Trial Outcomes & Findings for A Phase 3 Study of Lu AA21004 in Patients With Major Depressive Disorder (NCT NCT02389816)

NCT ID: NCT02389816

Last Updated: 2021-03-24

Results Overview

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 493 participants
• Primary outcome timeframe: Baseline (At the start of double-blind treatment period), up to 8 weeks
• Results posted on: 2021-03-24

Participant Flow

Participants took part in the study at 64 investigative sites in Japan, from 10 April 2015 to 16 March 2018.

Participants with a historical diagnosis of major depressive disorder were enrolled placebo lead-in period for one week prior to randomization, after that participants randomized and enrolled in one of three treatment group (Placebo Group, vortioxetine 10 milligrams (mg) Group, vortioxetine 20 mg Group) for 8 weeks as double-blind treatment period.

Participant milestones

Measure	Placebo Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Study STARTED	164	165	164
Overall Study COMPLETED	149	152	152
Overall Study NOT COMPLETED	15	13	12

Reasons for withdrawal

Measure	Placebo Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Overall Study Randomized but Not Treated	1	0	0
Overall Study Pretreatment Event or Adverse Event (AE)	4	6	7
Overall Study Major Protocol Deviation	1	0	0
Overall Study Lost to Follow-up	1	0	0
Overall Study Withdrawal of Consent	6	4	4
Overall Study Lack of Efficacy	1	0	0
Overall Study Non Compliance with Study Drug	1	1	1
Overall Study Reason not Specified	0	2	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8	Total n=493 Participants Total of all reporting groups
Age, Continuous	39.5 Years STANDARD_DEVIATION 10.47 • n=164 Participants	40.0 Years STANDARD_DEVIATION 10.58 • n=165 Participants	40.4 Years STANDARD_DEVIATION 11.31 • n=164 Participants	40.0 Years STANDARD_DEVIATION 10.78 • n=493 Participants
Sex: Female, Male Female	72 Participants n=164 Participants	72 Participants n=165 Participants	80 Participants n=164 Participants	224 Participants n=493 Participants
Sex: Female, Male Male	92 Participants n=164 Participants	93 Participants n=165 Participants	84 Participants n=164 Participants	269 Participants n=493 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Japan	164 Participants n=164 Participants	165 Participants n=165 Participants	164 Participants n=164 Participants	493 Participants n=493 Participants
Height	166.5 Centimeters (cm) STANDARD_DEVIATION 8.51 • n=164 Participants	165.2 Centimeters (cm) STANDARD_DEVIATION 9.04 • n=165 Participants	164.5 Centimeters (cm) STANDARD_DEVIATION 7.86 • n=164 Participants	165.4 Centimeters (cm) STANDARD_DEVIATION 8.51 • n=493 Participants
Weight	62.44 Kilograms (kg) STANDARD_DEVIATION 12.218 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	61.97 Kilograms (kg) STANDARD_DEVIATION 12.958 • n=165 Participants • The number analyzed is the number of participants with data available for analysis.	61.54 Kilograms (kg) STANDARD_DEVIATION 12.006 • n=164 Participants • The number analyzed is the number of participants with data available for analysis.	61.98 Kilograms (kg) STANDARD_DEVIATION 12.382 • n=492 Participants • The number analyzed is the number of participants with data available for analysis.
Body Mass Index (BMI)	22.44 kg/m^2 STANDARD_DEVIATION 3.450 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	22.56 kg/m^2 STANDARD_DEVIATION 3.560 • n=165 Participants • The number analyzed is the number of participants with data available for analysis.	22.65 kg/m^2 STANDARD_DEVIATION 3.594 • n=164 Participants • The number analyzed is the number of participants with data available for analysis.	22.55 kg/m^2 STANDARD_DEVIATION 3.530 • n=492 Participants • The number analyzed is the number of participants with data available for analysis.
Montgomery Åsberg Depression Rating Scale (MADRS) Total Score	30.5 Scores on a scale STANDARD_DEVIATION 3.87 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	30.8 Scores on a scale STANDARD_DEVIATION 3.73 • n=165 Participants • The number analyzed is the number of participants with data available for analysis.	30.6 Scores on a scale STANDARD_DEVIATION 3.62 • n=164 Participants • The number analyzed is the number of participants with data available for analysis.	30.6 Scores on a scale STANDARD_DEVIATION 3.73 • n=492 Participants • The number analyzed is the number of participants with data available for analysis.
Hamilton Depression Scale (HAM-D17) Total Score	22.0 Scores on a scale STANDARD_DEVIATION 3.19 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	22.1 Scores on a scale STANDARD_DEVIATION 3.10 • n=165 Participants • The number analyzed is the number of participants with data available for analysis.	22.2 Scores on a scale STANDARD_DEVIATION 3.10 • n=164 Participants • The number analyzed is the number of participants with data available for analysis.	22.1 Scores on a scale STANDARD_DEVIATION 3.13 • n=492 Participants • The number analyzed is the number of participants with data available for analysis.
Clinical Global Impressions-Severity (CGI-S) Score	4.5 Scores on a scale STANDARD_DEVIATION 0.63 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	4.5 Scores on a scale STANDARD_DEVIATION 0.63 • n=165 Participants • The number analyzed is the number of participants with data available for analysis.	4.5 Scores on a scale STANDARD_DEVIATION 0.61 • n=164 Participants • The number analyzed is the number of participants with data available for analysis.	4.5 Scores on a scale STANDARD_DEVIATION 0.62 • n=492 Participants • The number analyzed is the number of participants with data available for analysis.
Sheehan Disability Scale (SDS) Total Score	13.9 Scores on a scale STANDARD_DEVIATION 6.22 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	14.0 Scores on a scale STANDARD_DEVIATION 6.00 • n=165 Participants • The number analyzed is the number of participants with data available for analysis.	14.8 Scores on a scale STANDARD_DEVIATION 5.47 • n=164 Participants • The number analyzed is the number of participants with data available for analysis.	14.2 Scores on a scale STANDARD_DEVIATION 5.91 • n=492 Participants • The number analyzed is the number of participants with data available for analysis.
Digit Symbol Substitution Test (DSST) Score	60.2 Scores on a scale STANDARD_DEVIATION 13.93 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	56.8 Scores on a scale STANDARD_DEVIATION 15.15 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	58.0 Scores on a scale STANDARD_DEVIATION 13.72 • n=164 Participants • The number analyzed is the number of participants with data available for analysis.	58.3 Scores on a scale STANDARD_DEVIATION 14.32 • n=490 Participants • The number analyzed is the number of participants with data available for analysis.
Perceived Deficits Questionnaire (PDQ-5) Score	9.0 Scores on a scale STANDARD_DEVIATION 3.54 • n=163 Participants • The number analyzed is the number of participants with data available for analysis.	9.5 Scores on a scale STANDARD_DEVIATION 3.52 • n=165 Participants • The number analyzed is the number of participants with data available for analysis.	9.7 Scores on a scale STANDARD_DEVIATION 3.47 • n=164 Participants • The number analyzed is the number of participants with data available for analysis.	9.4 Scores on a scale STANDARD_DEVIATION 3.52 • n=492 Participants • The number analyzed is the number of participants with data available for analysis.

PRIMARY outcome

Timeframe: Baseline (At the start of double-blind treatment period), up to 8 weeks

Population: Full Analysis Set (FAS): All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period.

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Week 8	-12.37 Scores on a scale Standard Error 0.714	-15.03 Scores on a scale Standard Error 0.699	-15.45 Scores on a scale Standard Error 0.705

SECONDARY outcome

Timeframe: Week 8

Population: FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.

Reported data was percentage of participants who met MADRS response criteria (defined as a ≥50% decrease in the MADRS total score from Baseline) at Week 8 for each group. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
MADRS Response at Week 8 (Last Observation Carried Forward (LOCF))	36.6 Percentage of Participants	47.9 Percentage of Participants	50.6 Percentage of Participants

SECONDARY outcome

Timeframe: Week 8

Population: FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.

Reported data was percentage of participants who met MADRS remission criteria (defined as a MADRS total score ≤10) at Week 8 for each group. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension). MADRS corresponds to core symptoms of depression, and rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
MADRS Remission at Week 8 (LOCF)	21.1 Percentage of Participants	32.1 Percentage of Participants	30.9 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (At the start of double-blind treatment period), up to 8 weeks

Population: FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.

The HAM-D17 is a clinician-rated 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 52 where a higher score indicates a greater depressive state.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Change From Baseline in Hamilton Depression Scale (HAM-D17) Total Score to Week 8 (LOCF)	-8.38 Scores on a scale Standard Error 0.541	-10.19 Scores on a scale Standard Error 0.524	-10.17 Scores on a scale Standard Error 0.532

SECONDARY outcome

Timeframe: Week 8

Population: FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.

The CGI-I assesses the participant's state of mental illness improvement. The participant's condition compared to baseline is rated on a seven-point scale (1=very much improved ~ 7=very much worse). Higher scores indicate greater worsening of illness. Values closest to 1 for this outcome measure indicate the greatest improvement of symptoms.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Clinical Global Impressions-Improvement (CGI-I) Score at Week 8 (LOCF)	2.77 Scores on a scale Standard Error 0.085	2.42 Scores on a scale Standard Error 0.084	2.38 Scores on a scale Standard Error 0.085

SECONDARY outcome

Timeframe: Baseline (At the start of double-blind treatment period), up to 8 weeks

Population: FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.

The CGI-S assesses the impression of the participant's current state of mental illness. The current severity of mental illness is rated on a seven-point scale (1=normal, not ill at all ~ 7=most extremely ill) based on a total clinical experience. Higher scores indicate greater severity of mental illness.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score to Week 8 (LOCF)	-1.19 Scores on a scale Standard Error 0.0088	-1.42 Scores on a scale Standard Error 0.0087	-1.48 Scores on a scale Standard Error 0.0087

SECONDARY outcome

Timeframe: Baseline (At the start of double-blind treatment period), up to 8 weeks

Population: FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.

The SDS 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.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Change From Baseline in Sheehan Disability Scale (SDS) Total Score to Week 8 (LOCF)	-2.85 Scores on a scale Standard Error 0.447	-4.20 Scores on a scale Standard Error 0.432	-4.43 Scores on a scale Standard Error 0.440

SECONDARY outcome

Timeframe: Baseline (At the start of double-blind treatment period), up to 8 weeks

Population: FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.

The DSST is a neuropsychological test to assess cognitive function. Participants are required to copy symbols that are paired with simple geometric shapes or numbers within a specific time for a total possible score of 0 to 133. Higher scores-correct number of symbols reflects greater objective cognitive functioning. An increase in score represents an improvement in an integrated measure of cognitive function.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Change From Baseline in Digit Symbol Substitution Test (DSST) Total Score to Week 8 (LOCF)	4.92 Scores on a scale Standard Error 0.632	4.13 Scores on a scale Standard Error 0.628	4.80 Scores on a scale Standard Error 0.629

SECONDARY outcome

Timeframe: Baseline (At the start of double-blind treatment period), up to 8 weeks

Population: FAS: All participants who were randomized and received at least 1 dose of the study drug in the double-blind treatment period. Here, number analyzed is the number of participants who were evaluable at each category.

PDQ-5 is a self-administered 5-item questionnaire to assess cognition function, including subscales of attention/concentration, retrospective memory, prospective memory, and planning/organization. PDQ-5 total score ranges from 0 to 20 with smaller scores indicate greater cognitive function.

Outcome measures

Measure	Placebo n=164 Participants Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=164 Participants Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Change From Baseline in Perceived Deficits Questionnaire (PDQ-5) Total Score to Week 8 (LOCF)	-1.41 Scores on a scale Standard Error 0.234	-2.28 Scores on a scale Standard Error 0.231	-2.69 Scores on a scale Standard Error 0.234

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Vortioxetine 10 mg

Serious events: 1 serious events

Other events: 54 other events

Deaths: 0 deaths

Vortioxetine 20 mg

Serious events: 3 serious events

Other events: 51 other events

Deaths: 2 deaths

Serious adverse events

Measure	Placebo n=161 participants at risk Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 participants at risk Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=163 participants at risk Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Injury, poisoning and procedural complications Anaesthetic complication	0.00% 0/161 • Up to Week 12 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.	0.00% 0/165 • Up to Week 12 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.	0.61% 1/163 • Up to Week 12 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.
Injury, poisoning and procedural complications Subarachnoid haemorrhage	0.00% 0/161 • Up to Week 12 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.	0.00% 0/165 • Up to Week 12 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.	0.61% 1/163 • Up to Week 12 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.
Nervous system disorders Altered state of consciousness	0.00% 0/161 • Up to Week 12 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.	0.61% 1/165 • Up to Week 12 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.	0.00% 0/163 • Up to Week 12 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.
Nervous system disorders Cerebral haemorrhage	0.00% 0/161 • Up to Week 12 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.	0.00% 0/165 • Up to Week 12 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.	0.61% 1/163 • Up to Week 12 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.
Renal and urinary disorders Nephrolithiasis	0.62% 1/161 • Up to Week 12 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.	0.00% 0/165 • Up to Week 12 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.	0.00% 0/163 • Up to Week 12 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.

Other adverse events

Measure	Placebo n=161 participants at risk Placebo tablets, orally, once daily for up to Week 8	Vortioxetine 10 mg n=165 participants at risk Vortioxetine 10 mg tablets, orally, once daily for up to Week 8	Vortioxetine 20 mg n=163 participants at risk Vortioxetine 10 mg tablets, orally, once daily for up to Week 1, followed by vortioxetine 20 mg tablets, orally, once daily for up to Week 8
Gastrointestinal disorders Nausea	0.62% 1/161 • Up to Week 12 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.	12.7% 21/165 • Up to Week 12 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.	15.3% 25/163 • Up to Week 12 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.
Gastrointestinal disorders Vomiting	0.00% 0/161 • Up to Week 12 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.	5.5% 9/165 • Up to Week 12 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.	3.7% 6/163 • Up to Week 12 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.
Infections and infestations Nasopharyngitis	16.1% 26/161 • Up to Week 12 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.	13.9% 23/165 • Up to Week 12 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.	12.9% 21/163 • Up to Week 12 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.
Nervous system disorders Somnolence	3.7% 6/161 • Up to Week 12 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.	4.2% 7/165 • Up to Week 12 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.	6.7% 11/163 • Up to Week 12 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER