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Efficacy of Lu AA21004 on Cognitive Dysfunction in Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT01564862
Recruitment Status : Completed
First Posted : March 28, 2012
Results First Posted : February 5, 2015
Last Update Posted : February 5, 2015
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 (Lu AA21004)
Drug: Duloxetine
Drug: Placebo
Enrollment 602
Recruitment Details Participants took part in the study at 80 investigative sites in Bulgaria, Finland, Germany, Poland, Russia Federation, Ukraine.and the United States from 09 April 2012 to 05 February 2014
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 to 20 mg flexible dose of vortioxetine, or 60 mg duloxetine.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period. Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Period Title: Overall Study
Started 198 210 194
Received Treatment 196 207 191
Completed 168 176 164
Not Completed 30 34 30
Reason Not Completed
Pretreatment Event or Adverse Event             6             12             6
Major Protocol Deviation             3             3             4
Lost to Follow-up             10             8             6
Voluntary Withdrawal             9             6             8
Lack of Efficacy             1             5             6
Other reason(s)             1             0             0
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo Total
Hide Arm/Group Description Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period. Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period). Total of all reporting groups
Overall Number of Baseline Participants 198 210 194 602
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 198 participants 210 participants 194 participants 602 participants
44.2  (12.21) 45.7  (11.46) 45.0  (12.07) 45.0  (11.90)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 198 participants 210 participants 194 participants 602 participants
≤ 55 years 158 164 152 474
> 55 years 40 46 42 128
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 198 participants 210 participants 194 participants 602 participants
Female
135
  68.2%
138
  65.7%
119
  61.3%
392
  65.1%
Male
63
  31.8%
72
  34.3%
75
  38.7%
210
  34.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 198 participants 210 participants 194 participants 602 participants
Hispanic or Latino 8 7 15 30
Non-Hispanic and Non- Latino 90 104 82 276
Not-Specified 100 99 97 296
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 198 participants 210 participants 194 participants 602 participants
Caucasian (or White, including Hispanic) 169 176 171 516
Black 28 27 20 75
Asian 1 6 1 8
American Indian or Alaska Native 0 1 2 3
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 198 participants 210 participants 194 participants 602 participants
168.2  (9.17) 169.7  (9.14) 169.0  (9.43) 169.0  (9.25)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 198 participants 210 participants 194 participants 602 participants
81.84  (22.068) 81.68  (20.965) 80.96  (20.316) 81.50  (21.099)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 198 participants 210 participants 194 participants 602 participants
28.86  (7.334) 28.39  (7.312) 28.27  (6.354) 28.51  (7.018)
Smoking Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 198 participants 210 participants 194 participants 602 participants
Never Smoked 95 109 105 309
Current Smoker 73 68 56 197
Past Smoker 30 33 33 96
Alcohol Consumption  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 198 participants 210 participants 194 participants 602 participants
Never 89 84 87 260
Once Monthly or Less Often 67 73 51 191
Once a Week 23 31 29 83
2 to 6 Times per Week 15 19 24 58
Daily 4 3 3 10
1.Primary Outcome
Title Change From Baseline to Week 8 in the Digit Symbol Substitution Test (DSST)
Hide Description The DSST assesses relative contributions of speed, memory, executive function and visual scanning. Participants are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time for a total possible score of 0 to 133. Higher scores-correct number of symbols reflects greater objective cognitive functioning. An increase in score represents an improvement in an integrated measure of cognitive function. An Analysis of Covariance (ANCOVA) model was used with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy. Participants with scores of > 70 at Baseline were excluded.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 187 167
Least Squares Mean (Standard Error)
Unit of Measure: Correct symbols
4.60  (0.530) 4.06  (0.511) 2.85  (0.542)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine (Lu AA21004), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments P-value was from an ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.75
Confidence Interval (2-Sided) 95%
0.28 to 3.21
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.744
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.099
Comments P-value was from an ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
-0.23 to 2.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.733
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Vortioxetine (Lu AA21004), Duloxetine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.460
Comments P-value was from an ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
-0.89 to 1.96
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.725
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 8 in the Perceived Deficits Questionnaire (PDQ) Attention/Concentration and Planning/Organization Subscore
Hide Description PDQ is a patient-rated scale designed to subjectively assess cognitive dysfunction, comprising four 5-item subscales: Attention/Concentration, Retrospective Memory, Prospective Memory, and Planning/Organization for a total possible score of 0 to 40. The subscale Attention/Concentration is the sum of items 1, 5, 9, 13, and 17 with a range of 0-20; while the subscale Planning/Organization is the sum of items 4, 8, 12, 16, and 20 with the score range of 0 to 20. The scores of the subscales Attention/Concentration and Planning/Organization were summed. Higher scores reflect greater participant-perceived cognitive dysfunction in the domains identified. A decrease in score represents an improvement in subjective cognitive function in the domains identified. A Mixed Model Repeated Measures (MMRM) model was used with baseline*week, center, week, treatment and week*treatment as factors in the analysis.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy,with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 169 179 160
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-8.9  (0.55) -9.3  (0.53) -6.3  (0.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine (Lu AA21004), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments P-value was from a MMRM model with baseline*week, center, week, treatment and week*treatment as factors in the analysis.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-4.1 to -1.0
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value was from a MMRM model with baseline*week, center, week, treatment and week*treatment as factors in the analysis.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-4.5 to -1.5
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.77
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Clinical Global Impressions-Improvement (CGI-I) Score at Week 8
Hide Description The CGI-I assesses the clinician's impression of the subject's state of mental illness improvement and consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on a seven-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change relative to baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater worsening of illness. Values closest to 1 for this outcome measure indicate the greatest improvement of symptoms. A MMRM model was used with baseline*week, center, week, treatment and week*treatment as factors in the analysis.
Time Frame Baseline, Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 169 179 161
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
2.349  (0.0852) 2.235  (0.0826) 2.639  (0.0872)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vortioxetine (Lu AA21004), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments P-value was from a MMRM model with baseline*week, center, week, treatment and week*treatment as factors in the analysis.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value -0.290
Confidence Interval (2-Sided) 95%
-0.528 to -0.052
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1211
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value was from a MMRM model with baseline*week, center, week, treatment and week*treatment as factors in the analysis.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.404
Confidence Interval (2-Sided) 95%
-0.638 to -0.169
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1194
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Week 8 in the Trail Making Test (TMT-A)
Hide Description The TMT is a two-part cognitive test. TMT-A assesses cognitive processing speed and consists of 25 circles distributed over a sheet of paper. Participants have 4 minutes to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Tester informs participant immediately whenever they make an error and allows for corrections by participants. Lower scores represent better speed of processing. A decrease in score over the study represents an improvement in speed in processing. An ANCOVA model was used with treatment and center as fixed factors and the baseline value as a covariate.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 173 180 162
Least Squares Mean (Standard Error)
Unit of Measure: seconds
-7.70  (0.980) -8.06  (0.955) -6.65  (1.009)
5.Secondary Outcome
Title Change From Baseline to Week 8 in the Trail Making Test B (TMT-B)
Hide Description The TMT is a two-part cognitive test. TMT-B assesses executive functioning and consists of 25 circles distributed over a sheet of paper. Participants have 4 minutes to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Tester informs participant immediately whenever they make an error and allows for corrections by participants. Lower score for TMT-B represents better executive function. A decrease in score over the study represents an improvement in executive function. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 157 170 157
Least Squares Mean (Standard Error)
Unit of Measure: seconds
-18.73  (2.096) -14.60  (2.011) -9.06  (2.101)
6.Secondary Outcome
Title Change in Time From Baseline to Week 8 in the Stroop Test
Hide Description The STROOP test assesses the ability to inhibit a prepotent response to reading words while performing a task that requires attention control. It comprises of 2 sheets with 50 words each, up to 50 correct responses for each of the congruent and incongruent Stroop tests. Participants have 4 minutes to name the ink color of each word. Lower time to complete the test indicates better performance. Higher number of correct responses indicates better responses. A decrease in the time to complete the tests and an increase in the number of correct responses both indicate improvement over the course of the study. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 187 167
Mean (Standard Deviation)
Unit of Measure: seconds
Congruent (n=174,187,167) -3.30  (1.086) -4.54  (1.044) -4.37  (1.105)
Incongruent (n=172,186,166) -8.17  (1.560) -9.83  (1.498) -8.11  (1.586)
7.Secondary Outcome
Title Change From Baseline to Week 8 in the Groton Maze Learning Test (GMLT)
Hide Description

The GMLT measures executive functioning and spatial problem solving. Participants learn a hidden pathway through a maze of 10 x 10 grid of tiles on a computer touch screen using step-by-step guess, with trial and error feedback after each step. Once the pathway is learned, participants repeat the same pathway four more times. It usually takes 5-6 minutes to administer this test. Lower score equals better performance. A decrease in score over the course of the study indicates improved executive function.

An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.

Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 169 179 159
Least Squares Mean (Standard Error)
Unit of Measure: Errors
-5.43  (1.355) -5.16  (1.314) -3.49  (1.397)
8.Secondary Outcome
Title Change From Baseline to Week 8 in the Detection Task (DT)
Hide Description The DT is a computerized test that measures simple reaction time and psychomotor speed. The task requires participants to respond by pressing a "yes" button as soon as an onscreen playing card is turned over and is red, and by pressing a "no" button if the card is not red. It takes 2 minutes to be administered. There is no minimum or maximum scores since it is a time-based assessment. Lower score equals better performance. A decrease in score over the course of the study indicates improved speed of processing and psychomotor function. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 182 167
Least Squares Mean (Standard Error)
Unit of Measure: Log10 milliseconds
-0.050  (0.0080) -0.039  (0.0078) -0.033  (0.0082)
9.Secondary Outcome
Title Change From Baseline to Week 8 in the Identification Task (IT)
Hide Description The IT measured choice reaction time: the participant pressed a “yes” button whenever an onscreen playing card turned face up and was red, or a “no” button if the card was not red. The IT took on average 2 minutes to complete. Lower scores equal better performance. A decrease in score over the course of the study indicates improved visual attention/vigilance. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 182 167
Least Squares Mean (Standard Error)
Unit of Measure: Log10 milliseconds
-0.037  (0.0060) -0.030  (0.0059) -0.024  (0.0062)
10.Secondary Outcome
Title Change From Baseline to Week 8 in the One-Back Task
Hide Description The One-Back test measures the cognitive domain of attention and working memory through yes or no responses to 30 trials. The task requires participants to report when a stimulus item presented serially is the same as an item one step back from the item at hand for a total correct responses 0 to 100. It usually takes 2-3 minutes to be administered. Higher scores equal better performance. An increase in score over the course of the study indicates improved attention/working memory. An ANCOVA model was used with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 182 167
Least Squares Mean (Standard Error)
Unit of Measure: Log 10 milliseconds
-0.028  (0.0062) -0.024  (0.0060) -0.022  (0.0063)
11.Secondary Outcome
Title Proportion of Cognitive Dysfunction Improvement Due to Improvement of Depression
Hide Description Improvement of Cognitive Dysfunction is determined using the change from Baseline to Week 8 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score and the Digital Symbol Substitution Test (DSST) total number of correct symbols. The MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression). The DSST assesses relative contributions of speed, memory, executive function and visual scanning. The proportion of direct effect from treatment = DSST difference / (DSST difference + coefficient*MADRS difference).
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Overall Number of Participants Analyzed 175 187
Measure Type: Number
Unit of Measure: proportion of direct effect
75.66 48.69
12.Secondary Outcome
Title Change From Baseline to Week 8 in the MADRS Total Score
Hide Description MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.
Time Frame Baseline, Week 1, Week 4 and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy. Last Observation Carried Forward.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 187 167
Mean (Standard Deviation)
Unit of Measure: score on a scale
Change at Week 1 -3.7  (4.80) -4.6  (5.29) -3.4  (5.03)
Change at Week 4 -9.8  (6.85) -11.6  (7.94) -8.0  (7.98)
Change at Week 8 -14.3  (8.97) -15.5  (9.23) -12.3  (9.64)
13.Secondary Outcome
Title Percentage of Participants With MADRS Response at Week 8
Hide Description MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. MADRS Response was defined as a ≥50% decrease in MADRS Total Score from Baseline.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy. Last Observation Carried Forward.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 187 167
Measure Type: Number
Unit of Measure: percentage of participants
50.9 54.5 41.3
14.Secondary Outcome
Title Percentage of Participants in MADRS Remission at Week 8
Hide Description MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. MADRS Remission was defined as a MADRS total score ≤10.
Time Frame Week 8
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Hide Analysis Population Description
Full Analysis Set included all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy. Last Observation Carried Forward.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 187 167
Measure Type: Number
Unit of Measure: percentage of participants
30.3 33.7 21.6
15.Secondary Outcome
Title Change From Baseline to Week 8 in the Clinical Global Impressions-Severity (CGI-S) Score
Hide Description The CGI-S assesses the clinician's impression of the subject's current state of mental illness and consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill). A MMRM model with baseline*week, center, week, treatment and week*treatment as factors was used for analyses.
Time Frame Baseline, Week 1, Week 4 and Week 8
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Hide Analysis Population Description
Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug and had at least 1 valid post-baseline value for assessment of primary efficacy,with data available for analysis. Repeated Measures Analysis.
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description:
Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.
Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period.
Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
Overall Number of Participants Analyzed 175 187 167
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change from Baseline at Week 1 (n=174, 187,167) -0.289  (0.0426) -0.353  (0.0410) -0.243  (0.0435)
Change from Baseline at Week 4 (n=173,184,165) -0.951  (0.0678) -1.170  (0.0656) -0.617  (0.0693)
Change from Baseline at Week 8 (n=169,179,161) -1.546  (0.0886) -1.698  (0.0859) -1.225  (0.0906)
Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Up to 12 Weeks)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Vortioxetine (Lu AA21004) Duloxetine Placebo
Hide Arm/Group Description Vortioxetine (Lu AA21004) 10 mg, capsules, orally, once daily for one week; then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. Duloxetine 60 mg, capsules, orally, for up to 8 weeks. Duloxetine 30 mg, capsule, orally, once daily for 1 week taper-down period. Placebo matching capsules, orally, once daily for up to 9 weeks (includes 1 week taper down period).
All-Cause Mortality
Vortioxetine (Lu AA21004) Duloxetine Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vortioxetine (Lu AA21004) Duloxetine Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/196 (0.51%)   1/207 (0.48%)   2/191 (1.05%) 
Cardiac disorders       
Acute myocardial infarction  1  0/196 (0.00%)  0/207 (0.00%)  1/191 (0.52%) 
Injury, poisoning and procedural complications       
Craniocerebral injury  1  0/196 (0.00%)  1/207 (0.48%)  0/191 (0.00%) 
Subdural haematoma  1  0/196 (0.00%)  1/207 (0.48%)  0/191 (0.00%) 
Psychiatric disorders       
Depression  1  0/196 (0.00%)  0/207 (0.00%)  1/191 (0.52%) 
Suicide attempt  1  1/196 (0.51%)  0/207 (0.00%)  0/191 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vortioxetine (Lu AA21004) Duloxetine Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   73/196 (37.24%)   84/207 (40.58%)   41/191 (21.47%) 
Gastrointestinal disorders       
Nausea  1  40/196 (20.41%)  43/207 (20.77%)  8/191 (4.19%) 
Diarrhoea  1  11/196 (5.61%)  6/207 (2.90%)  5/191 (2.62%) 
Dry mouth  1  6/196 (3.06%)  16/207 (7.73%)  9/191 (4.71%) 
Infections and infestations       
Nasopharyngitis  1  7/196 (3.57%)  8/207 (3.86%)  11/191 (5.76%) 
Metabolism and nutrition disorders       
Decreased appetite  1  3/196 (1.53%)  12/207 (5.80%)  1/191 (0.52%) 
Nervous system disorders       
Headache  1  20/196 (10.20%)  24/207 (11.59%)  16/191 (8.38%) 
Dizziness  1  6/196 (3.06%)  11/207 (5.31%)  5/191 (2.62%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
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
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01564862     History of Changes
Other Study ID Numbers: LuAA21004_202
2011-005298-22 ( EudraCT Number )
U1111-1126-0091 ( Registry Identifier: WHO )
First Submitted: March 26, 2012
First Posted: March 28, 2012
Results First Submitted: January 13, 2015
Results First Posted: February 5, 2015
Last Update Posted: February 5, 2015