ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy Study of Vortioxetine (Lu AA21004) in Adults 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: NCT01179516
Recruitment Status : Completed
First Posted : August 11, 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: Placebo
Enrollment 469

Recruitment Details Participants took part in the study at 65 investigative sites in the United States from 11 August 2010 to 04 June 2012.
Pre-assignment Details Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 3 treatment groups, once a day placebo, 10 mg, or 15 mg vortioxetine.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 15 mg
Hide Arm/Group Description Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Period Title: Overall Study
Started 160 157 152
Treated 160 154 151
Completed 133 131 121
Not Completed 27 26 31
Reason Not Completed
Pretreatment Event or Adverse Event             6             8             12
Lack of Efficacy             4             2             0
Noncompliance with Study Drug             2             0             1
Protocol Deviations             4             3             3
Withdrawal of Consent             2             6             10
Lost to Follow-up             7             7             3
Other             2             0             2
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 15 mg Total
Hide Arm/Group Description Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks. Total of all reporting groups
Overall Number of Baseline Participants 160 157 152 469
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 160 participants 157 participants 152 participants 469 participants
46.2  (11.79) 45.2  (11.94) 43.8  (13.51) 45.1  (12.44)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 160 participants 157 participants 152 participants 469 participants
≤55 years 122 129 120 371
>55 years 38 28 32 98
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 157 participants 152 participants 469 participants
Female
108
  67.5%
113
  72.0%
108
  71.1%
329
  70.1%
Male
52
  32.5%
44
  28.0%
44
  28.9%
140
  29.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 160 participants 157 participants 152 participants 469 participants
Hispanic or Latino 20 16 18 54
Non-Hispanic and non-Latino 140 141 134 415
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 160 participants 157 participants 152 participants 469 participants
Caucasian (White, including Hispanic) 124 115 109 348
Black 35 39 38 112
Asian 1 1 4 6
American Indian or Alaska Native 0 2 1 3
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 160 participants 157 participants 152 participants 469 participants
160 157 152 469
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 160 participants 157 participants 152 participants 469 participants
168.85  (10.407) 167.35  (9.523) 167.52  (9.789) 167.92  (9.920)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 160 participants 157 participants 152 participants 469 participants
89.14  (24.010) 87.74  (23.914) 86.49  (23.154) 87.81  (23.678)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 160 participants 157 participants 152 participants 469 participants
31.14  (7.533) 31.29  (8.063) 30.78  (7.752) 31.07  (7.771)
Waist Circumference  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 160 participants 157 participants 152 participants 469 participants
99.93  (17.820) 100.02  (16.762) 97.93  (17.536) 99.31  (17.370)
Smoking Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 160 participants 157 participants 152 participants 469 participants
Never smoked 83 86 62 231
Current smoker 46 40 52 138
Ex-smoker 31 31 38 100
Alcohol Consumption  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 160 participants 157 participants 152 participants 469 participants
Never 49 54 51 154
Once monthly or less often 60 56 62 178
Once per week 26 20 21 67
2 to 6 times per week 24 22 14 60
Daily 1 5 4 10
Montgomery Åsberg Depression Rating Scale (MADRS) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 160 participants 157 participants 152 participants 469 participants
33.4  (4.53) 34.1  (4.07) 33.7  (4.51) 33.7  (4.37)
[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 160 participants 157 participants 152 participants 469 participants
20.0  (6.14) 20.1  (5.77) 19.5  (5.42) 19.9  (5.78)
[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:  Sores on a scale
Number Analyzed 160 participants 157 participants 152 participants 469 participants
4.7  (0.61) 4.7  (0.56) 4.6  (0.59) 4.7  (0.59)
[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 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 10 mg Vortioxetine 15 mg
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 126 123 113
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-12.87  (1.043) -13.66  (1.064) -13.36  (1.087)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 10 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 for each dose was applied to compare 10 mg and 15 mg vortioxetine to placebo. Efficacy endpoints were tested for each dose in 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 0.597
Comments Pre-specified sequential statistical testing procedure indicates that when p-value >0.025, hierarchical testing stops 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 -0.79
Confidence Interval (2-Sided) 95%
-3.71 to 2.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.488
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.745
Comments Pre-specified sequential statistical testing procedure indicates that when p-value >0.025, hierarchical testing stops 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 -0.49
Confidence Interval (2-Sided) 95%
-3.44 to 2.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.501
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 10 mg Vortioxetine 15 mg
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 149 143 142
Measure Type: Number
Unit of Measure: percentage of participants
32.9 37.8 37.3
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.396
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 1.232
Confidence Interval (2-Sided) 95%
0.761 to 1.995
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.435
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 1.212
Confidence Interval (2-Sided) 95%
0.748 to 1.963
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 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 10 mg Vortioxetine 15 mg
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 127 123 114
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
2.65  (0.105) 2.56  (0.107) 2.60  (0.110)
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.554
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 -0.09
Confidence Interval (2-Sided) 95%
-0.38 to 0.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.149
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.739
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 -0.05
Confidence Interval (2-Sided) 95%
-0.35 to 0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.151
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 10 mg Vortioxetine 15 mg
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 60 57 56
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-14.11  (1.611) -15.07  (1.650) -12.37  (1.689)
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.670
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 -0.97
Confidence Interval (2-Sided) 95%
-5.43 to 3.50
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.261
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.451
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 1.73
Confidence Interval (2-Sided) 95%
-2.80 to 6.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.295
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 10 mg Vortioxetine 15 mg
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 149 143 142
Measure Type: Number
Unit of Measure: percentage of participants
22.1 26.6 23.9
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.352
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression with explanatory variables for treatment and Baseline MADRS total score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.291
Confidence Interval (2-Sided) 95%
0.754 to 2.211
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.694
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression with explanatory variables for treatment and Baseline MADRS total score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.116
Confidence Interval (2-Sided) 95%
0.646 to 1.928
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Sheehan Disability Scale (SDS) Total Score
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
Show Outcome Measure DataHide Outcome Measure Data
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 10 mg Vortioxetine 15 mg
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 77 74 62
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-9.38  (0.877) -10.30  (0.959) -8.69  (0.990)
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.464
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 -0.92
Confidence Interval (2-Sided) 95%
-3.38 to 1.55
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.250
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
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 0.600
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 0.69
Confidence Interval (2-Sided) 95%
-1.91 to 3.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.322
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 10 mg Vortioxetine 15 mg
Hide Arm/Group Description Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks. Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week, then vortioxetine 15 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
All-Cause Mortality
Placebo Vortioxetine 10 mg Vortioxetine 15 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Vortioxetine 10 mg Vortioxetine 15 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/160 (0.63%)   1/154 (0.65%)   0/151 (0.00%) 
Nervous system disorders       
Lumbar radiculopathy  1  1/160 (0.63%)  0/154 (0.00%)  0/151 (0.00%) 
Psychiatric disorders       
Suicidal ideation  1  0/160 (0.00%)  1/154 (0.65%)  0/151 (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 10 mg Vortioxetine 15 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   92/160 (57.50%)   99/154 (64.29%)   96/151 (63.58%) 
Eye disorders       
Vision blurred  1  1/160 (0.63%)  1/154 (0.65%)  4/151 (2.65%) 
Gastrointestinal disorders       
Nausea  1  17/160 (10.63%)  47/154 (30.52%)  51/151 (33.77%) 
Dry mouth  1  11/160 (6.88%)  24/154 (15.58%)  8/151 (5.30%) 
Vomiting  1  4/160 (2.50%)  7/154 (4.55%)  18/151 (11.92%) 
Constipation  1  6/160 (3.75%)  16/154 (10.39%)  14/151 (9.27%) 
Diarrhoea  1  10/160 (6.25%)  10/154 (6.49%)  15/151 (9.93%) 
Flatulence  1  4/160 (2.50%)  10/154 (6.49%)  5/151 (3.31%) 
Dyspepsia  1  5/160 (3.13%)  3/154 (1.95%)  3/151 (1.99%) 
General disorders       
Fatigue  1  8/160 (5.00%)  5/154 (3.25%)  4/151 (2.65%) 
Irritability  1  5/160 (3.13%)  2/154 (1.30%)  2/151 (1.32%) 
Pain  1  4/160 (2.50%)  1/154 (0.65%)  1/151 (0.66%) 
Infections and infestations       
Nasopharyngitis  1  8/160 (5.00%)  6/154 (3.90%)  3/151 (1.99%) 
Influenza  1  7/160 (4.38%)  3/154 (1.95%)  1/151 (0.66%) 
Viral upper respiratory tract infection  1  7/160 (4.38%)  5/154 (3.25%)  3/151 (1.99%) 
Upper respiratory tract infection  1  5/160 (3.13%)  2/154 (1.30%)  3/151 (1.99%) 
Bronchitis  1  4/160 (2.50%)  0/154 (0.00%)  2/151 (1.32%) 
Injury, poisoning and procedural complications       
Muscle strain  1  6/160 (3.75%)  0/154 (0.00%)  1/151 (0.66%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/160 (0.00%)  2/154 (1.30%)  6/151 (3.97%) 
Myalgia  1  4/160 (2.50%)  2/154 (1.30%)  2/151 (1.32%) 
Nervous system disorders       
Headache  1  29/160 (18.13%)  24/154 (15.58%)  25/151 (16.56%) 
Dizziness  1  15/160 (9.38%)  6/154 (3.90%)  12/151 (7.95%) 
Tension headache  1  3/160 (1.88%)  7/154 (4.55%)  3/151 (1.99%) 
Somnolence  1  2/160 (1.25%)  4/154 (2.60%)  6/151 (3.97%) 
Psychiatric disorders       
Insomnia  1  4/160 (2.50%)  4/154 (2.60%)  6/151 (3.97%) 
Anxiety  1  1/160 (0.63%)  1/154 (0.65%)  4/151 (2.65%) 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  4/160 (2.50%)  0/154 (0.00%)  4/151 (2.65%) 
Vascular disorders       
Hot flush  1  6/160 (3.75%)  0/154 (0.00%)  1/151 (0.66%) 
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01179516     History of Changes
Other Study ID Numbers: LuAA21004_317
U1111-1116-3223 ( Registry Identifier: WHO )
SU-06032011-7846 ( Registry Identifier: SMCTD )
First Submitted: August 9, 2010
First Posted: August 11, 2010
Results First Submitted: October 25, 2013
Results First Posted: December 18, 2013
Last Update Posted: December 18, 2013