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

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ClinicalTrials.gov Identifier: NCT01163266
Recruitment Status : Completed
First Posted : July 15, 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 462
Recruitment Details Participants took part in the study at 37 investigative sites in the United States from 15 July 2010 to 17 January 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 20 mg vortioxetine.
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Hide Arm/Group Description 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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Period Title: Overall Study
Started 157 155 150
Treated 157 155 150
Completed 139 124 122
Not Completed 18 31 28
Reason Not Completed
Pretreatment Event or Adverse Event             2             9             7
Lack of Efficacy             1             3             1
Noncompliance with Study Drug             0             2             0
Protocol Deviations             2             2             5
Withdrawal of Consent             5             7             3
Lost to Follow-up             7             7             10
Other             1             1             2
Arm/Group Title Placebo Vortioxetine 10 mg Vortioxetine 20 mg Total
Hide Arm/Group Description 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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks. Total of all reporting groups
Overall Number of Baseline Participants 157 155 150 462
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 157 participants 155 participants 150 participants 462 participants
42.3  (11.61) 43.1  (12.04) 43.1  (13.09) 42.8  (12.23)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 157 participants 155 participants 150 participants 462 participants
≤55 years 130 133 124 387
>55 years 27 22 26 75
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 155 participants 150 participants 462 participants
Female
110
  70.1%
118
  76.1%
107
  71.3%
335
  72.5%
Male
47
  29.9%
37
  23.9%
43
  28.7%
127
  27.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 157 participants 155 participants 150 participants 462 participants
Hispanic or Latino 17 10 10 37
Non-Hispanic and non-Latino 140 145 140 425
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 157 participants 155 participants 150 participants 462 participants
Caucasian (White, including Hispanic) 120 106 97 323
Black 37 43 49 129
American Indian or Alaska Native 0 4 1 5
Asian 0 2 1 3
Native Hawaiian or Other Pacific Islander 0 0 2 2
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 157 participants 155 participants 150 participants 462 participants
157 155 150 462
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 157 participants 155 participants 150 participants 462 participants
167.46  (9.265) 166.86  (9.199) 167.92  (9.194) 167.41  (9.210)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 157 participants 155 participants 150 participants 462 participants
88.28  (23.290) 89.00  (23.076) 87.08  (23.582) 88.13  (23.277)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 157 participants 155 participants 150 participants 462 participants
31.31  (7.262) 31.92  (7.779) 30.84  (7.836) 31.36  (7.622)
Waist Circumference  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 157 participants 155 participants 150 participants 462 participants
100.20  (18.640) 99.76  (16.996) 96.76  (16.434) 98.93  (17.426)
Smoking Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 157 participants 155 participants 150 participants 462 participants
Never smoked 65 82 77 224
Current smoker 52 46 45 143
Ex-smoker 40 27 28 95
Alcohol Consumption  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 157 participants 155 participants 150 participants 462 participants
Never 54 63 52 169
Once monthly or less often 63 47 65 175
Once per week 22 21 19 62
2-to-6 times per week 15 21 14 50
Daily 3 3 0 6
Montgomery Åsberg Depression Rating Scale (MADRS) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 157 participants 155 participants 150 participants 462 participants
32.0  (3.99) 32.3  (4.52) 32.4  (4.30) 32.2  (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 157 participants 155 participants 150 participants 462 participants
17.8  (5.41) 18.5  (5.25) 18.9  (5.64) 18.4  (5.44)
[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 157 participants 155 participants 150 participants 462 participants
4.5  (0.55) 4.5  (0.55) 4.5  (0.54) 4.5  (0.55)
[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 postbaseline 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 20 mg
Hide Arm/Group Description:
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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 139 124 122
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-10.77  (0.807) -12.96  (0.832) -14.41  (0.845)
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 was applied to compare 10 mg and 20 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 0.058
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 -2.19
Confidence Interval (2-Sided) 95%
-4.45 to 0.08
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.151
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 0.002
Comments Pre-specified sequential statistical testing procedure indicates that when p-value <0.025, hierarchical testing continues.
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 -3.64
Confidence Interval (2-Sided) 95%
-5.92 to -1.35
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.161
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 20 mg
Hide Arm/Group Description:
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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 155 154 148
Measure Type: Number
Unit of Measure: percentage of participants
28.4 33.8 39.2
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 0.301
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 1.290
Confidence Interval (2-Sided) 95%
0.796 to 2.093
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 0.044
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 Regression, Logistic
Comments Logistic regression with explanatory variables for treatment and Baseline MADRS score.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.639
Confidence Interval (2-Sided) 95%
1.013 to 2.652
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 Scale (CGI-S) score-by-week as fixed effects.
Time Frame 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 20 mg
Hide Arm/Group Description:
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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 139 124 122
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
2.89  (0.090) 2.69  (0.093) 2.59  (0.094)
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 0.119
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 -0.20
Confidence Interval (2-Sided) 95%
-0.45 to 0.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.129
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 0.024
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 -0.29
Confidence Interval (2-Sided) 95%
-0.55 to -0.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.129
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.

The 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 20 mg
Hide Arm/Group Description:
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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 52 52 57
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-10.26  (1.392) -14.55  (1.369) -17.52  (1.331)
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 0.025
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 -4.29
Confidence Interval (2-Sided) 95%
-8.03 to -0.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.891
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 <0.001
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 -7.26
Confidence Interval (2-Sided) 95%
-10.92 to -3.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.852
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 20 mg
Hide Arm/Group Description:
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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 155 154 148
Measure Type: Number
Unit of Measure: percentage of participants
14.2 21.4 22.3
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 0.093
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 1.665
Confidence Interval (2-Sided) 95%
0.918 to 3.018
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 0.059
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 1.779
Confidence Interval (2-Sided) 95%
0.979 to 3.233
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
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 20 mg
Hide Arm/Group Description:
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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Overall Number of Participants Analyzed 86 89 77
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-5.86  (0.771) -7.25  (0.747) -8.26  (0.794)
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 0.183
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 -1.39
Confidence Interval (2-Sided) 95%
-3.44 to 0.66
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.042
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 0.025
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 -2.40
Confidence Interval (2-Sided) 95%
-4.50 to -0.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.066
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 20 mg
Hide Arm/Group Description 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 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
All-Cause Mortality
Placebo Vortioxetine 10 mg Vortioxetine 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
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   0/157 (0.00%)   2/155 (1.29%)   0/150 (0.00%) 
Infections and infestations       
Kidney infection  1  0/157 (0.00%)  1/155 (0.65%)  0/150 (0.00%) 
Psychiatric disorders       
Suicide attempt  1  0/157 (0.00%)  1/155 (0.65%)  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 10 mg Vortioxetine 20 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   80/157 (50.96%)   103/155 (66.45%)   94/150 (62.67%) 
Ear and labyrinth disorders       
Tinnitus  1  4/157 (2.55%)  1/155 (0.65%)  1/150 (0.67%) 
Eye disorders       
Vision blurred  1  4/157 (2.55%)  1/155 (0.65%)  2/150 (1.33%) 
Gastrointestinal disorders       
Nausea  1  8/157 (5.10%)  42/155 (27.10%)  44/150 (29.33%) 
Diarrhoea  1  14/157 (8.92%)  20/155 (12.90%)  11/150 (7.33%) 
Dry mouth  1  15/157 (9.55%)  7/155 (4.52%)  7/150 (4.67%) 
Constipation  1  4/157 (2.55%)  12/155 (7.74%)  9/150 (6.00%) 
Vomiting  1  3/157 (1.91%)  9/155 (5.81%)  8/150 (5.33%) 
Dyspepsia  1  6/157 (3.82%)  7/155 (4.52%)  4/150 (2.67%) 
Gastrooesophageal reflux disease  1  0/157 (0.00%)  4/155 (2.58%)  1/150 (0.67%) 
Abdominal discomfort  1  2/157 (1.27%)  0/155 (0.00%)  3/150 (2.00%) 
Abdominal distension  1  0/157 (0.00%)  2/155 (1.29%)  3/150 (2.00%) 
Abdominal pain upper  1  3/157 (1.91%)  1/155 (0.65%)  3/150 (2.00%) 
General disorders       
Fatigue  1  9/157 (5.73%)  9/155 (5.81%)  0/150 (0.00%) 
Irritability  1  2/157 (1.27%)  2/155 (1.29%)  3/150 (2.00%) 
Infections and infestations       
Viral upper respiratory tract infection  1  9/157 (5.73%)  10/155 (6.45%)  5/150 (3.33%) 
Nasopharyngitis  1  1/157 (0.64%)  4/155 (2.58%)  7/150 (4.67%) 
Upper respiratory tract infection  1  6/157 (3.82%)  6/155 (3.87%)  3/150 (2.00%) 
Gastroenteritis viral  1  3/157 (1.91%)  5/155 (3.23%)  2/150 (1.33%) 
Sinusitis  1  0/157 (0.00%)  4/155 (2.58%)  1/150 (0.67%) 
Injury, poisoning and procedural complications       
Fall  1  0/157 (0.00%)  4/155 (2.58%)  3/150 (2.00%) 
Ligament sprain  1  1/157 (0.64%)  1/155 (0.65%)  3/150 (2.00%) 
Muscle strain  1  0/157 (0.00%)  0/155 (0.00%)  3/150 (2.00%) 
Road traffic accident  1  0/157 (0.00%)  1/155 (0.65%)  3/150 (2.00%) 
Metabolism and nutrition disorders       
Increased appetite  1  3/157 (1.91%)  1/155 (0.65%)  4/150 (2.67%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  4/157 (2.55%)  3/155 (1.94%)  4/150 (2.67%) 
Back pain  1  2/157 (1.27%)  3/155 (1.94%)  4/150 (2.67%) 
Myalgia  1  4/157 (2.55%)  3/155 (1.94%)  3/150 (2.00%) 
Musculoskeletal pain  1  0/157 (0.00%)  3/155 (1.94%)  3/150 (2.00%) 
Nervous system disorders       
Headache  1  17/157 (10.83%)  24/155 (15.48%)  24/150 (16.00%) 
Dizziness  1  9/157 (5.73%)  13/155 (8.39%)  9/150 (6.00%) 
Somnolence  1  5/157 (3.18%)  7/155 (4.52%)  7/150 (4.67%) 
Tension headache  1  7/157 (4.46%)  3/155 (1.94%)  3/150 (2.00%) 
Dysgeusia  1  0/157 (0.00%)  1/155 (0.65%)  4/150 (2.67%) 
Psychiatric disorders       
Abnormal dreams  1  2/157 (1.27%)  4/155 (2.58%)  6/150 (4.00%) 
Insomnia  1  6/157 (3.82%)  6/155 (3.87%)  3/150 (2.00%) 
Anxiety  1  4/157 (2.55%)  2/155 (1.29%)  0/150 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Nasal congestion  1  4/157 (2.55%)  0/155 (0.00%)  2/150 (1.33%) 
Skin and subcutaneous tissue disorders       
Pruritus generalised  1  3/157 (1.91%)  4/155 (2.58%)  5/150 (3.33%) 
Pruritus  1  1/157 (0.64%)  2/155 (1.29%)  3/150 (2.00%) 
Vascular disorders       
Hypertension  1  1/157 (0.64%)  1/155 (0.65%)  4/150 (2.67%) 
Hot flush  1  1/157 (0.64%)  2/155 (1.29%)  3/150 (2.00%) 
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: NCT01163266     History of Changes
Other Study ID Numbers: LuAA21004_316
U1111-1115-8770 ( Registry Identifier: WHO )
First Submitted: July 14, 2010
First Posted: July 15, 2010
Results First Submitted: October 25, 2013
Results First Posted: December 18, 2013
Last Update Posted: December 18, 2013