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Investigating the Effect of Vortioxetine in Adult ADHD Patients

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ClinicalTrials.gov Identifier: NCT02327013
Recruitment Status : Completed
First Posted : December 30, 2014
Results First Posted : January 31, 2018
Last Update Posted : March 7, 2018
Sponsor:
Information provided by (Responsible Party):
H. Lundbeck A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Attention Deficit Hyperactivity Disorder
Interventions Drug: vortioxetine 10 mg tablet
Drug: vortioxetine 20 mg tablet
Other: Placebo tablet
Enrollment 227
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vortioxetine 10mg Vortioxetine 20mg Placebo - Placebo Placebo - Vortioxetine 10mg Placebo - Vortioxetine 20mg
Hide Arm/Group Description Patients randomized to treatment with vortioxetine 10mg/day in Stage 1 and continued on the same treatment in Stage 2. Patients randomized to treatment with vortioxetine 20mg/day in Stage 1 and continued on the same treatment in Stage 2. Patients randomized to treatment with placebo in Stage 1 and continued on the same treatment in Stage 2. This group will consist of placebo responders and placebo non-responders who were re-randomized to Placebo in Stage 2. Patients that did not respond to placebo in Stage 1 and were re-randomized to treatment with vortioxetine 10mg/day in Stage 2. Patients that did not respond to placebo in Stage 1 and were re-randomized to treatment with vortioxetine 20mg/day in Stage 2.
Period Title: Overall Study
Started 49 45 96 21 16
Completed 36 29 54 20 12
Not Completed 13 16 42 1 4
Reason Not Completed
Adverse Event             4             4             3             0             1
Lack of Efficacy             2             0             5             0             1
Non-compliance with IMP             1             2             7             0             0
Withdrawal of Consent             1             0             3             0             0
Lost to Follow-up             2             4             5             0             0
Administrative or other reason(s)             1             5             11             1             1
Protocol Violation             0             0             3             0             1
Withdrawal before treatment             2             1             5             0             0
Arm/Group Title Placebo (Stage 1) Vortioxetine 10mg (Stage 1) Vortioxetine 20mg (Stage 1) Total
Hide Arm/Group Description Patients treated wtih placebo in Stage 1. Patients treated with vortioxetine 10mg in Stage 1. Patients treated with vortioxetine 20mg in Stage 1. Total of all reporting groups
Overall Number of Baseline Participants 128 47 44 219
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 128 participants 47 participants 44 participants 219 participants
37.1  (10.3) 35.8  (9.6) 37.2  (10.4) 36.9  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 128 participants 47 participants 44 participants 219 participants
Female
66
  51.6%
24
  51.1%
19
  43.2%
109
  49.8%
Male
62
  48.4%
23
  48.9%
25
  56.8%
110
  50.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 128 participants 47 participants 44 participants 219 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
8
   6.3%
4
   8.5%
1
   2.3%
13
   5.9%
Native Hawaiian or Other Pacific Islander
2
   1.6%
1
   2.1%
0
   0.0%
3
   1.4%
Black or African American
15
  11.7%
3
   6.4%
8
  18.2%
26
  11.9%
White
97
  75.8%
37
  78.7%
31
  70.5%
165
  75.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
6
   4.7%
2
   4.3%
4
   9.1%
12
   5.5%
1.Primary Outcome
Title Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score
Hide Description AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Stage 1 Vortioxetine 10mg, Stage 1 Vortioxetine 20mg, Stage 1 Placebo, Stage 2 Vortioxetine 10mg, Stage 2 Vortioxetine 20mg, Stage 2 Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Patients treated with placebo in Stage 1.
Patients treated with vortioxetine 10mg in Stage 1.
Patients treated with vortioxetine 20mg in Stage 1.
Placebo responders from Stage 1 continue on placebo in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 10mg in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 20mg in Stage 2.
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 109 41 34 20 20 12 129 61 46
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-12.4  (1.25) -12.8  (1.99) -11.6  (2.17) -4.1  (1.92) -3.9  (1.98) -2.9  (2.35) -8.3  (1.1) -8.3  (1.4) -7.3  (1.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Combined, Vortioxetine 10mg, Combined
Comments The mean difference between treatment groups was estimated based on LS means for the treatment-by-visit interaction in stagewise MMRM analyses. In each stage, the REML-based MMRM model included site ID (stage 1 only), visit, treatment (placebo, vortioxetine 10mg, vortioxetine 20mg), baseline (for the stage) AISRS total score, treatment-by-visit interaction, and baseline (stage) AISRS total score-by-visit interaction, with an unstructured covariance structure to model the within-patient errors.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9723
Comments [Not Specified]
Method weighed z-score
Comments Equally weighed LS z-score, combining results from stagewise MMRM, was compared to standard normal distribution.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-3.6 to 3.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Combined, Vortioxetine 20mg, Combined
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The mean difference between treatment groups was estimated based on LS means for the treatment-by-visit interaction in stagewise MMRM analyses. In each stage, the REML-based MMRM model included site ID (stage 1 only), visit, treatment (placebo, vortioxetine 10mg, vortioxetine 20mg), baseline (for the stage) AISRS total score, treatment-by-visit interaction, and baseline (stage) AISRS total score-by-visit interaction, with an unstructured covariance structure to model the within-patient errors.
Statistical Test of Hypothesis P-Value 0.6010
Comments [Not Specified]
Method weighed z-score
Comments Equally weighed LS z-score, combining results from stagewise MMRM, was compared to standard normal distribution.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-2.8 to 4.8
Parameter Dispersion
Type: Standard Deviation
Value: 1.9
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index
Hide Description The Metacognition Index (MI) is an index score of the BRIEF-A consisting of 5 scales: initiate, working memory, plan/organise, task monitor, and organization of materials. Each item is rated on a 3-point scale with the numeric score of 1 to 3. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Stage 1 Vortioxetine 10mg, Stage 1 Vortioxetine 20mg, Stage 1 Placebo, Stage 2 Vortioxetine 10mg, Stage 2 Vortioxetine 20mg, Stage 2 Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Patients treated with placebo in Stage 1.
Patients treated with vortioxetine 10mg in Stage 1.
Patients treated with vortioxetine 20mg in Stage 1.
Placebo responders from Stage 1 continue on placebo in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 10mg in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 20mg in Stage 2.
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 107 41 34 20 20 12 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-10.0  (1.26) -11.2  (1.98) -10.2  (2.16) -3.1  (2.28) -2.6  (2.34) 0.9  (2.84) -6.5  (1.3) -6.9  (1.5) -4.6  (1.8)
3.Secondary Outcome
Title Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score
Hide Description BRIEF-A is a validated questionnaire composed of 75-item within nine non-overlapping scales: 4 scales in the Behavioral Regulation Index (BRI) (inhibit, shift, emotional control, and self-monitor), and 5 scales in the Metacognition Index (MI) (initiate, working memory, plan/organise, task monitor, and organization of materials). Each item is rated on a 3-point scale with the numeric score of 1 to 3. The BRIEF-A yields an overall score (Global Executive Composite) composed of two index scores, the MI and the BRI. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Stage 1 Vortioxetine 10mg, Stage 1 Vortioxetine 20mg, Stage 1 Placebo, Stage 2 Vortioxetine 10mg, Stage 2 Vortioxetine 20mg, Stage 2 Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Patients treated with placebo in Stage 1.
Patients treated with vortioxetine 10mg in Stage 1.
Patients treated with vortioxetine 20mg in Stage 1.
Placebo responders from Stage 1 continue on placebo in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 10mg in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 20mg in Stage 2.
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 107 41 34 20 20 12 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-9.9  (1.22) -12.5  (1.93) -11.4  (2.10) -3.0  (2.24) -3.5  (2.31) 2.1  (2.80) -6.5  (1.3) -8.0  (1.5) -4.6  (1.8)
4.Secondary Outcome
Title Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score
Hide Description The SDS comprises a series of patient rated scales designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and 3) home life or family responsibilities are impaired on a 10-point visual analogue scale, on which 0 = normal functioning and 10 = severe functional impairment. The number of days lost and the number of underproductive days last from work/school due to symptoms are also captured. The total score is calculated as a sum of the 3 visual analogue scales, ranges from 0 to 30. A higher score represents more severe functional impairment. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Stage 1 Vortioxetine 10mg, Stage 1 Vortioxetine 20mg, Stage 1 Placebo, Stage 2 Vortioxetine 10mg, Stage 2 Vortioxetine 20mg, Stage 2 Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Patients treated with placebo in Stage 1.
Patients treated with vortioxetine 10mg in Stage 1.
Patients treated with vortioxetine 20mg in Stage 1.
Placebo responders from Stage 1 continue on placebo in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 10mg in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 20mg in Stage 2.
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 92 34 28 18 17 11 110 51 39
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.3  (0.74) -7.9  (1.20) -7.4  (1.29) 0.6  (0.91) -0.9  (0.95) -1.4  (1.14) -2.4  (0.6) -4.4  (0.8) -4.4  (0.9)
5.Secondary Outcome
Title Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score
Hide Description The WLQ is a patient self-rated scale designed to assess on-the-job impact of chronic health problems and/or treatment. The WLQ consists of 25 items in 4 dimensions: limitations handling time (5 items), physical work demands (6 items), mental-interpersonal work demands (9 items), and output demands (5 items). Each item is rated on a 5-point scale from "All of the Time" (score 5) to "None of the Time" (score 0), or "Does Not Apply to My Job". The WLQ Productivity Loss Score is derived from the Global Productivity Index, which is calculated as a weighed sum of the 4 dimensions. Reduction in WLQ Productivity Loss score indicates less work limitation and represents the estimated percentage of productivity loss in the past two weeks due to presenteeism relative to a healthy benchmark sample. WLQ Productivity Loss Score ranges from 0% to 24,9%.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Stage 1 Vortioxetine 10mg, Stage 1 Vortioxetine 20mg, Stage 1 Placebo, Stage 2 Vortioxetine 10mg, Stage 2 Vortioxetine 20mg, Stage 2 Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Patients treated with placebo in Stage 1.
Patients treated with vortioxetine 10mg in Stage 1.
Patients treated with vortioxetine 20mg in Stage 1.
Placebo responders from Stage 1 continue on placebo in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 10mg in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 20mg in Stage 2.
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 91 36 27 15 17 11 106 53 38
Least Squares Mean (Standard Error)
Unit of Measure: percentage of days lost
-2.4  (0.54) -2.5  (0.84) -2.4  (0.96) -0.8  (1.02) -0.9  (0.97) -0.7  (1.20) -1.6  (0.6) -1.7  (0.6) -1.5  (0.8)
6.Secondary Outcome
Title Change in AISRS Inattention Sub-score
Hide Description The AISRS inattentive subscale score consists of 9 items from the AISRS which address inattention. Each item is rated from 0 to 3. The AISRS inattentive subscale score can range from 0 to 27. A higher score corresponds to a worse severity of ADHD inattentiveness.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Stage 1 Vortioxetine 10mg, Stage 1 Vortioxetine 20mg, Stage 1 Placebo, Stage 2 Vortioxetine 10mg, Stage 2 Vortioxetine 20mg, Stage 2 Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Patients treated with placebo in Stage 1.
Patients treated with vortioxetine 10mg in Stage 1.
Patients treated with vortioxetine 20mg in Stage 1.
Placebo responders from Stage 1 continue on placebo in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 10mg in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 20mg in Stage 2.
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 109 41 34 20 20 12 129 61 46
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.5  (0.71) -6.0  (1.14) -5.9  (1.24) -1.9  (1.2) -2.0  (1.21) -1.6  (1.48) -4.2  (0.7) -4.0  (0.8) -3.8  (1.0)
7.Secondary Outcome
Title Change AISRS Hyperactivity/Impulsivity Sub-score
Hide Description The AISRS hyperactive/impulsive subscale score consists of 9 items from the AISRS which address hyperactivity and impulsivity. Each item is rated from 0 to 3. The AISRS hyperactive/impulsive subscale score can range from 0 to 27. A higher score corresponds to a worse severity of ADHD hyperactivity/impulsivity.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Stage 1 Vortioxetine 10mg, Stage 1 Vortioxetine 20mg, Stage 1 Placebo, Stage 2 Vortioxetine 10mg, Stage 2 Vortioxetine 20mg, Stage 2 Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Patients treated with placebo in Stage 1.
Patients treated with vortioxetine 10mg in Stage 1.
Patients treated with vortioxetine 20mg in Stage 1.
Placebo responders from Stage 1 continue on placebo in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 10mg in Stage 2.
Placebo non-responders from Stage 1 re-randomized to treatment with vortioxetine 20mg in Stage 2.
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 109 41 34 20 20 12 129 61 46
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.9  (0.62) -7.0  (0.99) -5.7  (1.08) -2.1  (0.93) -2.0  (0.97) -1.2  (1.15) -4.0  (0.6) -4.5  (0.7) -3.4  (0.8)
8.Secondary Outcome
Title Percentage of Patients Responding (Response Defined as 30% or Greater Reduction From Baseline in AISRS Total Score)
Hide Description AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined response rate was obtained by constructing an equally weighed estimate of the rate combining the two stages.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 145 66 56
Measure Type: Number
Unit of Measure: percentage of participants
30.9 27.5 23.1
9.Secondary Outcome
Title Change in Adult ADHD Self-Report Scale (ASRS) Total Score
Hide Description The Adult ADHD Self-Report Scale (ASRS) is a patient-rated scale designed to assess the ADHD symptoms in adults based on the diagnostic criteria of DSM-IVTM. The ASRS consist of 18 items, each rated on a 5-point scale from "Never" to "Very Often". The categories “Never” and “Rarely” were combined when calculating the total score to mirror the scoring of the AISRS, with 0 representing “Never”/”Rarely” and 3 representing “Very Often”. The Total Score ranges from 0 to 54. A reduction in score indicates less severity of ADHD.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.9  (1.0) -6.5  (1.3) -3.4  (1.4)
10.Secondary Outcome
Title Change in Clinical Global Impression – Severity of Illness (CGI-S) Score
Hide Description The Clinical Global Impression – Severity of Illness (CGI-S) provides the clinician’s impression of the patient’s current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient’s current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 129 61 46
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.5  (0.1) -0.7  (0.1) -0.6  (0.1)
11.Secondary Outcome
Title Clinical Global Impression – Global Improvement (CGI-I) Score
Hide Description The Clinical Global Impression – Global Improvement (CGI-I) provides the clinician’s impression of the patient’s improvement (or worsening). The clinician assesses the patient’s condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicate worsening.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
CGI-I refers to study baseline and was for this reason analyzed for Stage 1 only.
Arm/Group Title Placebo, Stage 1 Vortioxetine 10mg, Stage 1 Vortioxetine 20mg, Stage 1
Hide Arm/Group Description:
Data from patients treated with placebo in Stage
Data from patients treated with vortioxetine 10mg in Stage 1
Data from patients treated with vortioxetine 20mg in Stage 1
Overall Number of Participants Analyzed 124 46 40
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.01  (0.11) 2.93  (0.17) 3.15  (0.18)
12.Secondary Outcome
Title Response (Defined as a CGI-I Score of 1 or 2), Stage 1
Hide Description The Clinical Global Impression – Global Improvement (CGI-I) provides the clinician’s impression of the patient’s improvement (or worsening). The clinician assesses the patient’s condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicate worsening.
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
CGI-I refers to study baseline and was for this reason analyzed for Stage 1 only.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 124 46 40
Measure Type: Number
Unit of Measure: percentages of participants
43 13 11
13.Secondary Outcome
Title Change in BRIEF-A Using the Behavioural Regulation Index
Hide Description The Behavioral Regulation Index (BRI) is an index score of the BRIEF-A and consists of 4 scales: inhibit, shift, emotional control, and self-monitor). Each item is rated on a 3-point scale with the numeric score of 1 to 3. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-5.3  (1.1) -7.9  (1.3) -3.9  (1.6)
14.Secondary Outcome
Title Change in BRIEF-A Subscales - Inhibit
Hide Description The BRIEF-A subscale Inhibit is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 43
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-5.5  (1.4) -8.6  (1.5) -3.2  (1.8)
15.Secondary Outcome
Title Change BRIEF-A Subscales - Initiate
Hide Description The BRIEF-A subscale Initiate is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-6.2  (1.4) -5.8  (1.6) -4.2  (1.8)
16.Secondary Outcome
Title Change in BRIEF-A Subscales - Organization of Materials
Hide Description The BRIEF-A subscale Organization of Materials is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-4.4  (1.1) -6.3  (1.3) -3.2  (1.5)
17.Secondary Outcome
Title Change in BRIEF-A Subscales - Planning/Organize
Hide Description The BRIEF-A subscale Planning/Organize is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-8.2  (1.6) -8.7  (1.8) -6.8  (2.1)
18.Secondary Outcome
Title Change in BRIEF-A Subscales - Shift
Hide Description The BRIEF-A subscale Shift is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-5.6  (1.4) -9.1  (1.6) -3.5  (1.9)
19.Secondary Outcome
Title Change in BRIEF-A Subscales - Self Monitor
Hide Description The BRIEF-A subscale Self Monitor is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-6.5  (1.4) -11.0  (1.6) -4.8  (1.8)
20.Secondary Outcome
Title Change in BRIEF-A Subscales - Task Monitor
Hide Description The BRIEF-A subscale Task Monitor is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-6.4  (1.5) -7.8  (1.7) -4.9  (2.0)
21.Secondary Outcome
Title Change in BRIEF-A Subscales - Working Memory
Hide Description The BRIEF-A subscale Working Memory is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-7.6  (1.6) -9.9  (1.8) -3.8  (2.1)
22.Secondary Outcome
Title Change in BRIEF-A Subscales - Emotional Control
Hide Description The BRIEF-A subscale Emotional Control is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: T-score
-3.4  (1.0) -4.8  (1.1) -3.5  (1.4)
23.Secondary Outcome
Title Change in Perceived Deficits Questionnaire – Depression (PDQ-D) Total Score
Hide Description The PDQ-D is a patient-rated scale designed to assess cognitive impairment/dysfunction adapted for MDD. Each item is rated on a scale from 0 (never) to 4 (almost always). The total score of the 20 items ranges from 0 to 80 with higher scores reflect greater subjective cognitive impairment. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-7.6  (1.6) -9.3  (2.0) -6.3  (2.2)
24.Secondary Outcome
Title Change in PDQ-D Subscales - Attention and Concentration Sub-score
Hide Description The PDQ-D attention/concentration sub-score consists of items 1, 5, 9, 13, and 17 of the PDQ with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.7  (0.4) -2.3  (0.5) -1.8  (0.6)
25.Secondary Outcome
Title Change in PDQ-D Sub-scales - Retrospective Memory Sub-score
Hide Description The PDQ-D retrospective memory sub-score consists of items 2, 6, 10, 14, and 18 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.8  (0.5) -2.4  (0.6) -1.5  (0.6)
26.Secondary Outcome
Title Change in PDQ-D Sub-scales - Prospective Memory Sub-score
Hide Description The PDQ-D prospective memory sub-score consists of items 3, 7, 11, 15, and 19 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.5  (0.4) -2.3  (0.5) -0.9  (0.6)
27.Secondary Outcome
Title Change in PDQ-D Sub-scales - Planning and Organisation Sub-score
Hide Description The PDQ-D planning and organisation sub-score consists of items 4, 8, 12, 16, and 20 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.4  (0.5) -2.5  (0.6) -1.9  (0.7)
28.Secondary Outcome
Title Change in SDS Item Scores - Family
Hide Description The SDS item family is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.5  (0.3) -1.8  (0.3) -1.5  (0.4)
29.Secondary Outcome
Title Change in SDS Item Scores - Work
Hide Description The SDS item work is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 109 50 38
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.2  (0.3) -2.0  (0.4) -2.1  (0.4)
30.Secondary Outcome
Title Change in SDS Item Scores - Social Life
Hide Description The SDS item social life is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.1  (0.3) -1.7  (0.3) -1.5  (0.4)
31.Secondary Outcome
Title Change in SDS Item Scores - Number of Days Lost
Hide Description This SDS item captures days lost from school or work (see outcome 4).
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: days
-0.3  (0.1) -0.2  (0.1) -0.1  (0.2)
32.Secondary Outcome
Title Change in SDS Item Scores - Number of Underproductive Days
Hide Description This SDS item captures the number of underproductive days (see outcome 4)
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 127 61 46
Least Squares Mean (Standard Error)
Unit of Measure: days
-1.2  (0.3) -1.0  (0.3) -1.2  (0.3)
33.Secondary Outcome
Title Change in WLQ Using the Global Productivity Index
Hide Description The WLQ is a patient self-rated scale designed to assess on-the-job impact of chronic health problems and/or treatment. The WLQ consists of 25 items in 4 dimensions: limitations handling time (5 items), physical work demands (6 items), mental-interpersonal work demands (9 items), and output demands (5 items). Each item is rated on a 5-point scale from "All of the Time" (score 5) to "None of the Time" (score 0), or "Does Not Apply to My Job". The Global Productivity Index is calculated as a weighed sum of the 4 dimensions, and ranges from 0.000 to 0.286. Reduction in score indicates less work limitation.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 106 53 37
Least Squares Mean (Standard Error)
Unit of Measure: Index
-0.0  (0.0) -0.0  (0.0) -0.0  (0.0)
34.Secondary Outcome
Title Change in WLQ Domain Scores - Limitations Handling Time
Hide Description Limitations Handling Time is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 117 57 43
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.6  (2.7) -7.7  (3.1) -2.2  (3.7)
35.Secondary Outcome
Title Change in WLQ Domain Scores - Mental-Interpersonal Work Demands
Hide Description Mental-Interpersonal Work Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 126 59 49
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.4  (2.2) -8.2  (2.6) -6.2  (2.9)
36.Secondary Outcome
Title Change in WLQ Domain Scores - Physical Demands
Hide Description Physical Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 115 53 43
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.5  (2.4) -5.0  (2.9) -4.6  (3.2)
37.Secondary Outcome
Title Change in WLQ Domain Scores - Output Demands
Hide Description Output Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 122 57 47
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.9  (3.1) -7.1  (3.5) -7.2  (4.0)
38.Secondary Outcome
Title Change in Adult ADHD Quality of Life Measure (AAQoL) Total Score
Hide Description The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Total score is based on all 29 items and ranges from 29 to 145. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
7.7  (1.7) 9.1  (2.1) 5.4  (2.3)
39.Secondary Outcome
Title Change in AAQoL Subscales - Life Productivity Sub-score
Hide Description The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Life productivity subscale is based on 11 items and ranges from 11 to 55. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
10.9  (2.4) 11.6  (2.8) 6.4  (3.1)
40.Secondary Outcome
Title Change in AAQoL Subscales - Psychological Health Sub-score
Hide Description The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Psychological Health subscale is based on 6 items and ranges from 6 to 30. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6.7  (2.2) 10.3  (2.5) 5.7  (2.7)
41.Secondary Outcome
Title Change in AAQoL Subscales - Life Outlook Sub-score
Hide Description The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Life Outlook subscale is based on 7 items and ranges from 7 to 35. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.7  (1.3) 5.0  (1.7) 3.0  (1.8)
42.Secondary Outcome
Title Change in AAQoL Subscales - Relationships Sub-score
Hide Description The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Relationship subscale is based on 5 items and ranges from 5 to 25. A reduction in score indicates less impairment.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
Arm/Group Title Placebo, Combined Vortioxetine 10mg, Combined Vortioxetine 20mg, Combined
Hide Arm/Group Description:
Combined data from patients treated with placebo in Stage 1 and 2
Combined data from patients treated with vortioxetine 10mg in Stage 1 and 2
Combined data from patients treated with vortioxetine 20mg in Stage 1 and 2
Overall Number of Participants Analyzed 132 62 53
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
7.4  (2.1) 8.1  (2.5) 6.0  (2.7)
Time Frame Baseline to end of study (16 weeks)
Adverse Event Reporting Description Treatment-Emergent Adverse Events are reported in this section
 
Arm/Group Title Placebo-Placebo Vortioxetine 10mg Vortioxetine 20mg
Hide Arm/Group Description Patients randomized to treatment with placebo in Stage 1 and continued on the same treatment in Stage 2. This group consists of placebo responders and placebo non-responders who were re-randomized to Placebo in Stage 2. Patients randomized to treatment with vortioxetine 10mg/day in Stage 1 and continued on the same treatment in Stage 2. In addition, patients that did not respond to placebo in Stage 1 and were re-randomized to treatment with vortioxetine 10mg/day in Stage 2.This group consists of patients who had received dosing of 10 mg vortioxetine in the study. Patients randomized to treatment with vortioxetine 20mg/day in Stage 1 and continued on the same treatment in Stage 2. In addition, patients that did not respond to placebo in Stage 1 and were re-randomized to treatment with vortioxetine 20mg/day in Stage 2. This group consists of patients who had received dosing of 20 mg vortioxetine in the study.
All-Cause Mortality
Placebo-Placebo Vortioxetine 10mg Vortioxetine 20mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/91 (0.00%)   0/68 (0.00%)   0/60 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo-Placebo Vortioxetine 10mg Vortioxetine 20mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/91 (1.10%)   1/68 (1.47%)   0/60 (0.00%) 
Injury, poisoning and procedural complications       
Concussion  1  1/91 (1.10%)  0/68 (0.00%)  0/60 (0.00%) 
Psychiatric disorders       
Suicidal ideation  1  0/91 (0.00%)  1/68 (1.47%)  0/60 (0.00%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo-Placebo Vortioxetine 10mg Vortioxetine 20mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/91 (42.86%)   34/68 (50.00%)   36/60 (60.00%) 
Gastrointestinal disorders       
Abdominal pain upper  1  2/91 (2.20%)  4/68 (5.88%)  0/60 (0.00%) 
Diarrhoea  1  3/91 (3.30%)  4/68 (5.88%)  5/60 (8.33%) 
Nausea  1  3/91 (3.30%)  15/68 (22.06%)  18/60 (30.00%) 
Vomiting  1  1/91 (1.10%)  4/68 (5.88%)  3/60 (5.00%) 
General disorders       
Fatigue  1  10/91 (10.99%)  7/68 (10.29%)  11/60 (18.33%) 
Infections and infestations       
Nasopharyngitis  1  4/91 (4.40%)  2/68 (2.94%)  4/60 (6.67%) 
Investigations       
Weight increased  1  2/91 (2.20%)  5/68 (7.35%)  3/60 (5.00%) 
Nervous system disorders       
Dizziness  1  4/91 (4.40%)  4/68 (5.88%)  2/60 (3.33%) 
Headache  1  17/91 (18.68%)  10/68 (14.71%)  10/60 (16.67%) 
Somnolence  1  3/91 (3.30%)  1/68 (1.47%)  3/60 (5.00%) 
Psychiatric disorders       
Insomnia  1  9/91 (9.89%)  4/68 (5.88%)  5/60 (8.33%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Combined analysis: the overall number of participants analyzed corresponds to the total number of patients in the two stage-wise analyses, where Stage 2 includes patients already included in Stage 1 (patient data not used in the combined analysis).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Email contact via
Organization: H. Lundbeck A/S
Phone: +4536301311
EMail: LundbeckClinicalTrials@lundbeck.com
Layout table for additonal information
Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT02327013     History of Changes
Other Study ID Numbers: 15996A
First Submitted: December 18, 2014
First Posted: December 30, 2014
Results First Submitted: September 27, 2017
Results First Posted: January 31, 2018
Last Update Posted: March 7, 2018