawaiian or Other Pacific Islander 0 0 0 0 0
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
161 147 154 152 614
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
168.46  (9.757) 167.23  (8.254) 168.03  (9.530) 166.40  (9.851) 167.55  (9.395)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
88.61  (24.786) 87.42  (21.431) 87.44  (23.806) 87.16  (24.196) 87.67  (23.574)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
31.13  (7.882) 31.26  (7.476) 30.92  (7.633) 31.49  (8.448) 31.20  (7.855)
Waist circumference  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
98.73  (18.232) 96.86  (16.116) 96.47  (18.301) 97.73  (17.971) 97.47  (17.678)
Smoking classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
Never smoked 82 79 73 75 309
Current smoker 46 38 41 39 164
Ex-smoker 33 30 40 38 141
Alcohol consumption  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
Never 61 48 61 67 237
Once monthly or less often 58 55 45 54 212
Once per week 24 23 24 17 88
2 to 6 times per week 16 19 21 14 70
Daily 2 2 3 0 7
Montgomery Åsberg Depression Rating Scale (MADRS) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
31.6  (4.18) 31.9  (4.08) 32.0  (4.36) 32.9  (4.39) 32.1  (4.27)
[1]
Measure Description: The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression).
Hamilton Anxiety Scale Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
17.0  (5.12) 17.5  (5.28) 17.8  (5.42) 18.4  (5.81) 17.7  (5.42)
[1]
Measure Description: Hamilton Anxiety Scale (HAM-A) is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 (absent) to 56 (maximum severity).
Clinical Global Impression - Severity scale score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 161 participants 147 participants 154 participants 152 participants 614 participants
4.6  (0.58) 4.5  (0.55) 4.5  (0.60) 4.5  (0.60) 4.5  (0.58)
[1]
Measure Description: The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis 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; or 7, extremely ill.
1.Primary Outcome
Title Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Hide Description The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.
Time Frame Baseline and Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized patients who received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy. A mixed model for repeated measurements (MMRM) based on observed cases was used.
Arm/Group Title Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.
Overall Number of Participants Analyzed 129 113 112 115
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-12.83  (0.834) -14.30  (0.890) -15.57  (0.880) -16.90  (0.884)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 15 mg
Comments All statistical tests were 2-sided with the estimated P-values at the 5% level of significance. To control for multiplicity, a pre-specified sequential testing procedure was applied to compare 15 mg and 20 mg vortioxetine to placebo. Efficacy endpoints were tested for each dose in a sequential order at significance level 0.025; as soon as an endpoint was non-significant at 0.025, the testing procedure stopped for all subsequent endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.224
Comments Pre-specified sequential statistical testing procedure indicates that when p-value >0.025, hierarchical testing stops for this dose and for subsequent endpoints in the sequence a nominal p-value is provided.
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline MADRS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-3.86 to 0.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.21
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments Pre-specified sequential statistical testing procedure indicates that when p-value <0.025, hierarchical testing continues for this dose.
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline MADRS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-5.12 to -0.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Duloxetine 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline MADRS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-6.46 to -1.69
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.21
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With a MADRS Response at Week 8
Hide Description Response is defined as a participant with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Time Frame Baseline and Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, last observation carried forward was used.
Arm/Group Title Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.
Overall Number of Participants Analyzed 153 145 147 146
Measure Type: Number
Unit of Measure: percentage of participants
39.2 44.1 44.2 54.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.348
Comments [Not Specified]
Method Regression, Logistic
Comments P-value is from logistic regression with explanatory variables for treatment and Baseline MADRS score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.249
Confidence Interval (2-Sided) 95%
0.786 to 1.984
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.332
Comments Pre-specified sequential statistical testing procedure indicates that when p-value >0.025, hierarchical testing stops for this dose and for subsequent endpoints in the sequence a nominal p-value is provided.
Method Regression, Logistic
Comments P-value is from logistic regression with explanatory variables for treatment and Baseline MADRS score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.257
Confidence Interval (2-Sided) 95%
0.792 to 1.994
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Duloxetine 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Regression, Logistic
Comments P-value is from logistic regression with explanatory variables for treatment and Baseline MADRS score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.991
Confidence Interval (2-Sided) 95%
1.250 to 3.171
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Clinical Global Impression Scale - Improvement (CGI-I) Score at Week 8
Hide Description The Clinical Global Impression-Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline Clinical Global Impression Scale-Severity of Illness (CGI-S) score-by-week as fixed effects.
Time Frame Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set. A mixed model for repeated measurements (MMRM) based on observed cases was used.
Arm/Group Title Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.
Overall Number of Participants Analyzed 129 112 111 115
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
2.65  (0.096) 2.54  (0.102) 2.47  (0.101) 2.31  (0.101)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.400
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline CGI-S score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.39 to 0.16
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.140
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline CGI-S score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.46 to 0.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.139
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Duloxetine 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline CGI-S score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.61 to -0.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.139
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥20
Hide Description

The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.

HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56, where lower scores indicate mild severity.

Time Frame Baseline and Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set patients with a HAM-A Baseline score ≥20. A mixed model for repeated measurements (MMRM) based on observed cases was used.
Arm/Group Title Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.
Overall Number of Participants Analyzed 42 44 34 47
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-14.27  (1.676) -13.34  (1.624) -14.89  (1.777) -18.31  (1.573)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.684
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline MADRS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
-3.58 to 5.45
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.286
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.797
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline MADRS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-5.40 to 4.15
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.419
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Duloxetine 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method Mixed model for repeated mesurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline MADRS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.05
Confidence Interval (2-Sided) 95%
-8.54 to 0.45
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.278
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants in MADRS Remission at Week 8
Hide Description Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Time Frame Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, last observation carried forward was used.
Arm/Group Title Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.
Overall Number of Participants Analyzed 153 145 147 146
Measure Type: Number
Unit of Measure: percentage of participants
26.8 26.9 29.3 26.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.845
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression with explanatory variables for treatment and Baseline MADRS score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.053
Confidence Interval (2-Sided) 95%
0.625 to 1.775
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.503
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression with explanatory variables for treatment and Baseline MADRS score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.192
Confidence Interval (2-Sided) 95%
0.713 to 1.994
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Duloxetine 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.728
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression with explanatory variables for treatment and Baseline MADRS score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.098
Confidence Interval (2-Sided) 95%
0.648 to 1.860
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8
Hide Description The Sheehan Disability Scale 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. LS means were from mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline SDS total score-by-week as fixed effects.
Time Frame Baseline and Week 8
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Hide Analysis Population Description
Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases was used.
Arm/Group Title Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week.
Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.
Overall Number of Participants Analyzed 85 77 77 73
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-7.68  (0.776) -7.73  (0.821) -8.55  (0.810) -9.66  (0.834)
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Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.962
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline SDS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-2.24 to 2.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.111
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.427
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline SDS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.88
Confidence Interval (2-Sided) 95%
-3.05 to 1.29
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.103
Estimation Comments [Not Specified]
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Statistical Analysis Overview Comparison Group Selection Placebo, Duloxetine 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method Mixed model for repeated measurements
Comments MMRM ANCOVA with treatment, center, week, treatment-by-week interaction, baseline SDS total score-by-week as fixed effects.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.99
Confidence Interval (2-Sided) 95%
-4.19 to 0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.123
Estimation Comments [Not Specified]
Time Frame A treatment-emergent adverse event is defined as any event whose onset occurs or intensity increases after the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication.
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 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Hide Arm/Group Description Placebo-matching capsules, orally, once daily for up to 9 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 20 mg, encapsulated tablets, orally, once daily for 7 weeks, then placebo-matching capsules, orally, once daily for one week. Duloxetine 30 mg capsules, orally, once daily for one week then duloxetine 60 mg, capsules, orally, once daily for 7 weeks, then duloxetine 30 mg capsules, once daily, for one week.
All-Cause Mortality
Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/159 (0.00%)   2/147 (1.36%)   0/154 (0.00%)   0/150 (0.00%) 
Injury, poisoning and procedural complications         
Stress fracture  1  0/159 (0.00%)  1/147 (0.68%)  0/154 (0.00%)  0/150 (0.00%) 
Psychiatric disorders         
Suicidal ideation  1  0/159 (0.00%)  1/147 (0.68%)  0/154 (0.00%)  0/150 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Vortioxetine 15 mg Vortioxetine 20 mg Duloxetine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   94/159 (59.12%)   101/147 (68.71%)   112/154 (72.73%)   119/150 (79.33%) 
Cardiac disorders         
Palpitations  1  3/159 (1.89%)  3/147 (2.04%)  2/154 (1.30%)  5/150 (3.33%) 
Ear and labyrinth disorders         
Tinnitus  1  2/159 (1.26%)  5/147 (3.40%)  2/154 (1.30%)  1/150 (0.67%) 
Eye disorders         
Vision blurred  1  2/159 (1.26%)  2/147 (1.36%)  2/154 (1.30%)  6/150 (4.00%) 
Gastrointestinal disorders         
Nausea  1  18/159 (11.32%)  52/147 (35.37%)  51/154 (33.12%)  55/150 (36.67%) 
Dry mouth  1  16/159 (10.06%)  14/147 (9.52%)  22/154 (14.29%)  26/150 (17.33%) 
Diarrhoea  1  10/159 (6.29%)  22/147 (14.97%)  12/154 (7.79%)  19/150 (12.67%) 
Constipation  1  10/159 (6.29%)  8/147 (5.44%)  14/154 (9.09%)  18/150 (12.00%) 
Vomiting  1  1/159 (0.63%)  7/147 (4.76%)  13/154 (8.44%)  12/150 (8.00%) 
Dyspepsia  1  3/159 (1.89%)  6/147 (4.08%)  5/154 (3.25%)  7/150 (4.67%) 
Abdominal pain upper  1  0/159 (0.00%)  3/147 (2.04%)  6/154 (3.90%)  4/150 (2.67%) 
Abdominal discomfort  1  4/159 (2.52%)  4/147 (2.72%)  4/154 (2.60%)  1/150 (0.67%) 
Flatulence  1  3/159 (1.89%)  4/147 (2.72%)  2/154 (1.30%)  2/150 (1.33%) 
General disorders         
Fatigue  1  4/159 (2.52%)  7/147 (4.76%)  8/154 (5.19%)  17/150 (11.33%) 
Feeling jittery  1  2/159 (1.26%)  1/147 (0.68%)  2/154 (1.30%)  5/150 (3.33%) 
Irritability  1  1/159 (0.63%)  3/147 (2.04%)  3/154 (1.95%)  4/150 (2.67%) 
Infections and infestations         
Upper respiratory tract infection  1  11/159 (6.92%)  5/147 (3.40%)  8/154 (5.19%)  7/150 (4.67%) 
Nasopharyngitis  1  10/159 (6.29%)  6/147 (4.08%)  9/154 (5.84%)  5/150 (3.33%) 
Viral upper respiratory tract infection  1  4/159 (2.52%)  4/147 (2.72%)  0/154 (0.00%)  5/150 (3.33%) 
Urinary tract infection bacterial  1  0/159 (0.00%)  3/147 (2.04%)  1/154 (0.65%)  4/150 (2.67%) 
Gastroenteritis viral  1  3/159 (1.89%)  1/147 (0.68%)  4/154 (2.60%)  3/150 (2.00%) 
Injury, poisoning and procedural complications         
Fall  1  5/159 (3.14%)  1/147 (0.68%)  1/154 (0.65%)  1/150 (0.67%) 
Muscle strain  1  1/159 (0.63%)  3/147 (2.04%)  1/154 (0.65%)  3/150 (2.00%) 
Investigations         
Heart rate increased  1  0/159 (0.00%)  3/147 (2.04%)  0/154 (0.00%)  0/150 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  4/159 (2.52%)  1/147 (0.68%)  4/154 (2.60%)  15/150 (10.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  2/159 (1.26%)  6/147 (4.08%)  2/154 (1.30%)  1/150 (0.67%) 
Musculoskeletal pain  1  4/159 (2.52%)  4/147 (2.72%)  0/154 (0.00%)  1/150 (0.67%) 
Myalgia  1  2/159 (1.26%)  4/147 (2.72%)  2/154 (1.30%)  1/150 (0.67%) 
Arthralgia  1  3/159 (1.89%)  3/147 (2.04%)  3/154 (1.95%)  0/150 (0.00%) 
Muscle spasms  1  1/159 (0.63%)  3/147 (2.04%)  2/154 (1.30%)  2/150 (1.33%) 
Pain in extremity  1  3/159 (1.89%)  3/147 (2.04%)  0/154 (0.00%)  2/150 (1.33%) 
Nervous system disorders         
Headache  1  21/159 (13.21%)  26/147 (17.69%)  20/154 (12.99%)  28/150 (18.67%) 
Dizziness  1  5/159 (3.14%)  15/147 (10.20%)  20/154 (12.99%)  24/150 (16.00%) 
Somnolence  1  5/159 (3.14%)  3/147 (2.04%)  6/154 (3.90%)  12/150 (8.00%) 
Dysgeusia  1  0/159 (0.00%)  1/147 (0.68%)  1/154 (0.65%)  5/150 (3.33%) 
Sedation  1  2/159 (1.26%)  4/147 (2.72%)  5/154 (3.25%)  3/150 (2.00%) 
Tension headache  1  3/159 (1.89%)  2/147 (1.36%)  4/154 (2.60%)  3/150 (2.00%) 
Poor quality sleep  1  4/159 (2.52%)  0/147 (0.00%)  1/154 (0.65%)  1/150 (0.67%) 
Psychiatric disorders         
Insomnia  1  8/159 (5.03%)  5/147 (3.40%)  13/154 (8.44%)  14/150 (9.33%) 
Abnormal dreams  1  7/159 (4.40%)  7/147 (4.76%)  6/154 (3.90%)  3/150 (2.00%) 
Libido decreased  1  3/159 (1.89%)  1/147 (0.68%)  5/154 (3.25%)  2/150 (1.33%) 
Anxiety  1  4/159 (2.52%)  4/147 (2.72%)  2/154 (1.30%)  4/150 (2.67%) 
Nightmare  1  2/159 (1.26%)  0/147 (0.00%)  0/154 (0.00%)  4/150 (2.67%) 
Restlessness  1  1/159 (0.63%)  0/147 (0.00%)  0/154 (0.00%)  4/150 (2.67%) 
Depression  1  4/159 (2.52%)  0/147 (0.00%)  0/154 (0.00%)  0/150 (0.00%) 
Middle insomnia  1  1/159 (0.63%)  0/147 (0.00%)  0/154 (0.00%)  3/150 (2.00%) 
Nervousness  1  1/159 (0.63%)  1/147 (0.68%)  1/154 (0.65%)  3/150 (2.00%) 
Reproductive system and breast disorders         
Erectile dysfunction  1  0/159 (0.00%)  0/147 (0.00%)  0/154 (0.00%)  3/150 (2.00%) 
Respiratory, thoracic and mediastinal disorders         
Yawning  1  1/159 (0.63%)  0/147 (0.00%)  0/154 (0.00%)  4/150 (2.67%) 
Rhinorrhoea  1  1/159 (0.63%)  2/147 (1.36%)  0/154 (0.00%)  3/150 (2.00%) 
Skin and subcutaneous tissue disorders         
Hyperhidrosis  1  3/159 (1.89%)  1/147 (0.68%)  3/154 (1.95%)  8/150 (5.33%) 
Vascular disorders         
Hot flush  1  1/159 (0.63%)  2/147 (1.36%)  4/154 (2.60%)  2/150 (1.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
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
Name/Title: Medical Director, Clinical Science
Organization: Takeda
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01153009     History of Changes
Other Study ID Numbers: LuAA21004_315
U1111-1114-8191 ( Registry Identifier: WHO )
First Submitted: June 28, 2010
First Posted: June 29, 2010
Results First Submitted: October 25, 2013
Results First Posted: December 18, 2013
Last Update Posted: December 18, 2013