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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00672958
Recruitment Status : Completed
First Posted : May 6, 2008
Results First Posted : December 13, 2013
Last Update Posted : December 13, 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: Placebo
Enrollment 600
Recruitment Details Participants took part in the study at 47 investigative sites in the United States from 07 April 2008 to 12 November 2008.
Pre-assignment Details Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 2 treatment groups, once a day placebo or 5 mg vortioxetine.
Arm/Group Title Placebo Vortioxetine
Hide Arm/Group Description Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks. Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Period Title: Overall Study
Started 300 300
Safety Set 298 [1] 299 [1]
Full Analysis Set 286 [2] 292 [2]
Completed 236 244
Not Completed 64 56
Reason Not Completed
Adverse Event             11             9
Lack of Efficacy             6             11
Non-compliance with study drug             2             3
Protocol deviations             11             5
Voluntary withdrawal             12             8
Lost to Follow-up             22             17
Reason not specified             0             3
[1]
All randomized patients who received at least 1 dose of double-blind study drug.
[2]
All safety set patients who had at least 1 valid postbaseline primary efficacy assessment.
Arm/Group Title Placebo Vortioxetine Total
Hide Arm/Group Description Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks. Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks. Total of all reporting groups
Overall Number of Baseline Participants 300 300 600
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 300 participants 300 participants 600 participants
42.4  (12.70) 42.5  (13.04) 42.4  (12.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 300 participants 300 participants 600 participants
Female
164
  54.7%
186
  62.0%
350
  58.3%
Male
136
  45.3%
114
  38.0%
250
  41.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 300 participants 300 participants 600 participants
Caucasian (White, including Hispanic) 216 209 425
Black 78 81 159
Asian 4 8 12
American Indian or Alaska Native 2 1 3
Native Hawaiian/ Other Pacific Islander 0 1 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 300 participants 300 participants 600 participants
Hispanic/Latino 36 34 70
Non-Hispanic/Non-Latino 264 266 530
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 300 participants 300 participants 600 participants
300 300 600
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 300 participants 300 participants 600 participants
89.53  (23.326) 86.63  (23.528) 88.08  (23.453)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 300 participants 300 participants 600 participants
170.36  (9.815) 168.67  (9.815) 169.51  (9.843)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 300 participants 300 participants 600 participants
30.84  (7.675) 30.48  (8.217) 30.66  (7.946)
Waist circumference  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 300 participants 300 participants 600 participants
97.58  (17.757) 96.22  (18.961) 96.90  (18.366)
Smoking classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 300 participants 300 participants 600 participants
Never smoked 119 123 242
Current smoker 124 116 240
Ex-smoker 57 61 118
Alcohol consumption  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 300 participants 300 participants 600 participants
Never 108 106 214
Once monthly or less often 102 124 226
Once per week 46 41 87
2-to-6 times/week 33 21 54
Daily 11 8 19
24-item Hamilton Depression Scale total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 300 participants 300 participants 600 participants
32.2  (5.50) 32.7  (5.42) 32.5  (5.46)
[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 300 participants 300 participants 600 participants
34.0  (3.41) 34.1  (3.39) 34.1  (3.40)
[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 300 participants 300 participants 600 participants
19.5  (6.19) 19.3  (5.24) 19.4  (5.73)
[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 300 participants 300 participants 600 participants
4.8  (0.66) 4.8  (0.68) 4.8  (0.67)
[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 6
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 range is 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 treatment and center as fixed factors and the baseline value as a covariate.
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, which includes all randomized participants who received at least 1 dose of study drug and had at least 1 postbaseline value for assessment of primary efficacy. Last observation carried forward (LOCF) was used.
Arm/Group Title Placebo Vortioxetine
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-13.87  (0.662) -14.61  (0.650)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine
Comments Change from Baseline in HAM-D24 total score at Week 6 was tested at significance level 0.05. To control for multiplicity, subsequent endpoints were to be tested in a sequential testing procedure at significance level 0.025; as soon as an endpoint in a sequence was non-significant at 0.025, the testing procedure was stopped for all subsequent endpoints in that sequence.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.407
Comments Pre-specified sequential statistical testing procedure indicates that when p-value for change from baseline in HAMD-24 at Week 6 >0.05, hierarchical testing stops and for subsequent endpoints in the sequence a nominal p-value is provided.
Method ANCOVA
Comments Analysis of covariance (ANCOVA), with treatment and center as fixed factors and baseline HAM-D24 as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-2.48 to 1.01
Estimation Comments [Not Specified]
2.Primary 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 treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame Baseline and Weeks 1, 2, 3, 4 and 5
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
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=281, 286) -6.03  (0.394) -5.96  (0.387)
Week 2 (n= 286, 291) -9.30  (0.505) -9.05  (0.496)
Week 3 (n= 286, 292) -11.05  (0.545) -11.73  (0.536)
Week 4 (n= 286, 292) -12.33  (0.579) -12.66  (0.568)
Week 5 (n=286, 292) -13.11  (0.628) -13.98  (0.617)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine
Comments Comparison of change from Baseline at Week 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.901
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.97 to 1.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine
Comments Change from Baseline at Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.701
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
-1.07 to 1.59
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine
Comments Change from Baseline at Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.356
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.68
Confidence Interval (2-Sided) 95%
-2.11 to 0.76
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.670
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-1.85 to 1.19
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Vortioxetine
Comments Change from Baseline at Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.304
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.87
Confidence Interval (2-Sided) 95%
-2.52 to 0.79
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Responders in HAM-D24 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, 3, 4, 5 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
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Measure Type: Number
Unit of Measure: percentage of participants
Week 1 (n=281, 286) 7.8 7.0
Week 2 (n=286, 291) 23.8 21.0
Week 3 (n=286, 292) 31.8 32.9
Week 4 (n=286, 292) 39.2 37.0
Week 5 (n=286, 292) 44.4 43.8
Week 6 (n=286, 292) 46.2 46.2
4.Secondary Outcome
Title Percentage of Participants in MADRS Remission at Week 6
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 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; LOCF was used.
Arm/Group Title Placebo Vortioxetine
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Measure Type: Number
Unit of Measure: percentage of participants
32.2 29.1
5.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 5 and at least 50% decrease from Baseline at Week 6.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Participants with missing values were classified as nonsustained responders/remitters.
Arm/Group Title Placebo Vortioxetine
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Measure Type: Number
Unit of Measure: percentage of participants
21.0 19.5
6.Secondary Outcome
Title Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
Time Frame Baseline and Weeks 1, 2, 3, 4, 5 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
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=281, 286) -6.88  (0.418) -6.38  (0.412)
Week 2 (n=286, 291) -10.57  (0.530) -9.82  (0.523)
Week 3 (n=286, 292) -12.48  (0.583) -12.76  (0.575)
Week 4 (n=286, 292) -13.72  (0.624) -13.70  (0.615)
Week 5 (n=286, 292) -14.40  (0.673) -15.12  (0.664)
Week 6 (n=286, 292) -15.48  (0.708) -15.80  (0.698)
7.Secondary Outcome
Title Change From Baseline in Hamilton Anxiety Scale (HAM-A)
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
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=281, 286) -3.25  (0.288) -3.21  (0.284)
Week 2 (n=286, 291) -4.92  (0.343) -4.77  (0.338)
Week 4 (n=286, 292) -6.52  (0.393) -6.88  (0.387)
Week 6 (n=286, 292) -7.60  (0.419) -7.84  (0.413)
8.Secondary Outcome
Title Change From Baseline in Clinical Global Impression Scale-Severity of Illness
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, 3, 4, 5 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
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=281, 286) -0.47  (0.045) -0.40  (0.044)
Week 2 (n=286, 291) -0.82  (0.061) -0.82  (0.060)
Week 3 (n=286, 292) -1.07  (0.069) -1.08  (0.067)
Week 4 (n=286, 292) -1.25  (0.073) -1.20  (0.072)
Week 5 (n=286, 292) -1.28  (0.079) -1.36  (0.077)
Week 6 (n=286, 292) -1.46  (0.085) -1.46  (0.083)
9.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, 3, 4, 5 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
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=281, 286) 3.38  (0.048) 3.46  (0.047)
Week 2 (n=286, 291) 3.09  (0.062) 3.08  (0.061)
Week 3 (n=286, 292) 2.90  (0.066) 2.84  (0.065)
Week 4 (n=286, 292) 2.74  (0.070) 2.75  (0.069)
Week 5 (n=286, 292) 2.74  (0.073) 2.65  (0.071)
Week 6 (n=286, 292) 2.61  (0.076) 2.57  (0.075)
10.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 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
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Week 1 (n=279, 286) -2.81  (0.214) -2.73  (0.210)
Week 4 (n=284, 292) -4.18  (0.272) -4.05  (0.267)
Week 6 (n=284, 292) -4.56  (0.313) -4.97  (0.307)
11.Secondary Outcome
Title Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6
Hide Description The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are: 1. Limitation in physical activities because of health problems. 2. Limitations in usual role activities because of physical health problems. 3. Bodily pain. 4. Limitations in social activities because of physical or emotional problems. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perception. Each scale ranges from 0 (best) - 100 (worst). 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 Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where Baseline SF-36 data were available; LOCF was used.
Arm/Group Title Placebo Vortioxetine
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 279 287
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Physical functioning 5.47  (1.277) 6.87  (1.264)
Role - physical 11.73  (1.569) 14.41  (1.549)
Bodily pain 10.77  (1.460) 10.39  (1.445)
General health 7.65  (0.985) 7.37  (0.975)
Vitality 18.00  (1.455) 17.34  (1.440)
Social functioning 21.34  (1.687) 22.01  (1.667)
Role - emotional 19.43  (1.756) 20.76  (1.732)
Mental health 18.98  (1.401) 20.00  (1.385)
12.Secondary Outcome
Title Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 6
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 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set where data were available; LOCF was used.
Arm/Group Title Placebo Vortioxetine
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 217 220
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-6.61  (0.548) -6.69  (0.557)
13.Secondary Outcome
Title Health Care 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 the 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 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Placebo Vortioxetine
Hide Arm/Group Description:
Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Number of Participants Analyzed 286 292
Measure Type: Number
Unit of Measure: participants
Baseline: Any resource use 82 77
Baseline: Any hospitalization-related services 1 0
Baseline: Hospitalization related to depression 1 0
Baseline: Any sick leave 16 21
Baseline: Sick leave related to depression 9 13
Week 6: Any resource use 58 41
Week 6: Any hospitalization-related service 3 1
Week 6: Hospitalization related to depression 0 0
Week 6: Any sick leave 7 7
Week 6: Sick leave related to depression 3 2
Time Frame Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug.
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
Hide Arm/Group Description Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks. Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
All-Cause Mortality
Placebo Vortioxetine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Vortioxetine
Affected / at Risk (%) Affected / at Risk (%)
Total   4/298 (1.34%)   7/299 (2.34%) 
Immune system disorders     
Drug hypersensitivity  1  0/298 (0.00%)  1/299 (0.33%) 
Infections and infestations     
Herpes zoster  1  0/298 (0.00%)  1/299 (0.33%) 
Puncture site infection  1  1/298 (0.34%)  0/299 (0.00%) 
Injury, poisoning and procedural complications     
Injury  1  0/298 (0.00%)  1/299 (0.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer  1  0/298 (0.00%)  1/299 (0.33%) 
Laryngeal cancer  1  1/298 (0.34%)  0/299 (0.00%) 
Renal cell carcinoma  1  0/298 (0.00%)  1/299 (0.33%) 
Nervous system disorders     
Cerebrovascular accident  1  0/298 (0.00%)  1/299 (0.33%) 
Convulsion  1  0/298 (0.00%)  1/299 (0.33%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  1/298 (0.34%)  0/299 (0.00%) 
Ectopic pregnancy  1  1/298 (0.34%)  0/299 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Vortioxetine
Affected / at Risk (%) Affected / at Risk (%)
Total   142/298 (47.65%)   168/299 (56.19%) 
Gastrointestinal disorders     
Nausea  1  28/298 (9.40%)  57/299 (19.06%) 
Diarrhoea  1  21/298 (7.05%)  34/299 (11.37%) 
Dry mouth  1  19/298 (6.38%)  25/299 (8.36%) 
Abdominal pain  1  3/298 (1.01%)  12/299 (4.01%) 
Dyspepsia  1  10/298 (3.36%)  5/299 (1.67%) 
Constipation  1  6/298 (2.01%)  9/299 (3.01%) 
Vomiting  1  4/298 (1.34%)  8/299 (2.68%) 
General disorders     
Fatigue  1  7/298 (2.35%)  5/299 (1.67%) 
Irritability  1  7/298 (2.35%)  3/299 (1.00%) 
Infections and infestations     
Nasopharyngitis  1  5/298 (1.68%)  7/299 (2.34%) 
Upper respiratory tract infection  1  6/298 (2.01%)  3/299 (1.00%) 
Urinary tract infection  1  5/298 (1.68%)  6/299 (2.01%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  3/298 (1.01%)  8/299 (2.68%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  5/298 (1.68%)  7/299 (2.34%) 
Nervous system disorders     
Headache  1  45/298 (15.10%)  51/299 (17.06%) 
Dizziness  1  22/298 (7.38%)  19/299 (6.35%) 
Somnolence  1  10/298 (3.36%)  11/299 (3.68%) 
Psychiatric disorders     
Insomnia  1  9/298 (3.02%)  6/299 (2.01%) 
Depression  1  5/298 (1.68%)  7/299 (2.34%) 
Initial insomnia  1  4/298 (1.34%)  6/299 (2.01%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  7/298 (2.35%)  4/299 (1.34%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 11.1
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: NCT00672958     History of Changes
Other Study ID Numbers: LuAA21004_303
U1111-1114-2328 ( Registry Identifier: WHO )
First Submitted: May 2, 2008
First Posted: May 6, 2008
Results First Submitted: April 19, 2013
Results First Posted: December 13, 2013
Last Update Posted: December 13, 2013