Trial Outcomes & Findings for Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder (NCT NCT00735709)

Last Updated: 2013-12-18

Results Overview

The 24-item Hamilton Depression Scale (HAM-D24) is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score range is from 0 to 74 where a higher score indicates a greater depressive state. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

560 participants

Primary outcome timeframe

Baseline to Week 8

Results posted on

2013-12-18

Participant Flow

Participants took part in the study at 51 investigative sites in Australia, Croatia, France, Germany, Latvia, Lithuania, Malaysia, Netherlands, Poland, Republic of Korea, Russia, South Africa, Taiwan, and Ukraine from 14 August 2008 to 13 August 2009.

Participants with a diagnosis of major depressive disorder were randomized equally in 1 of 4 treatment groups, once daily placebo, 1 mg, 5 mg, or 10 mg vortioxetine.

Participant milestones

Participant milestones
Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Overall Study STARTED	140	140	140	140
Overall Study Treated	140	140	140	139
Overall Study COMPLETED	127	127	129	122
Overall Study NOT COMPLETED	13	13	11	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Overall Study Adverse Event	2	3	1	5
Overall Study Lack of Efficacy	8	4	2	3
Overall Study Noncompliance	0	0	1	0
Overall Study Protocol deviations	1	2	1	1
Overall Study Voluntary Withdrawal	1	3	5	7
Overall Study Lost to Follow-up	0	1	1	1
Overall Study Excluded medication	1	0	0	1

Baseline Characteristics

Efficacy Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=140 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=140 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=140 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=140 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Total n=560 Participants Total of all reporting groups
Age Continuous	46.4 years STANDARD_DEVIATION 12.26 • n=5 Participants	45.4 years STANDARD_DEVIATION 11.89 • n=7 Participants	47.3 years STANDARD_DEVIATION 11.95 • n=5 Participants	46.4 years STANDARD_DEVIATION 12.27 • n=4 Participants	46.4 years STANDARD_DEVIATION 12.08 • n=21 Participants
Age, Customized ≤55 years	103 participants n=5 Participants	110 participants n=7 Participants	102 participants n=5 Participants	107 participants n=4 Participants	422 participants n=21 Participants
Age, Customized >55 years	37 participants n=5 Participants	30 participants n=7 Participants	38 participants n=5 Participants	33 participants n=4 Participants	138 participants n=21 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	93 Participants n=7 Participants	87 Participants n=5 Participants	85 Participants n=4 Participants	351 Participants n=21 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	47 Participants n=7 Participants	53 Participants n=5 Participants	55 Participants n=4 Participants	209 Participants n=21 Participants
Race/Ethnicity, Customized Caucasian	120 participants n=5 Participants	129 participants n=7 Participants	120 participants n=5 Participants	114 participants n=4 Participants	483 participants n=21 Participants
Race/Ethnicity, Customized Black	5 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	10 participants n=21 Participants
Race/Ethnicity, Customized Asian	14 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants	23 participants n=4 Participants	62 participants n=21 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	5 participants n=21 Participants
Race/Ethnicity, Customized Hispanic/Latino	3 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants
Race/Ethnicity, Customized Non-Hispanic/Non-Latino	137 participants n=5 Participants	140 participants n=7 Participants	140 participants n=5 Participants	139 participants n=4 Participants	556 participants n=21 Participants
Region of Enrollment Australia	0 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants
Region of Enrollment Croatia	2 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	1 participants n=4 Participants	13 participants n=21 Participants
Region of Enrollment France	5 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants	13 participants n=21 Participants
Region of Enrollment Germany	63 participants n=5 Participants	50 participants n=7 Participants	64 participants n=5 Participants	56 participants n=4 Participants	233 participants n=21 Participants
Region of Enrollment Latvia	5 participants n=5 Participants	8 participants n=7 Participants	9 participants n=5 Participants	5 participants n=4 Participants	27 participants n=21 Participants
Region of Enrollment Lithuania	4 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	13 participants n=21 Participants
Region of Enrollment Malaysia	7 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	22 participants n=21 Participants
Region of Enrollment Netherlands	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	1 participants n=4 Participants	7 participants n=21 Participants
Region of Enrollment Poland	20 participants n=5 Participants	16 participants n=7 Participants	15 participants n=5 Participants	11 participants n=4 Participants	62 participants n=21 Participants
Region of Enrollment Republic of Korea	7 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants	14 participants n=4 Participants	35 participants n=21 Participants
Region of Enrollment Russia	12 participants n=5 Participants	20 participants n=7 Participants	9 participants n=5 Participants	20 participants n=4 Participants	61 participants n=21 Participants
Region of Enrollment South Africa	5 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	3 participants n=4 Participants	19 participants n=21 Participants
Region of Enrollment Taiwan	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants	4 participants n=21 Participants
Region of Enrollment Ukraine	10 participants n=5 Participants	15 participants n=7 Participants	11 participants n=5 Participants	11 participants n=4 Participants	47 participants n=21 Participants
Weight	75.18 kg STANDARD_DEVIATION 14.924 • n=5 Participants	75.63 kg STANDARD_DEVIATION 17.276 • n=7 Participants	75.41 kg STANDARD_DEVIATION 17.022 • n=5 Participants	74.58 kg STANDARD_DEVIATION 15.190 • n=4 Participants	75.20 kg STANDARD_DEVIATION 16.099 • n=21 Participants
Height	168.70 cm STANDARD_DEVIATION 8.907 • n=5 Participants	168.56 cm STANDARD_DEVIATION 8.264 • n=7 Participants	168.56 cm STANDARD_DEVIATION 9.126 • n=5 Participants	168.70 cm STANDARD_DEVIATION 10.209 • n=4 Participants	168.63 cm STANDARD_DEVIATION 9.129 • n=21 Participants
Body Mass Index (BMI)	26.36 kg/m^2 STANDARD_DEVIATION 4.615 • n=5 Participants	26.53 kg/m^2 STANDARD_DEVIATION 5.380 • n=7 Participants	26.41 kg/m^2 STANDARD_DEVIATION 5.065 • n=5 Participants	26.16 kg/m^2 STANDARD_DEVIATION 4.612 • n=4 Participants	26.36 kg/m^2 STANDARD_DEVIATION 4.917 • n=21 Participants
Smoking Classification Never smoked	88 participants n=5 Participants	74 participants n=7 Participants	88 participants n=5 Participants	79 participants n=4 Participants	329 participants n=21 Participants
Smoking Classification Current smoker	34 participants n=5 Participants	54 participants n=7 Participants	33 participants n=5 Participants	41 participants n=4 Participants	162 participants n=21 Participants
Smoking Classification Ex-smoker	18 participants n=5 Participants	12 participants n=7 Participants	19 participants n=5 Participants	20 participants n=4 Participants	69 participants n=21 Participants
Alcohol Consumption Never	53 participants n=5 Participants	51 participants n=7 Participants	56 participants n=5 Participants	54 participants n=4 Participants	214 participants n=21 Participants
Alcohol Consumption Once monthly or less often	57 participants n=5 Participants	60 participants n=7 Participants	59 participants n=5 Participants	51 participants n=4 Participants	227 participants n=21 Participants
Alcohol Consumption Once per week	16 participants n=5 Participants	13 participants n=7 Participants	9 participants n=5 Participants	16 participants n=4 Participants	54 participants n=21 Participants
Alcohol Consumption 2-to-6 times/week	5 participants n=5 Participants	11 participants n=7 Participants	7 participants n=5 Participants	12 participants n=4 Participants	35 participants n=21 Participants
Alcohol Consumption Daily	9 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants	7 participants n=4 Participants	30 participants n=21 Participants
24-item Hamilton Depression Scale total score	32.7 scores on a scale STANDARD_DEVIATION 4.40 • n=5 Participants	32.5 scores on a scale STANDARD_DEVIATION 5.13 • n=7 Participants	32.1 scores on a scale STANDARD_DEVIATION 5.04 • n=5 Participants	33.1 scores on a scale STANDARD_DEVIATION 4.77 • n=4 Participants	32.6 scores on a scale STANDARD_DEVIATION 4.84 • n=21 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) total score	30.6 scores on a scale STANDARD_DEVIATION 2.89 • n=5 Participants	30.4 scores on a scale STANDARD_DEVIATION 3.01 • n=7 Participants	30.6 scores on a scale STANDARD_DEVIATION 2.83 • n=5 Participants	31.6 scores on a scale STANDARD_DEVIATION 3.83 • n=4 Participants	30.8 scores on a scale STANDARD_DEVIATION 3.19 • n=21 Participants
Hamilton Anxiety Scale total score	19.7 scores on a scale STANDARD_DEVIATION 7.07 • n=5 Participants	20.0 scores on a scale STANDARD_DEVIATION 6.41 • n=7 Participants	19.4 scores on a scale STANDARD_DEVIATION 6.77 • n=5 Participants	21.1 scores on a scale STANDARD_DEVIATION 7.39 • n=4 Participants	20.0 scores on a scale STANDARD_DEVIATION 6.93 • n=21 Participants
Clinical Global Impression - Severity scale score	4.8 scores on a scale STANDARD_DEVIATION 0.80 • n=5 Participants	4.7 scores on a scale STANDARD_DEVIATION 0.73 • n=7 Participants	4.8 scores on a scale STANDARD_DEVIATION 0.73 • n=5 Participants	4.9 scores on a scale STANDARD_DEVIATION 0.76 • n=4 Participants	4.8 scores on a scale STANDARD_DEVIATION 0.76 • n=21 Participants
Hospital Anxiety and Depression (HAD) - Anxiety subscale	11.2 scores on a scale STANDARD_DEVIATION 3.99 • n=5 Participants	11.2 scores on a scale STANDARD_DEVIATION 3.83 • n=7 Participants	11.6 scores on a scale STANDARD_DEVIATION 4.02 • n=5 Participants	11.7 scores on a scale STANDARD_DEVIATION 3.97 • n=4 Participants	11.4 scores on a scale STANDARD_DEVIATION 3.95 • n=21 Participants
Hospital Anxiety and Depression - Depression subscale	13.7 scores on a scale STANDARD_DEVIATION 4.33 • n=5 Participants	13.8 scores on a scale STANDARD_DEVIATION 3.88 • n=7 Participants	13.4 scores on a scale STANDARD_DEVIATION 4.02 • n=5 Participants	13.8 scores on a scale STANDARD_DEVIATION 3.71 • n=4 Participants	13.7 scores on a scale STANDARD_DEVIATION 3.99 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: The full analysis set (FAS) included all patients who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline value for assessment of primary efficacy. A mixed model for repeated measurements (MMRM) based on observed cases was used.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=124 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=129 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=122 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in the 24-item Hamilton Depression Scale Total Score At Week 8	-11.30 scores on a scale Standard Error 0.738	-14.82 scores on a scale Standard Error 0.745	-15.42 scores on a scale Standard Error 0.743	-16.23 scores on a scale Standard Error 0.755

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=90 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=97 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=83 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8	-6.54 scores on a scale Standard Error 0.716	-6.58 scores on a scale Standard Error 0.729	-7.65 scores on a scale Standard Error 0.713	-8.08 scores on a scale Standard Error 0.756

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The Clinical Global Impression - Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=124 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=129 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=122 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Clinical Global Impression Scale-Global Improvement at Week 8	2.84 scores on a scale Standard Error 0.089	2.37 scores on a scale Standard Error 0.090	2.37 scores on a scale Standard Error 0.089	2.29 scores on a scale Standard Error 0.091

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set; last observation carried forward (LOCF) was used.

A responder is defined as a participant with a ≥50% decrease from Baseline in HAM-D24 total score. The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74, where a higher score indicates a greater depressive state.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Percentage of Responders in HAM-D24 Total Score at Week 8	23.0 percentage of participants	47.5 percentage of participants	45.3 percentage of participants	49.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Full analysis set patients with a HAM-A Baseline score ≥ 20. A mixed model for repeated measurements (MMRM) based on observed cases was used.

The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. The Hamilton Anxiety Scale (HAM-A) is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 (symptoms absent) to 56 (severe symptoms). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=65 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=57 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=65 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in HAM-D24 Total Score at Week 8 in Participants With Baseline HAM-A Score ≥20	-11.02 scores on a scale Standard Error 1.017	-15.16 scores on a scale Standard Error 0.991	-15.50 scores on a scale Standard Error 1.063	-15.61 scores on a scale Standard Error 0.984

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set; LOCF was used.

Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Percentage of Participants in MADRS Remission at Week 8	16.5 percentage of participants	25.9 percentage of participants	28.8 percentage of participants	26.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4 and 6

Population: Full analysis set with available data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases was used; "n" indicates the number of patients included in the analysis at each time point.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 6 (n=134, 130, 129, 126)	-10.23 scores on a scale Standard Error 0.690	-13.35 scores on a scale Standard Error 0.695	-13.67 scores on a scale Standard Error 0.697	-15.22 scores on a scale Standard Error 0.705
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 1 (n=139, 137, 138, 138)	-3.47 scores on a scale Standard Error 0.321	-2.81 scores on a scale Standard Error 0.323	-3.20 scores on a scale Standard Error 0.322	-3.20 scores on a scale Standard Error 0.321
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 2 (n=138, 138, 135, 135)	-5.66 scores on a scale Standard Error 0.485	-7.27 scores on a scale Standard Error 0.485	-7.27 scores on a scale Standard Error 0.490	-7.42 scores on a scale Standard Error 0.489
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 4 (n=135, 133, 135, 127)	-8.42 scores on a scale Standard Error 0.634	-11.09 scores on a scale Standard Error 0.637	-11.00 scores on a scale Standard Error 0.639	-11.88 scores on a scale Standard Error 0.646

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2 and 6

Population: Full analysis set with available SDS Total Score data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases was used; "n" indicates the number of patients included in the analysis at each time point.

Outcome measures

Outcome measures
Measure	Placebo n=104 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=103 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=106 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=99 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Other Weeks Assessed Week 1 (n=104, 101, 105, 97)	-1.22 scores on a scale Standard Error 0.392	-1.13 scores on a scale Standard Error 0.399	-1.78 scores on a scale Standard Error 0.393	-1.43 scores on a scale Standard Error 0.403
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Other Weeks Assessed Week 2 (n=102, 101, 100, 96)	-2.53 scores on a scale Standard Error 0.507	-3.44 scores on a scale Standard Error 0.511	-4.14 scores on a scale Standard Error 0.512	-3.40 scores on a scale Standard Error 0.521
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Other Weeks Assessed Week 6 (n=99, 97, 97, 88)	-5.95 scores on a scale Standard Error 0.672	-5.69 scores on a scale Standard Error 0.681	-6.92 scores on a scale Standard Error 0.678	-8.27 scores on a scale Standard Error 0.707

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4 and 6

Population: Full analysis set with available CGI-S data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases was used; "n" indicates the number of patients included in the analysis at each time point.

The Clinical Global Impression - global improvement assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed Week 1 (n=139, 137, 138, 138)	3.65 scores on a scale Standard Error 0.053	3.71 scores on a scale Standard Error 0.054	3.67 scores on a scale Standard Error 0.053	3.64 scores on a scale Standard Error 0.053
Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed Week 4 (n=135, 133, 135, 127)	3.03 scores on a scale Standard Error 0.082	2.69 scores on a scale Standard Error 0.083	2.82 scores on a scale Standard Error 0.083	2.78 scores on a scale Standard Error 0.084
Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed Week 2 (n=138, 138, 135, 135)	3.40 scores on a scale Standard Error 0.069	3.16 scores on a scale Standard Error 0.070	3.19 scores on a scale Standard Error 0.070	3.23 scores on a scale Standard Error 0.070
Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed Week 6 (n=134, 130, 129, 126)	2.95 scores on a scale Standard Error 0.087	2.48 scores on a scale Standard Error 0.088	2.50 scores on a scale Standard Error 0.088	2.37 scores on a scale Standard Error 0.089

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4 and 6

Population: Full analysis set with available data at Week 1; Last observation carried forward (LOCF) was used for other time points. "n" indicates the number of patients included in the analysis at each time point.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Percentage of Responders in HAM-D24 Total Score at Other Weeks Assessed Week 4 (n=139, 139, 139, 139)	18.0 percentage of participants	27.3 percentage of participants	24.5 percentage of participants	26.6 percentage of participants
Percentage of Responders in HAM-D24 Total Score at Other Weeks Assessed Week 6 (n=139, 139, 139, 139)	23.7 percentage of participants	38.1 percentage of participants	36.0 percentage of participants	43.9 percentage of participants
Percentage of Responders in HAM-D24 Total Score at Other Weeks Assessed Week 1 (n=139, 137, 138, 138)	0.7 percentage of participants	0.7 percentage of participants	0.7 percentage of participants	1.4 percentage of participants
Percentage of Responders in HAM-D24 Total Score at Other Weeks Assessed Week 2 (n=139, 139, 139, 139)	5.0 percentage of participants	7.9 percentage of participants	7.2 percentage of participants	8.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4 and 6

Population: Full analysis set patients with a HAM-A Baseline score ≥20 and with available data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases was used; "n" indicates the number of patients included in the analysis at each time point.

The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score range from 0 to 74 where a higher score indicates a greater depressive state. The Hamilton Anxiety Scale (HAM-A) is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 (symptoms absent) to 56 (symptoms severe). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=70 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=62 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=75 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in HAM-D24 Total Score at Other Weeks Assessed in Participants With a Baseline HAM-A Score ≥20 Week 1 (n=66, 70, 62, 75)	-3.79 scores on a scale Standard Error 0.473	-2.94 scores on a scale Standard Error 0.463	-3.55 scores on a scale Standard Error 0.491	-3.19 scores on a scale Standard Error 0.447
Change From Baseline in HAM-D24 Total Score at Other Weeks Assessed in Participants With a Baseline HAM-A Score ≥20 Week 2 (n=65, 70, 59, 72)	-5.76 scores on a scale Standard Error 0.637	-7.21 scores on a scale Standard Error 0.618	-6.58 scores on a scale Standard Error 0.667	-7.74 scores on a scale Standard Error 0.607
Change From Baseline in HAM-D24 Total Score at Other Weeks Assessed in Participants With a Baseline HAM-A Score ≥20 Week 4 (n=64, 68, 60, 69)	-8.56 scores on a scale Standard Error 0.874	-11.41 scores on a scale Standard Error 0.850	-10.20 scores on a scale Standard Error 0.910	-12.06 scores on a scale Standard Error 0.841
Change From Baseline in HAM-D24 Total Score at Other Weeks Assessed in Participants With a Baseline HAM-A Score ≥20 Week 6 (n=64, 67, 57, 68)	-10.25 scores on a scale Standard Error 0.958	-13.68 scores on a scale Standard Error 0.932	-13.23 scores on a scale Standard Error 1.002	-15.10 scores on a scale Standard Error 0.923

SECONDARY outcome

Timeframe: Weeks 1, 2, 4 and 6

Population: Full analysis set with available data at Week 1; Last observation carried forward was used for other time points.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Percentage of Participants in MADRS Remission at Other Weeks Assessed Week 1 (n=139, 137, 138, 138)	0.7 percentage of participants	0.7 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants in MADRS Remission at Other Weeks Assessed Week 2 (n=139, 139, 139, 139)	2.2 percentage of participants	2.2 percentage of participants	1.4 percentage of participants	1.4 percentage of participants
Percentage of Participants in MADRS Remission at Other Weeks Assessed Week 4 (n=139, 139, 139, 139)	6.5 percentage of participants	11.5 percentage of participants	11.5 percentage of participants	10.8 percentage of participants
Percentage of Participants in MADRS Remission at Other Weeks Assessed Week 6 (n=139, 139, 139, 139)	10.1 percentage of participants	20.1 percentage of participants	20.9 percentage of participants	22.3 percentage of participants

SECONDARY outcome

Timeframe: From Baseline through Week 8

Population: Full analysis set

A sustained response is defined as a ≥20% decrease from Baseline in HAM-D24 total score obtained at Week 1 and sustained through Week 7 and at least 50% decrease from Baseline at Week 8.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Percentage of Participants With a Sustained Response in HAM-D24 Total Score	10.1 percentage of participants	9.4 percentage of participants	10.1 percentage of participants	10.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 6, and 8

The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score at Each Week Week 8 (n=128, 124, 129, 122)	-10.91 scores on a scale Standard Error 0.708	-14.89 scores on a scale Standard Error 0.715	-15.09 scores on a scale Standard Error 0.712	-15.65 scores on a scale Standard Error 0.728
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score at Each Week Week 1 (n=139, 137, 138, 138)	-2.90 scores on a scale Standard Error 0.324	-2.55 scores on a scale Standard Error 0.326	-2.66 scores on a scale Standard Error 0.324	-2.57 scores on a scale Standard Error 0.328
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score at Each Week Week 2 (n=138, 138, 135, 135)	-4.92 scores on a scale Standard Error 0.463	-6.65 scores on a scale Standard Error 0.463	-6.40 scores on a scale Standard Error 0.467	-6.51 scores on a scale Standard Error 0.472
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score at Each Week Week 4 (n=135, 133, 135, 127)	-7.85 scores on a scale Standard Error 0.619	-10.79 scores on a scale Standard Error 0.622	-10.30 scores on a scale Standard Error 0.622	-10.89 scores on a scale Standard Error 0.635
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score at Each Week Week 6 (n=134, 130, 129, 126)	-9.72 scores on a scale Standard Error 0.675	-13.16 scores on a scale Standard Error 0.680	-13.10 scores on a scale Standard Error 0.680	-14.19 scores on a scale Standard Error 0.694

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 6, and 8

The HAM-A is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 to 56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety. LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Each Week Assessed Week 6 (n=134, 130, 129, 126)	-5.44 scores on a scale Standard Error 0.471	-7.29 scores on a scale Standard Error 0.475	-7.21 scores on a scale Standard Error 0.476	-8.33 scores on a scale Standard Error 0.483
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Each Week Assessed Week 8 (n=128, 124, 129, 122)	-5.98 scores on a scale Standard Error 0.498	-8.08 scores on a scale Standard Error 0.503	-8.11 scores on a scale Standard Error 0.501	-8.86 scores on a scale Standard Error 0.511
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Each Week Assessed Week 1 (n=139, 137, 138, 138)	-1.58 scores on a scale Standard Error 0.260	-1.27 scores on a scale Standard Error 0.261	-1.41 scores on a scale Standard Error 0.261	-1.56 scores on a scale Standard Error 0.261
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Each Week Assessed Week 2 (n=138, 138, 135, 135)	-3.06 scores on a scale Standard Error 0.343	-3.72 scores on a scale Standard Error 0.343	-3.09 scores on a scale Standard Error 0.346	-3.77 scores on a scale Standard Error 0.347
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Each Week Assessed Week 4 (n=135, 133, 135, 127)	-4.54 scores on a scale Standard Error 0.416	-5.95 scores on a scale Standard Error 0.418	-5.60 scores on a scale Standard Error 0.418	-6.11 scores on a scale Standard Error 0.425

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 6, and 8

The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 1 (n=139, 137, 138, 138)	-0.24 scores on a scale Standard Error 0.044	-0.20 scores on a scale Standard Error 0.045	-0.22 scores on a scale Standard Error 0.044	-0.24 scores on a scale Standard Error 0.044
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 8 (n=128, 124, 129, 122)	-1.12 scores on a scale Standard Error 0.101	-1.50 scores on a scale Standard Error 0.102	-1.63 scores on a scale Standard Error 0.101	-1.74 scores on a scale Standard Error 0.103
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 2 (n=138, 138, 135, 135)	-0.46 scores on a scale Standard Error 0.062	-0.58 scores on a scale Standard Error 0.062	-0.61 scores on a scale Standard Error 0.062	-0.60 scores on a scale Standard Error 0.062
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 4 (n=135, 133, 135, 127)	-0.75 scores on a scale Standard Error 0.080	-1.07 scores on a scale Standard Error 0.081	-1.10 scores on a scale Standard Error 0.081	-1.06 scores on a scale Standard Error 0.082
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 6 (n=134, 130, 129, 126)	-0.96 scores on a scale Standard Error 0.092	-1.41 scores on a scale Standard Error 0.093	-1.38 scores on a scale Standard Error 0.093	-1.55 scores on a scale Standard Error 0.094

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 4, and 8

The HAD scale is completed by the participant and comprises two subscales, one measuring depression (focusing on the state of lost interest and diminished pleasure response) and one measuring anxiety (including anxious mood, restlessness, anxious thoughts, panic attacks). Each subscale is made up of 7 items that are assessed on a scale of 0 = no anxiety/depression to 3 = severe feeling of anxiety/depression. Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. Scores for the depression and anxiety subscales are summed separately and not combined, with each score ranging from 0 to 21 (maximal severity). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=138 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales at Each Week Assessed Anxiety Scale at Week 8 (n=129, 129, 127, 122)	-2.55 scores on a scale Standard Error 0.315	-3.79 scores on a scale Standard Error 0.315	-3.70 scores on a scale Standard Error 0.317	-4.38 scores on a scale Standard Error 0.321
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales at Each Week Assessed Depression Scale at Week 1 (n=139, 137, 138, 137)	-0.32 scores on a scale Standard Error 0.217	-0.90 scores on a scale Standard Error 0.217	-0.74 scores on a scale Standard Error 0.216	-0.92 scores on a scale Standard Error 0.218
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales at Each Week Assessed Depression Scale at Week 4 (n=137, 138, 135, 134)	-2.32 scores on a scale Standard Error 0.348	-3.45 scores on a scale Standard Error 0.347	-3.32 scores on a scale Standard Error 0.350	-3.80 scores on a scale Standard Error 0.352
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales at Each Week Assessed Depression Scale at Week 8 (n=129, 129, 127, 122)	-3.19 scores on a scale Standard Error 0.392	-4.67 scores on a scale Standard Error 0.393	-5.02 scores on a scale Standard Error 0.396	-5.49 scores on a scale Standard Error 0.401
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales at Each Week Assessed Anxiety Scale at Week 1 (n=139, 137, 138, 137)	-0.46 scores on a scale Standard Error 0.190	-1.14 scores on a scale Standard Error 0.190	-0.87 scores on a scale Standard Error 0.189	-0.91 scores on a scale Standard Error 0.190
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales at Each Week Assessed Anxiety Scale at Week 4 (n=137, 138, 135, 134)	-1.95 scores on a scale Standard Error 0.277	-2.83 scores on a scale Standard Error 0.276	-2.81 scores on a scale Standard Error 0.278	-2.80 scores on a scale Standard Error 0.279

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4 and 8

Population: Full analysis set with available SF-36 Subscore data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases was used; "n" indicates the number of patients included in the analysis at each time point.

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The physical functioning subscale assesses limitations in physical activities because of health problems. The sub-score scale ranges from 0 (best) - 100 (worst). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=137 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=136 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Functioning Subscore at All Weeks Assessed Week 2 (n=138,139,136,136)	2.24 scores on a scale Standard Error 1.279	5.39 scores on a scale Standard Error 1.273	7.55 scores on a scale Standard Error 1.285	3.34 scores on a scale Standard Error 1.289
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Functioning Subscore at All Weeks Assessed Week 4 (n=135,132,135,128)	5.10 scores on a scale Standard Error 1.354	7.77 scores on a scale Standard Error 1.364	9.35 scores on a scale Standard Error 1.356	6.92 scores on a scale Standard Error 1.385
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Functioning Subscore at All Weeks Assessed Week 8 (n=129,129,128,122)	8.77 scores on a scale Standard Error 1.407	9.59 scores on a scale Standard Error 1.408	12.31 scores on a scale Standard Error 1.411	11.28 scores on a scale Standard Error 1.441

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4 and 8

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The role-physical subscale assesses limitations in usual role activities because of physical health problems. The sub-score scale ranges from 0 (best) - 100 (worst). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=137 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=136 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Physical Subscore at All Weeks Assessed Week 2 (n=138, 139, 136, 136)	0.74 scores on a scale Standard Error 1.511	6.09 scores on a scale Standard Error 1.505	7.38 scores on a scale Standard Error 1.520	5.00 scores on a scale Standard Error 1.525
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Physical Subscore at All Weeks Assessed Week 4 (n=135, 132, 135, 128)	4.53 scores on a scale Standard Error 1.706	10.62 scores on a scale Standard Error 1.721	12.97 scores on a scale Standard Error 1.709	8.28 scores on a scale Standard Error 1.748
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Physical Subscore at All Weeks Assessed Week 8 (n=129, 129, 128, 122)	8.46 scores on a scale Standard Error 1.830	14.09 scores on a scale Standard Error 1.833	15.64 scores on a scale Standard Error 1.835	15.76 scores on a scale Standard Error 1.878

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4 and 8

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The bodily pain sub-score scale ranges from 0 (best) - 100 (worst). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=137 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=136 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Bodily Pain Subscore at All Weeks Assessed Week 8 (n=129, 129, 128, 122)	7.17 scores on a scale Standard Error 1.920	11.99 scores on a scale Standard Error 1.920	9.63 scores on a scale Standard Error 1.928	12.89 scores on a scale Standard Error 1.970
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Bodily Pain Subscore at All Weeks Assessed Week 2 (n=138, 139, 136, 136)	2.99 scores on a scale Standard Error 1.630	5.06 scores on a scale Standard Error 1.624	4.52 scores on a scale Standard Error 1.644	7.22 scores on a scale Standard Error 1.644
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Bodily Pain Subscore at All Weeks Assessed Week 4 (n=135, 132, 135, 128)	4.45 scores on a scale Standard Error 1.738	5.33 scores on a scale Standard Error 1.752	7.75 scores on a scale Standard Error 1.744	10.66 scores on a scale Standard Error 1.778

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4 and 8

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The general health sub-score scale ranges from 0 (best) - 100 (worst). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=137 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=136 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) General Health Subscore at All Weeks Assessed Week 2 (n=138, 139, 136, 136)	2.83 scores on a scale Standard Error 1.048	5.54 scores on a scale Standard Error 1.044	5.64 scores on a scale Standard Error 1.054	5.47 scores on a scale Standard Error 1.056
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) General Health Subscore at All Weeks Assessed Week 4 (n=135, 132, 135, 128)	6.51 scores on a scale Standard Error 1.235	8.98 scores on a scale Standard Error 1.245	9.96 scores on a scale Standard Error 1.238	10.99 scores on a scale Standard Error 1.263
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) General Health Subscore at All Weeks Assessed Week 8 (n=129, 129, 128, 121)	8.68 scores on a scale Standard Error 1.392	12.46 scores on a scale Standard Error 1.395	13.67 scores on a scale Standard Error 1.396	13.87 scores on a scale Standard Error 1.429

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4 and 8

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The vitality sub-score assesses energy and fatigue, and ranges from 0 (best) - 100 (worst). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=137 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=136 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Vitality Subscore at All Weeks Assessed Week 2 (n=138, 139, 136, 136)	5.97 scores on a scale Standard Error 1.199	10.39 scores on a scale Standard Error 1.193	8.83 scores on a scale Standard Error 1.205	8.03 scores on a scale Standard Error 1.208
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Vitality Subscore at All Weeks Assessed Week 4 (n=135, 132, 135, 128)	12.06 scores on a scale Standard Error 1.523	16.69 scores on a scale Standard Error 1.536	16.04 scores on a scale Standard Error 1.526	16.07 scores on a scale Standard Error 1.560
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Vitality Subscore at All Weeks Assessed Week 8 (n=129, 129, 128, 122)	16.14 scores on a scale Standard Error 1.748	22.34 scores on a scale Standard Error 1.752	21.21 scores on a scale Standard Error 1.753	24.17 scores on a scale Standard Error 1.793

SECONDARY outcome

Timeframe: Baseline and Weeks 2 and 4

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The social functioning subscale assesses limitations in social activities because of physical or emotional problems. The sub-score scale ranges from 0 (best) - 100 (worst). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=137 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=136 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Social Functioning Subscore at Other Weeks Assessed Week 2 (n=138, 139, 136, 136)	6.38 scores on a scale Standard Error 1.479	9.71 scores on a scale Standard Error 1.473	12.02 scores on a scale Standard Error 1.486	10.03 scores on a scale Standard Error 1.491
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Social Functioning Subscore at Other Weeks Assessed Week 4 (n=135, 132, 135, 128)	12.34 scores on a scale Standard Error 1.760	15.71 scores on a scale Standard Error 1.775	18.57 scores on a scale Standard Error 1.762	15.84 scores on a scale Standard Error 1.804
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Social Functioning Subscore at Other Weeks Assessed Week 8 (n=129, 129, 128, 122)	15.60 scores on a scale Standard Error 1.989	21.71 scores on a scale Standard Error 1.991	21.87 scores on a scale Standard Error 1.993	24.94 scores on a scale Standard Error 2.040

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4 and 8

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The role-emotional subscale assesses limitations in usual role activities because of emotional problems. The sub-score scale ranges from 0 (best) - 100 (worst). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=137 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=136 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Emotional Subscore at All Weeks Assessed Week 2 (n=138, 139, 136, 136)	6.84 scores on a scale Standard Error 1.570	8.78 scores on a scale Standard Error 1.563	10.87 scores on a scale Standard Error 1.579	9.93 scores on a scale Standard Error 1.581
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Emotional Subscore at All Weeks Assessed Week 4 (n=135, 132, 135, 128)	12.05 scores on a scale Standard Error 1.755	17.01 scores on a scale Standard Error 1.772	18.08 scores on a scale Standard Error 1.758	14.58 scores on a scale Standard Error 1.797
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Role-Emotional Subscore at All Weeks Assessed Week 8 (n=129, 129, 128, 122)	15.96 scores on a scale Standard Error 1.941	23.06 scores on a scale Standard Error 1.946	22.89 scores on a scale Standard Error 1.947	24.71 scores on a scale Standard Error 1.990

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4 and 8

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The mental health sub-score assesses general mental health (psychological distress and well-being) and ranges from 0 (best) - 100 (worst). LS means are from a mixed model for repeated measurements (MMRM) with Baseline-by-week, center, week, and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=137 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=136 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Mental Health Subscore at All Weeks Assessed Week 2 (n=138, 139, 136, 136)	6.98 scores on a scale Standard Error 1.199	10.62 scores on a scale Standard Error 1.192	9.56 scores on a scale Standard Error 1.205	10.26 scores on a scale Standard Error 1.207
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Mental Health Subscore at All Weeks Assessed Week 4 (n= 135, 132, 135, 128)	13.06 scores on a scale Standard Error 1.418	16.78 scores on a scale Standard Error 1.429	16.56 scores on a scale Standard Error 1.421	16.38 scores on a scale Standard Error 1.451
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Mental Health Subscore at All Weeks Assessed Week 8 (n=129, 129, 128, 122)	16.28 scores on a scale Standard Error 1.625	23.61 scores on a scale Standard Error 1.628	22.24 scores on a scale Standard Error 1.631	24.89 scores on a scale Standard Error 1.667

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set

Healthcare resource utilization was assessed by the Health Economic Assessment (HEA) questionnaire, which monitors the participants' absenteeism from work, as well as resource use such as visits to a general practitioner, outpatient and inpatient services, hospitalization, medications, and other relevant services over the past 8 weeks.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=139 Participants Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=139 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 Participants Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Baseline: Any resource use	62 participants	64 participants	71 participants	61 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Baseline: Hospitalization related to depression	3 participants	3 participants	4 participants	2 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Week 8: Any resource use	31 participants	13 participants	25 participants	25 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Week 8: Any sick leave	16 participants	6 participants	11 participants	18 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Baseline: Any hospitalization-related services	4 participants	3 participants	6 participants	4 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Baseline: Any sick leave	17 participants	7 participants	14 participants	21 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Baseline: Sick leave related to depression	12 participants	6 participants	10 participants	18 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Week 8: Any hospitalization-related service	3 participants	0 participants	1 participants	2 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Week 8: Hospitalization related to depression	0 participants	0 participants	1 participants	0 participants
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire. Week 8: Sick leave related to depression	13 participants	6 participants	9 participants	14 participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 39 other events

Deaths: 0 deaths

Vortioxetine 1 mg

Serious events: 1 serious events

Other events: 36 other events

Deaths: 0 deaths

Vortioxetine 5 mg

Serious events: 1 serious events

Other events: 56 other events

Deaths: 0 deaths

Vortioxetine 10 mg

Serious events: 2 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=140 participants at risk Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 1 mg n=140 participants at risk Vortioxetine 1 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 5 mg n=140 participants at risk Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up 8 weeks.	Vortioxetine 10 mg n=139 participants at risk Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up 8 weeks.
Cardiac disorders Tachycardia	0.00% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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.	0.71% 1/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/139 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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 Pancreatitis	0.71% 1/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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.	0.72% 1/139 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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 Dizziness	0.71% 1/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/139 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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.
Psychiatric disorders Suicide attempt	0.00% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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.	0.72% 1/139 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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.
Vascular disorders Hypertensive crisis	0.00% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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.	0.71% 1/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/140 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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% 0/139 • Treatment-emergent adverse events are defined as adverse events whose onset occurred or intensity increased after the first dose of double-blind study drug through 30 days after permanent discontinuation of double-blind study drug. 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

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: [email protected]

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