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Efficacy and Safety of Vortioxetine (Lu AA21004) in the Treatment of Patients With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT00672620
Recruitment Status : Completed
First Posted : May 6, 2008
Results First Posted : December 18, 2013
Last Update Posted : December 18, 2013
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Vortioxetine
Drug: Duloxetine
Drug: Placebo
Enrollment 611
Recruitment Details Participants took part in the study at 47 investigative sites in the United States from 10 April 2008 to 30 December 2008.
Pre-assignment Details Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 4 treatment groups, once a day placebo, 2.5 mg, 5 mg vortioxetine, or 60 mg duloxetine.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description Placebo-matching capsules, orally, once daily for up to 9 weeks. Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period. Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period. Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period
Period Title: Overall Study
Started 153 153 153 152
Treated 151 149 153 150
Completed 120 99 122 110
Not Completed 33 54 31 42
Reason Not Completed
Adverse Event             7             7             12             17
Lack of Efficacy             1             2             2             0
Noncompliance with Study Drug             3             4             0             2
Protocol Deviations             5             7             2             5
Withdrawal of Consent             6             12             5             6
Lost to Follow-up             8             19             8             11
Reason not Specified             3             3             2             1
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg Total
Hide Arm/Group Description Placebo-matching capsules, orally, once daily for up to 9 weeks. Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period. Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period. Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period. Total of all reporting groups
Overall Number of Baseline Participants 153 153 153 152 611
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
42.6  (13.76) 42.6  (12.85) 43.1  (13.89) 42.7  (14.38) 42.7  (13.70)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
≤55 years 122 127 125 123 497
>55 years 31 26 28 29 114
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
Female
93
  60.8%
98
  64.1%
106
  69.3%
91
  59.9%
388
  63.5%
Male
60
  39.2%
55
  35.9%
47
  30.7%
61
  40.1%
223
  36.5%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
Caucasian (White, including Hispanic) 121 112 108 111 452
Black 28 35 40 36 139
Asian 3 3 3 3 12
American Indian or Alaska Native 1 2 0 0 3
Native Hawaiian/ Other Pacific Islander 0 1 0 1 2
[1]
Measure Description: Number of participants for whom Race data were available were 153, 153, 151 and 151 respectively.
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
Hispanic/Latino 35 21 19 28 103
Non-Hispanic/Non-Latino 118 132 133 123 506
[1]
Measure Description: Number of participants for whom Ethnicity data were available were 153, 153, 152 and 151 respectively.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
153 153 153 152 611
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
84.22  (20.144) 85.08  (24.126) 88.61  (25.779) 87.44  (20.695) 86.34  (22.823)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
168.98  (9.141) 169.50  (9.385) 167.98  (9.833) 170.37  (9.624) 169.21  (9.515)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
29.58  (7.263) 29.48  (7.479) 31.38  (8.846) 30.14  (6.773) 30.15  (7.649)
Smoking Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
Never smoked 72 81 87 75 315
Current smoker 47 42 45 36 170
Ex-smoker 34 30 21 41 126
Alcohol consumption  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
Never 50 49 48 49 196
Once monthly or less often 56 49 62 51 218
Once per week 23 26 23 21 93
2-to-6 times/week 22 20 17 28 87
Daily 2 9 3 3 17
24-item Hamilton Depression Scale total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
29.5  (6.05) 29.8  (5.42) 29.8  (5.58) 28.7  (5.08) 29.5  (5.55)
[1]
Measure Description: The 24-item Hamilton Depression Scale (HAM-D24) is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74, where a higher score indicates a greater depressive state.
Montgomery Åsberg Depression Rating Scale (MADRS) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
30.0  (4.39) 29.8  (4.61) 30.1  (4.51) 29.4  (4.31) 29.8  (4.45)
[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 153 participants 153 participants 153 participants 152 participants 611 participants
18.8  (5.53) 19.3  (5.22) 18.7  (5.74) 17.4  (5.47) 18.5  (5.53)
[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 to 56, where <17 indicates mild severity, 18–24 mild to moderate severity and 25–30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety.
Clinical Global Impression - Severity scale score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 153 participants 153 participants 153 participants 152 participants 611 participants
4.5  (0.62) 4.6  (0.62) 4.6  (0.65) 4.5  (0.67) 4.5  (0.64)
[1]
Measure Description: The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
1.Primary Outcome
Title Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8
Hide Description The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. Least squares (LS) means were from an Analysis of Covariance (ANCOVA) model with terms for treatment and center as factors and the Baseline rank value as a covariate.
Time Frame Baseline and Week 8
Hide 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. Last observation carried forward (LOCF) was used.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-10.50  (0.757) -12.04  (0.744) -11.08  (0.737) -13.47  (0.750)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 5 mg
Comments All statistical tests were 2-sided with 95% confidence intervals (CIs), and with P-values evaluated at the 5% significance level (ie, statistical significance if P<0.05). To control for multiplicity, a pre-specified sequential testing procedure was applied to compare 5 mg and 2.5 mg vortioxetine to placebo; as soon as an endpoint was non-significant at 0.05, the testing procedure stopped for all subsequent endpoints.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.577
Comments Pre-specified sequential statistical testing procedure indicates that when p-value >0.05, hierarchical testing stops and for subsequent endpoints in the sequence a nominal p-value is provided.
Method ANCOVA
Comments ANCOVA with treatment and center as fixed factors, baseline HAM-D24 as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-2.61 to 1.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.036
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine 2.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.138
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with treatment and center as fixed factors, baseline HAM-D24 as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.54
Confidence Interval (2-Sided) 95%
-3.58 to 0.50
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.038
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Duloxetine 60 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with treatment and center as fixed factors, baseline HAM-D24 as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.96
Confidence Interval (2-Sided) 95%
-5.02 to -0.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.047
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed
Hide Description The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. LS means were from an ANCOVA model with terms for treatment and center as factors and the Baseline rank value as a covariate.
Time Frame Baseline and Weeks 1, 2, 4, and 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=142, 143, 150, 147) -5.12  (0.515) -5.44  (0.497) -5.28  (0.491) -5.66  (0.500)
Week 2 (n=149, 146, 153, 149) -7.19  (0.567) -7.95  (0.557) -7.99  (0.552) -8.42  (0.562)
Week 4 (n=149, 146, 153, 149) -9.39  (0.663) -9.94  (0.651) -8.96  (0.645) -10.88  (0.657)
Week 6 (n=149, 146, 153, 149) -10.43  (0.706) -11.21  (0.694) -10.97  (0.687) -12.78  (0.700)
3.Secondary Outcome
Title Percentage of Responders in HAM-D 24 Total Score by Study Visit
Hide Description A responder is defined as a participant with a ≥50% decrease from Baseline in HAM-D24 total score. The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74, where a higher score indicates a greater depressive state.
Time Frame Baseline and Weeks 1, 2, 4, 6 and 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Measure Type: Number
Unit of Measure: percentage of participants
Week 1 (n=142, 143, 150, 147) 9.2 8.4 8.7 10.2
Week 2 (n=149, 146, 153, 149) 15.4 17.1 17.6 22.1
Week 4 (n=149, 146, 153, 149) 26.2 30.8 24.2 34.9
Week 6 (n=149, 146, 153, 149) 32.9 37.7 37.3 47.0
Week 8 (n=149, 146, 153, 149) 32.2 41.1 37.9 51.0
4.Secondary Outcome
Title Percentage of Participants With a Sustained Response in HAM-D24
Hide Description A sustained response is defined as a ≥ 20% decrease from Baseline in HAM-D24 total score obtained at Week 1 and sustained through Week 7 and at least 50% decrease from Baseline at Week 8.
Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with available data.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Measure Type: Number
Unit of Measure: percentage of participants
12.1 15.8 17.0 21.5
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
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; LOCF was used.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Measure Type: Number
Unit of Measure: percentage of participants
22.8 28.8 23.5 37.6
6.Secondary Outcome
Title Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
Time Frame Baseline and Weeks 1, 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=142, 143, 150, 147) -4.90  (0.530) -5.16  (0.511) -5.06  (0.505) -5.49  (0.514)
Week 2 (n=149, 146, 153, 149) -7.57  (0.615) -7.71  (0.605) -7.81  (0.599) -8.95  (0.609)
Week 4 (n=149, 146, 153, 149) -9.66  (0.693) -9.58  (0.681) -9.35  (0.675) -11.34  (0.686)
Week 6 (n=149, 146, 153, 149) -11.04  (0.770) -11.25  (0.757) -11.27  (0.750) -13.29  (0.763)
Week 8 (149, 146, 153, 149) -11.22  (0.819) -11.61  (0.805) -11.30  (0.797) -14.10  (0.811)
7.Secondary Outcome
Title Clinical Global Impression Scale-Global Improvement Scale
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 an ANCOVA model with treatment and center as fixed factors and the CGI-S Baseline value as a covariate.
Time Frame Baseline and Weeks 1, 2, 4, 6 and 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=142, 143, 149, 147) 3.54  (0.067) 3.42  (0.065) 3.46  (0.064) 3.31  (0.065)
Week 2 (n=149, 146, 153, 149) 3.21  (0.077) 3.17  (0.076) 3.10  (0.075) 2.99  (0.076)
Week 4 (149, 146, 153, 149) 2.97  (0.085) 2.93  (0.084) 2.87  (0.083) 2.73  (0.084)
Week 6 (149, 146, 153, 149) 2.83  (0.091) 2.82  (0.090) 2.74  (0.089) 2.50  (0.090)
Week 8 (n=149, 146, 153, 149) 2.79  (0.098) 2.73  (0.096) 2.63  (0.095) 2.39  (0.097)
8.Secondary Outcome
Title Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S)
Hide Description The MADRS-S is a patient-reported outcome measure based on MADRS, administered to evaluate treatment effectiveness in depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored between 0 (best) and 3 (worst). The total score is calculated by summing the answers of the nine items, ranging between 0 and 27 (higher scores indicate increased impairment). LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Weeks 1, 4 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with available data at Baseline; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 148 145 152 149
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=141, 142, 149, 146) -2.51  (0.310) -2.43  (0.299) -2.74  (0.295) -2.88  (0.299)
Week 4 (148, 145, 152, 149) -4.02  (0.348) -3.65  (0.342) -3.69  (0.338) -4.89  (0.342)
Week 8 (n=148, 145, 152, 149) -4.25  (0.370) -3.98  (0.364) -4.04  (0.360) -5.70  (0.364)
9.Secondary Outcome
Title Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
Time Frame Baseline and Weeks 1, 2, 4, 6 and 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=142, 143, 150, 147) -2.63  (0.356) -2.98  (0.343) -2.55  (0.339) -2.30  (0.346)
Week 2 (n=149, 146, 153, 149) -3.82  (0.419) -4.41  (0.412) -3.76  (0.408) -3.94  (0.415)
Week 4 (n=149, 146, 153, 149) -5.12  (0.457) -5.10  (0.450) -4.25  (0.445) -4.88  (0.454)
Week 6 (n=149, 146, 153, 149) -5.84  (0.482) -5.77  (0.474) -4.89  (0.469) -6.15  (0.478)
Week 8 (n=149, 146, 153, 149) -5.75  (0.502) -5.91  (0.494) -5.29  (0.488) -6.56  (0.498)
10.Secondary Outcome
Title Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale
Hide Description The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate 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. Considering total clinical experience, a patient is assessed on severity of mental illness 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. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Weeks 1, 2, 4, 6 and 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=142, 143, 150, 147) -0.28  (0.055) -0.40  (0.053) -0.37  (0.053) -0.44  (0.054)
Week 2 (n=149, 146, 153, 149) -0.63  (0.071) -0.65  (0.069) -0.66  (0.069) -0.75  (0.070)
Week 4 (n=149, 146, 153, 149) -0.92  (0.086) -0.92  (0.085) -0.90  (0.084) -1.12  (0.085)
Week 6 (n=149, 146, 153, 149) -1.11  (0.094) -1.08  (0.092) -1.08  (0.091) -1.39  (0.093)
Week 8 (n=149, 146, 153, 149) -1.14  (0.103) -1.21  (0.102) -1.17  (0.101) -1.56  (0.102)
11.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 an ANCOVA model 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 with available data at Baseline; LOCF was used.
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 130 122 123 114
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-6.83  (0.638) -6.46  (0.640) -6.59  (0.641) -8.91  (0.672)
12.Secondary Outcome
Title Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire
Hide Description Healthcare resource utilization was assessed by the Health Economic Assessment (HEA) questionnaire, which monitors participants absenteeism from work, as well as resource use such as visits to a general practitioner, outpatient and inpatient services, hospitalization, medications, and other relevant services over the past 8 weeks.
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description:
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
Overall Number of Participants Analyzed 149 146 153 149
Measure Type: Number
Unit of Measure: participants
Baseline: Any resource use 40 51 42 42
Baseline: Any hospitalization-related services 4 1 0 3
Baseline: Hospitalization related to depression 2 1 0 0
Baseline: Any sick leave 18 11 11 14
Baseline: Sick leave related to depression 13 9 10 11
Week 8: Any resource use 21 19 20 27
Week 8: Any hospitalization-related service 1 0 1 2
Week 8: Hospitalization related to depression 0 0 0 1
Week 8: Any sick leave 5 5 9 5
Week 8: Sick leave related to depression 2 4 3 2
Time Frame Adverse events were collected during the 8-week treatment period and a 4-week follow-up period.
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 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Hide Arm/Group Description Placebo-matching capsules, orally, once daily for up to 9 weeks. Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period. Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period. Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period.
All-Cause Mortality
Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/151 (1.32%)   0/149 (0.00%)   3/153 (1.96%)   2/150 (1.33%) 
Cardiac disorders         
Acute myocardial infarction  1  0/151 (0.00%)  0/149 (0.00%)  0/153 (0.00%)  1/150 (0.67%) 
Atrial fibrillation  1  0/151 (0.00%)  0/149 (0.00%)  1/153 (0.65%)  0/150 (0.00%) 
Coronary artery disease  1  0/151 (0.00%)  0/149 (0.00%)  1/153 (0.65%)  0/150 (0.00%) 
Injury, poisoning and procedural complications         
Head injury  1  0/151 (0.00%)  0/149 (0.00%)  1/153 (0.65%)  0/150 (0.00%) 
Nervous system disorders         
Convulsion  1  0/151 (0.00%)  0/149 (0.00%)  1/153 (0.65%)  0/150 (0.00%) 
Psychiatric disorders         
Depression  1  1/151 (0.66%)  0/149 (0.00%)  0/153 (0.00%)  0/150 (0.00%) 
Panic attack  1  0/151 (0.00%)  0/149 (0.00%)  0/153 (0.00%)  1/150 (0.67%) 
Surgical and medical procedures         
Abortion induced  1  1/151 (0.66%)  0/149 (0.00%)  0/153 (0.00%)  0/150 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Vortioxetine 2.5 mg Vortioxetine 5 mg Duloxetine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   81/151 (53.64%)   83/149 (55.70%)   87/153 (56.86%)   120/150 (80.00%) 
Eye disorders         
Vision blurred  1  3/151 (1.99%)  1/149 (0.67%)  1/153 (0.65%)  4/150 (2.67%) 
Gastrointestinal disorders         
Nausea  1  16/151 (10.60%)  24/149 (16.11%)  44/153 (28.76%)  63/150 (42.00%) 
Dry mouth  1  11/151 (7.28%)  16/149 (10.74%)  16/153 (10.46%)  40/150 (26.67%) 
Diarrhoea  1  13/151 (8.61%)  7/149 (4.70%)  14/153 (9.15%)  19/150 (12.67%) 
Constipation  1  11/151 (7.28%)  6/149 (4.03%)  6/153 (3.92%)  18/150 (12.00%) 
Vomiting  1  1/151 (0.66%)  1/149 (0.67%)  7/153 (4.58%)  5/150 (3.33%) 
Dyspepsia  1  3/151 (1.99%)  6/149 (4.03%)  3/153 (1.96%)  2/150 (1.33%) 
Abdominal pain upper  1  2/151 (1.32%)  1/149 (0.67%)  6/153 (3.92%)  2/150 (1.33%) 
Abdominal pain  1  2/151 (1.32%)  1/149 (0.67%)  0/153 (0.00%)  5/150 (3.33%) 
Stomach discomfort  1  4/151 (2.65%)  3/149 (2.01%)  4/153 (2.61%)  1/150 (0.67%) 
Flatulence  1  2/151 (1.32%)  3/149 (2.01%)  3/153 (1.96%)  1/150 (0.67%) 
General disorders         
Fatigue  1  5/151 (3.31%)  3/149 (2.01%)  3/153 (1.96%)  13/150 (8.67%) 
Feeling jittery  1  0/151 (0.00%)  0/149 (0.00%)  2/153 (1.31%)  4/150 (2.67%) 
Irritability  1  4/151 (2.65%)  2/149 (1.34%)  0/153 (0.00%)  1/150 (0.67%) 
Infections and infestations         
Viral upper respiratory tract infection  1  3/151 (1.99%)  2/149 (1.34%)  2/153 (1.31%)  6/150 (4.00%) 
Injury, poisoning and procedural complications         
Accidental overdose  1  1/151 (0.66%)  6/149 (4.03%)  1/153 (0.65%)  2/150 (1.33%) 
Investigations         
Weight decreased  1  1/151 (0.66%)  0/149 (0.00%)  0/153 (0.00%)  4/150 (2.67%) 
Blood pressure increased  1  1/151 (0.66%)  1/149 (0.67%)  1/153 (0.65%)  3/150 (2.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  1/151 (0.66%)  1/149 (0.67%)  2/153 (1.31%)  8/150 (5.33%) 
Anorexia  1  0/151 (0.00%)  1/149 (0.67%)  3/153 (1.96%)  5/150 (3.33%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  5/151 (3.31%)  2/149 (1.34%)  1/153 (0.65%)  3/150 (2.00%) 
Nervous system disorders         
Headache  1  18/151 (11.92%)  20/149 (13.42%)  24/153 (15.69%)  21/150 (14.00%) 
Dizziness  1  7/151 (4.64%)  10/149 (6.71%)  9/153 (5.88%)  22/150 (14.67%) 
Somnolence  1  6/151 (3.97%)  3/149 (2.01%)  9/153 (5.88%)  20/150 (13.33%) 
Sedation  1  4/151 (2.65%)  3/149 (2.01%)  5/153 (3.27%)  1/150 (0.67%) 
Tension headache  1  0/151 (0.00%)  0/149 (0.00%)  3/153 (1.96%)  4/150 (2.67%) 
Tremor  1  1/151 (0.66%)  1/149 (0.67%)  3/153 (1.96%)  4/150 (2.67%) 
Psychiatric disorders         
Insomnia  1  6/151 (3.97%)  6/149 (4.03%)  6/153 (3.92%)  11/150 (7.33%) 
Restlessness  1  1/151 (0.66%)  2/149 (1.34%)  3/153 (1.96%)  5/150 (3.33%) 
Anxiety  1  2/151 (1.32%)  1/149 (0.67%)  5/153 (3.27%)  1/150 (0.67%) 
Libido decreased  1  3/151 (1.99%)  3/149 (2.01%)  3/153 (1.96%)  4/150 (2.67%) 
Orgasm abnormal  1  0/151 (0.00%)  0/149 (0.00%)  3/153 (1.96%)  3/150 (2.00%) 
Respiratory, thoracic and mediastinal disorders         
Yawning  1  0/151 (0.00%)  0/149 (0.00%)  1/153 (0.65%)  3/150 (2.00%) 
Skin and subcutaneous tissue disorders         
Hyperhidrosis  1  4/151 (2.65%)  4/149 (2.68%)  4/153 (2.61%)  11/150 (7.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
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: NCT00672620     History of Changes
Other Study ID Numbers: LuAA21004_304
U1111-1114-3497 ( Registry Identifier: WHO )
First Submitted: May 2, 2008
First Posted: May 6, 2008
Results First Submitted: October 25, 2013
Results First Posted: December 18, 2013
Last Update Posted: December 18, 2013