Trial Outcomes & Findings for Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Adults With Major Depressive Disorder (NCT NCT00672958)

Last Updated: 2013-12-13

Results Overview

The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score range is from 0 to 74 where a higher score indicates a greater depressive state. Least squares (LS) means were from an Analysis of Covariance (ANCOVA) model with treatment and center as fixed factors and the baseline value as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

600 participants

Primary outcome timeframe

Baseline and Week 6

Results posted on

2013-12-13

Participant Flow

Participants took part in the study at 47 investigative sites in the United States from 07 April 2008 to 12 November 2008.

Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 2 treatment groups, once a day placebo or 5 mg vortioxetine.

Participant milestones

Participant milestones
Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Study STARTED	300	300
Overall Study Safety Set	298	299
Overall Study Full Analysis Set	286	292
Overall Study COMPLETED	236	244
Overall Study NOT COMPLETED	64	56

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Overall Study Adverse Event	11	9
Overall Study Lack of Efficacy	6	11
Overall Study Non-compliance with study drug	2	3
Overall Study Protocol deviations	11	5
Overall Study Voluntary withdrawal	12	8
Overall Study Lost to Follow-up	22	17
Overall Study Reason not specified	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=300 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=300 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.	Total n=600 Participants Total of all reporting groups
Clinical Global Impression - Severity scale score	4.8 scores on a scale STANDARD_DEVIATION 0.66 • n=5 Participants	4.8 scores on a scale STANDARD_DEVIATION 0.68 • n=7 Participants	4.8 scores on a scale STANDARD_DEVIATION 0.67 • n=5 Participants
Age Continuous	42.4 years STANDARD_DEVIATION 12.70 • n=5 Participants	42.5 years STANDARD_DEVIATION 13.04 • n=7 Participants	42.4 years STANDARD_DEVIATION 12.86 • n=5 Participants
Sex: Female, Male Female	164 Participants n=5 Participants	186 Participants n=7 Participants	350 Participants n=5 Participants
Sex: Female, Male Male	136 Participants n=5 Participants	114 Participants n=7 Participants	250 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian (White, including Hispanic)	216 participants n=5 Participants	209 participants n=7 Participants	425 participants n=5 Participants
Race/Ethnicity, Customized Black	78 participants n=5 Participants	81 participants n=7 Participants	159 participants n=5 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian/ Other Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	36 participants n=5 Participants	34 participants n=7 Participants	70 participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic/Non-Latino	264 participants n=5 Participants	266 participants n=7 Participants	530 participants n=5 Participants
Region of Enrollment United States	300 participants n=5 Participants	300 participants n=7 Participants	600 participants n=5 Participants
Weight	89.53 kg STANDARD_DEVIATION 23.326 • n=5 Participants	86.63 kg STANDARD_DEVIATION 23.528 • n=7 Participants	88.08 kg STANDARD_DEVIATION 23.453 • n=5 Participants
Height	170.36 cm STANDARD_DEVIATION 9.815 • n=5 Participants	168.67 cm STANDARD_DEVIATION 9.815 • n=7 Participants	169.51 cm STANDARD_DEVIATION 9.843 • n=5 Participants
Body Mass Index (BMI)	30.84 kg/m^2 STANDARD_DEVIATION 7.675 • n=5 Participants	30.48 kg/m^2 STANDARD_DEVIATION 8.217 • n=7 Participants	30.66 kg/m^2 STANDARD_DEVIATION 7.946 • n=5 Participants
Waist circumference	97.58 cm STANDARD_DEVIATION 17.757 • n=5 Participants	96.22 cm STANDARD_DEVIATION 18.961 • n=7 Participants	96.90 cm STANDARD_DEVIATION 18.366 • n=5 Participants
Smoking classification Never smoked	119 participants n=5 Participants	123 participants n=7 Participants	242 participants n=5 Participants
Smoking classification Current smoker	124 participants n=5 Participants	116 participants n=7 Participants	240 participants n=5 Participants
Smoking classification Ex-smoker	57 participants n=5 Participants	61 participants n=7 Participants	118 participants n=5 Participants
Alcohol consumption Never	108 participants n=5 Participants	106 participants n=7 Participants	214 participants n=5 Participants
Alcohol consumption Once monthly or less often	102 participants n=5 Participants	124 participants n=7 Participants	226 participants n=5 Participants
Alcohol consumption Once per week	46 participants n=5 Participants	41 participants n=7 Participants	87 participants n=5 Participants
Alcohol consumption 2-to-6 times/week	33 participants n=5 Participants	21 participants n=7 Participants	54 participants n=5 Participants
Alcohol consumption Daily	11 participants n=5 Participants	8 participants n=7 Participants	19 participants n=5 Participants
24-item Hamilton Depression Scale total score	32.2 scores on a scale STANDARD_DEVIATION 5.50 • n=5 Participants	32.7 scores on a scale STANDARD_DEVIATION 5.42 • n=7 Participants	32.5 scores on a scale STANDARD_DEVIATION 5.46 • n=5 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) total score	34.0 scores on a scale STANDARD_DEVIATION 3.41 • n=5 Participants	34.1 scores on a scale STANDARD_DEVIATION 3.39 • n=7 Participants	34.1 scores on a scale STANDARD_DEVIATION 3.40 • n=5 Participants
Hamilton Anxiety Scale Total Score	19.5 scores on a scale STANDARD_DEVIATION 6.19 • n=5 Participants	19.3 scores on a scale STANDARD_DEVIATION 5.24 • n=7 Participants	19.4 scores on a scale STANDARD_DEVIATION 5.73 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: The full analysis set, which includes all randomized participants who received at least 1 dose of study drug and had at least 1 postbaseline value for assessment of primary efficacy. Last observation carried forward (LOCF) was used.

Outcome measures

Outcome measures
Measure	Placebo n=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 6	-13.87 scores on a scale Standard Error 0.662	-14.61 scores on a scale Standard Error 0.650

PRIMARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, 4 and 5

Population: Full analysis set; LOCF 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 ranges from 0 to 74 where a higher score indicates a greater depressive state. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 1 (n=281, 286)	-6.03 scores on a scale Standard Error 0.394	-5.96 scores on a scale Standard Error 0.387
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 2 (n= 286, 291)	-9.30 scores on a scale Standard Error 0.505	-9.05 scores on a scale Standard Error 0.496
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 3 (n= 286, 292)	-11.05 scores on a scale Standard Error 0.545	-11.73 scores on a scale Standard Error 0.536
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 4 (n= 286, 292)	-12.33 scores on a scale Standard Error 0.579	-12.66 scores on a scale Standard Error 0.568
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed Week 5 (n=286, 292)	-13.11 scores on a scale Standard Error 0.628	-13.98 scores on a scale Standard Error 0.617

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, 4, 5 and 6.

Population: Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.

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=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Percentage of Responders in HAM-D24 Total Score by Study Visit Week 1 (n=281, 286)	7.8 percentage of participants	7.0 percentage of participants
Percentage of Responders in HAM-D24 Total Score by Study Visit Week 2 (n=286, 291)	23.8 percentage of participants	21.0 percentage of participants
Percentage of Responders in HAM-D24 Total Score by Study Visit Week 3 (n=286, 292)	31.8 percentage of participants	32.9 percentage of participants
Percentage of Responders in HAM-D24 Total Score by Study Visit Week 4 (n=286, 292)	39.2 percentage of participants	37.0 percentage of participants
Percentage of Responders in HAM-D24 Total Score by Study Visit Week 5 (n=286, 292)	44.4 percentage of participants	43.8 percentage of participants
Percentage of Responders in HAM-D24 Total Score by Study Visit Week 6 (n=286, 292)	46.2 percentage of participants	46.2 percentage of participants

SECONDARY outcome

Timeframe: Week 6

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=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Percentage of Participants in MADRS Remission at Week 6	32.2 percentage of participants	29.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Full analysis set. Participants with missing values were classified as nonsustained responders/remitters.

A sustained response is defined as a ≥20% decrease from Baseline in HAM-D24 total score obtained at Week 1 and sustained through Week 5 and at least 50% decrease from Baseline at Week 6.

Outcome measures

Outcome measures
Measure	Placebo n=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Percentage of Participants With a Sustained Response in HAM-D24	21.0 percentage of participants	19.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, 4, 5 and 6.

Population: Full analysis set. LOCF was used. "n" indicates the number of patients included in the analysis at each time point.

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. Least square means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Week 5 (n=286, 292)	-14.40 scores on a scale Standard Error 0.673	-15.12 scores on a scale Standard Error 0.664
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Week 4 (n=286, 292)	-13.72 scores on a scale Standard Error 0.624	-13.70 scores on a scale Standard Error 0.615
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Week 6 (n=286, 292)	-15.48 scores on a scale Standard Error 0.708	-15.80 scores on a scale Standard Error 0.698
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Week 1 (n=281, 286)	-6.88 scores on a scale Standard Error 0.418	-6.38 scores on a scale Standard Error 0.412
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Week 2 (n=286, 291)	-10.57 scores on a scale Standard Error 0.530	-9.82 scores on a scale Standard Error 0.523
Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Week 3 (n=286, 292)	-12.48 scores on a scale Standard Error 0.583	-12.76 scores on a scale Standard Error 0.575

SECONDARY outcome

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

Population: Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.

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. Least squares means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Week 2 (n=286, 291)	-4.92 scores on a scale Standard Error 0.343	-4.77 scores on a scale Standard Error 0.338
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Week 1 (n=281, 286)	-3.25 scores on a scale Standard Error 0.288	-3.21 scores on a scale Standard Error 0.284
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Week 4 (n=286, 292)	-6.52 scores on a scale Standard Error 0.393	-6.88 scores on a scale Standard Error 0.387
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Week 6 (n=286, 292)	-7.60 scores on a scale Standard Error 0.419	-7.84 scores on a scale Standard Error 0.413

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, 4, 5 and 6.

Population: Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.

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

Outcome measures

Outcome measures
Measure	Placebo n=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Clinical Global Impression Scale-Severity of Illness Week 1 (n=281, 286)	-0.47 scores on a scale Standard Error 0.045	-0.40 scores on a scale Standard Error 0.044
Change From Baseline in Clinical Global Impression Scale-Severity of Illness Week 2 (n=286, 291)	-0.82 scores on a scale Standard Error 0.061	-0.82 scores on a scale Standard Error 0.060
Change From Baseline in Clinical Global Impression Scale-Severity of Illness Week 3 (n=286, 292)	-1.07 scores on a scale Standard Error 0.069	-1.08 scores on a scale Standard Error 0.067
Change From Baseline in Clinical Global Impression Scale-Severity of Illness Week 4 (n=286, 292)	-1.25 scores on a scale Standard Error 0.073	-1.20 scores on a scale Standard Error 0.072
Change From Baseline in Clinical Global Impression Scale-Severity of Illness Week 5 (n=286, 292)	-1.28 scores on a scale Standard Error 0.079	-1.36 scores on a scale Standard Error 0.077
Change From Baseline in Clinical Global Impression Scale-Severity of Illness Week 6 (n=286, 292)	-1.46 scores on a scale Standard Error 0.085	-1.46 scores on a scale Standard Error 0.083

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, 4, 5 and 6.

Population: Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.

The Clinical Global Impression - Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from an ANCOVA model with treatment and center as fixed factors and the CGI-S Baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Clinical Global Impression Scale-Global Improvement Scale Week 4 (n=286, 292)	2.74 scores on a scale Standard Error 0.070	2.75 scores on a scale Standard Error 0.069
Clinical Global Impression Scale-Global Improvement Scale Week 6 (n=286, 292)	2.61 scores on a scale Standard Error 0.076	2.57 scores on a scale Standard Error 0.075
Clinical Global Impression Scale-Global Improvement Scale Week 1 (n=281, 286)	3.38 scores on a scale Standard Error 0.048	3.46 scores on a scale Standard Error 0.047
Clinical Global Impression Scale-Global Improvement Scale Week 2 (n=286, 291)	3.09 scores on a scale Standard Error 0.062	3.08 scores on a scale Standard Error 0.061
Clinical Global Impression Scale-Global Improvement Scale Week 3 (n=286, 292)	2.90 scores on a scale Standard Error 0.066	2.84 scores on a scale Standard Error 0.065
Clinical Global Impression Scale-Global Improvement Scale Week 5 (n=286, 292)	2.74 scores on a scale Standard Error 0.073	2.65 scores on a scale Standard Error 0.071

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 4 and 6.

Population: Full analysis set; LOCF was used. "n" indicates the number of patients included in the analysis at each time point.

The MADRS-S is a patient-reported outcome measure based on MADRS, administered to evaluate treatment effectiveness in depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored between 0 (best) and 3 (worst). The total score is calculated by summing the answers of the nine items, ranging between 0 and 27 (higher scores indicate increased impairment). LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) Week 1 (n=279, 286)	-2.81 scores on a scale Standard Error 0.214	-2.73 scores on a scale Standard Error 0.210
Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) Week 6 (n=284, 292)	-4.56 scores on a scale Standard Error 0.313	-4.97 scores on a scale Standard Error 0.307
Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) Week 4 (n=284, 292)	-4.18 scores on a scale Standard Error 0.272	-4.05 scores on a scale Standard Error 0.267

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set where Baseline SF-36 data were available; LOCF was used.

The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are: 1. Limitation in physical activities because of health problems. 2. Limitations in usual role activities because of physical health problems. 3. Bodily pain. 4. Limitations in social activities because of physical or emotional problems. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perception. Each scale ranges from 0 (best) - 100 (worst). LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=279 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=287 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6 Physical functioning	5.47 scores on a scale Standard Error 1.277	6.87 scores on a scale Standard Error 1.264
Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6 Role - physical	11.73 scores on a scale Standard Error 1.569	14.41 scores on a scale Standard Error 1.549
Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6 Bodily pain	10.77 scores on a scale Standard Error 1.460	10.39 scores on a scale Standard Error 1.445
Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6 General health	7.65 scores on a scale Standard Error 0.985	7.37 scores on a scale Standard Error 0.975
Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6 Vitality	18.00 scores on a scale Standard Error 1.455	17.34 scores on a scale Standard Error 1.440
Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6 Social functioning	21.34 scores on a scale Standard Error 1.687	22.01 scores on a scale Standard Error 1.667
Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6 Role - emotional	19.43 scores on a scale Standard Error 1.756	20.76 scores on a scale Standard Error 1.732
Change From Baseline in 36-item Short-form Health Survey (SF-36) at Week 6 Mental health	18.98 scores on a scale Standard Error 1.401	20.00 scores on a scale Standard Error 1.385

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Full analysis set where data were available; LOCF 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 were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=220 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 6	-6.61 scores on a scale Standard Error 0.548	-6.69 scores on a scale Standard Error 0.557

SECONDARY outcome

Timeframe: Baseline and Week 6

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=286 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=292 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Baseline: Any resource use	82 participants	77 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Baseline: Hospitalization related to depression	1 participants	0 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Baseline: Any sick leave	16 participants	21 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Baseline: Sick leave related to depression	9 participants	13 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Week 6: Any resource use	58 participants	41 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Week 6: Any hospitalization-related service	3 participants	1 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Week 6: Hospitalization related to depression	0 participants	0 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Week 6: Any sick leave	7 participants	7 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Week 6: Sick leave related to depression	3 participants	2 participants
Health Care Resource Utilization as Assessed by the Health Economic Assessment Questionnaire Baseline: Any hospitalization-related services	1 participants	0 participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 142 other events

Deaths: 0 deaths

Vortioxetine

Serious events: 7 serious events

Other events: 168 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=298 participants at risk Vortioxetine placebo-matching capsules, orally, once daily for up to 6 weeks.	Vortioxetine n=299 participants at risk Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 6 weeks.
Immune system disorders Drug hypersensitivity	0.00% 0/298 • 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.	0.33% 1/299 • 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.
Infections and infestations Herpes zoster	0.00% 0/298 • 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.	0.33% 1/299 • 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.
Infections and infestations Puncture site infection	0.34% 1/298 • 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% 0/299 • 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.
Injury, poisoning and procedural complications Injury	0.00% 0/298 • 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.	0.33% 1/299 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/298 • 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.	0.33% 1/299 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.34% 1/298 • 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% 0/299 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/298 • 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.	0.33% 1/299 • 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 Cerebrovascular accident	0.00% 0/298 • 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.	0.33% 1/299 • 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 Convulsion	0.00% 0/298 • 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.	0.33% 1/299 • 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.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.34% 1/298 • 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% 0/299 • 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.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.34% 1/298 • 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% 0/299 • 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