Trial Outcomes & Findings for Study of Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder (NCT NCT00731120)

Last Updated: 2013-12-18

Results Overview

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 (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

457 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2013-12-18

Participant Flow

Participants took part in the study at 41 investigative sites in the United States from 17 June 2008 to 16 February 2009.

Participants with a diagnosis of generalized anxiety disorder were enrolled equally in one of three treatment groups, once a day placebo or 2.5 or 10 mg vortioxetine.

Participant milestones

Participant milestones
Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Overall Study STARTED	153	152	152
Overall Study Treated	153	151	152
Overall Study COMPLETED	111	109	116
Overall Study NOT COMPLETED	42	43	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Overall Study Adverse Event	7	6	8
Overall Study Lack of Efficacy	4	5	4
Overall Study Noncompliance with Study Drug	3	3	1
Overall Study Protocol Deviations	1	6	1
Overall Study Withdrawal of Consent	13	8	4
Overall Study Lost to Follow-up	10	15	17
Overall Study Other	4	0	1

Baseline Characteristics

Study of Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=153 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=152 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=152 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.	Total n=457 Participants Total of all reporting groups
Age Continuous	39.5 years STANDARD_DEVIATION 13.45 • n=93 Participants	40.8 years STANDARD_DEVIATION 13.81 • n=4 Participants	43.3 years STANDARD_DEVIATION 14.99 • n=27 Participants	41.2 years STANDARD_DEVIATION 14.15 • n=483 Participants
Age, Customized ≤55 years	136 participants n=93 Participants	127 participants n=4 Participants	120 participants n=27 Participants	383 participants n=483 Participants
Age, Customized >55 years	17 participants n=93 Participants	25 participants n=4 Participants	32 participants n=27 Participants	74 participants n=483 Participants
Sex: Female, Male Female	105 Participants n=93 Participants	103 Participants n=4 Participants	96 Participants n=27 Participants	304 Participants n=483 Participants
Sex: Female, Male Male	48 Participants n=93 Participants	49 Participants n=4 Participants	56 Participants n=27 Participants	153 Participants n=483 Participants
Race/Ethnicity, Customized Hispanic/Latino	13 participants n=93 Participants	18 participants n=4 Participants	15 participants n=27 Participants	46 participants n=483 Participants
Race/Ethnicity, Customized Non-Hispanic/Non-Latino	140 participants n=93 Participants	134 participants n=4 Participants	137 participants n=27 Participants	411 participants n=483 Participants
Race/Ethnicity, Customized Caucasian (White, including Hispanic)	105 participants n=93 Participants	110 participants n=4 Participants	112 participants n=27 Participants	327 participants n=483 Participants
Race/Ethnicity, Customized Black	46 participants n=93 Participants	38 participants n=4 Participants	38 participants n=27 Participants	122 participants n=483 Participants
Race/Ethnicity, Customized Asian	2 participants n=93 Participants	3 participants n=4 Participants	2 participants n=27 Participants	7 participants n=483 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Region of Enrollment United States	153 participants n=93 Participants	152 participants n=4 Participants	152 participants n=27 Participants	457 participants n=483 Participants
Weight	82.66 kg STANDARD_DEVIATION 20.731 • n=93 Participants	84.48 kg STANDARD_DEVIATION 22.727 • n=4 Participants	85.67 kg STANDARD_DEVIATION 23.249 • n=27 Participants	84.27 kg STANDARD_DEVIATION 22.245 • n=483 Participants
Height	168.31 cm STANDARD_DEVIATION 9.994 • n=93 Participants	168.63 cm STANDARD_DEVIATION 8.932 • n=4 Participants	168.86 cm STANDARD_DEVIATION 10.032 • n=27 Participants	168.60 cm STANDARD_DEVIATION 9.649 • n=483 Participants
Body Mass Index (BMI)	29.10 kg/m^2 STANDARD_DEVIATION 6.595 • n=93 Participants	29.69 kg/m^2 STANDARD_DEVIATION 7.817 • n=4 Participants	30.04 kg/m^2 STANDARD_DEVIATION 7.792 • n=27 Participants	29.61 kg/m^2 STANDARD_DEVIATION 7.415 • n=483 Participants
Smoking Classification Never Smoked	87 participants n=93 Participants	72 participants n=4 Participants	84 participants n=27 Participants	243 participants n=483 Participants
Smoking Classification Current smoker	44 participants n=93 Participants	51 participants n=4 Participants	46 participants n=27 Participants	141 participants n=483 Participants
Smoking Classification Ex-smoker	22 participants n=93 Participants	29 participants n=4 Participants	22 participants n=27 Participants	73 participants n=483 Participants
Alcohol Consumption Never	50 participants n=93 Participants	42 participants n=4 Participants	44 participants n=27 Participants	136 participants n=483 Participants
Alcohol Consumption Once monthly or less often	52 participants n=93 Participants	54 participants n=4 Participants	56 participants n=27 Participants	162 participants n=483 Participants
Alcohol Consumption Once a week	33 participants n=93 Participants	28 participants n=4 Participants	29 participants n=27 Participants	90 participants n=483 Participants
Alcohol Consumption 2 to 6 times per week	17 participants n=93 Participants	23 participants n=4 Participants	22 participants n=27 Participants	62 participants n=483 Participants
Alcohol Consumption Daily	1 participants n=93 Participants	5 participants n=4 Participants	1 participants n=27 Participants	7 participants n=483 Participants
Hamilton Anxiety Scale Total Score	25.2 scores on a scale STANDARD_DEVIATION 3.86 • n=93 Participants	25.0 scores on a scale STANDARD_DEVIATION 3.60 • n=4 Participants	24.5 scores on a scale STANDARD_DEVIATION 3.71 • n=27 Participants	24.9 scores on a scale STANDARD_DEVIATION 3.73 • n=483 Participants
Clinical Global Impression - Severity scale score	4.4 scores on a scale STANDARD_DEVIATION 0.54 • n=93 Participants	4.3 scores on a scale STANDARD_DEVIATION 0.49 • n=4 Participants	4.3 scores on a scale STANDARD_DEVIATION 0.47 • n=27 Participants	4.3 scores on a scale STANDARD_DEVIATION 0.50 • n=483 Participants
Hospital Anxiety and Depression - Anxiety subscale	13.9 scores on a scale STANDARD_DEVIATION 3.27 • n=93 Participants	13.2 scores on a scale STANDARD_DEVIATION 3.56 • n=4 Participants	13.2 scores on a scale STANDARD_DEVIATION 3.17 • n=27 Participants	13.4 scores on a scale STANDARD_DEVIATION 3.35 • n=483 Participants
Hospital Anxiety and Depression - Depression subscale	8.7 scores on a scale STANDARD_DEVIATION 3.67 • n=93 Participants	8.0 scores on a scale STANDARD_DEVIATION 3.80 • n=4 Participants	8.0 scores on a scale STANDARD_DEVIATION 3.60 • n=27 Participants	8.3 scores on a scale STANDARD_DEVIATION 3.70 • n=483 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) total score	12.73 scores on a scale STANDARD_DEVIATION 2.417 • n=93 Participants	12.64 scores on a scale STANDARD_DEVIATION 2.502 • n=4 Participants	13.04 scores on a scale STANDARD_DEVIATION 2.521 • n=27 Participants	12.80 scores on a scale STANDARD_DEVIATION 2.481 • n=483 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The full analysis set (FAS) included all randomized patients who received at least 1 dose of study drug, and had at least 1 post-baseline value for assessment of primary efficacy. Last observation carried forward (LOCF) was used.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=144 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=146 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score	-9.87 scores on a scale Standard Error 0.584	-10.75 scores on a scale Standard Error 0.569	-10.68 scores on a scale Standard Error 0.581

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. 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=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=144 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=146 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed Week 1 (n=147, 142, 143)	-5.07 scores on a scale Standard Error 0.433	-5.29 scores on a scale Standard Error 0.423	-5.30 scores on a scale Standard Error 0.433
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed Week 2 (n=148, 144, 146)	-7.41 scores on a scale Standard Error 0.501	-8.11 scores on a scale Standard Error 0.488	-8.05 scores on a scale Standard Error 0.499
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed Week 4 (n=148, 144, 146)	-8.88 scores on a scale Standard Error 0.566	-9.45 scores on a scale Standard Error 0.551	-9.54 scores on a scale Standard Error 0.564
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed Week 6 (n=148, 144, 146)	-9.54 scores on a scale Standard Error 0.565	-10.35 scores on a scale Standard Error 0.550	-10.50 scores on a scale Standard Error 0.563

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set; LOCF was used.

Response was defined as a participant with a ≥50% decrease from Baseline in the HAM-A total score. 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 (symptoms absent) to 56 (maximum severity).

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=144 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=146 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Percentage of Responders in HAM-A Total Score at Week 8	41.9 percentage of participants	46.5 percentage of participants	41.8 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Full analysis set; LOCF was used.

Remission is defined as a Hamilton Anxiety Scale (HAM-A) total score ≤ 7. 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 (symptoms absent) to 56 (maximum severity).

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=144 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=146 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Percentage of Participants in HAM-A Remission at Week 8	21.6 percentage of participants	21.5 percentage of participants	19.2 percentage of participants

SECONDARY outcome

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

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 adjusting for Baseline CGI-S score, center, and treatment.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=144 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=146 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed Week 1 (n=146, 141, 143)	3.35 scores on a scale Standard Error 0.071	3.30 scores on a scale Standard Error 0.070	3.38 scores on a scale Standard Error 0.071
Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed Week 2 (n=148, 143, 146)	2.99 scores on a scale Standard Error 0.083	2.91 scores on a scale Standard Error 0.081	2.92 scores on a scale Standard Error 0.083
Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed Week 4 (n=148, 144, 146)	2.87 scores on a scale Standard Error 0.089	2.75 scores on a scale Standard Error 0.086	2.69 scores on a scale Standard Error 0.088
Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed Week 6 (n=148, 144, 146)	2.68 scores on a scale Standard Error 0.089	2.58 scores on a scale Standard Error 0.087	2.60 scores on a scale Standard Error 0.088
Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed Week 8 (n=148, 144, 146)	2.60 scores on a scale Standard Error 0.095	2.56 scores on a scale Standard Error 0.093	2.51 scores on a scale Standard Error 0.095

SECONDARY outcome

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

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 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 were from an ANCOVA model adjusting for Baseline score, center, and treatment.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=144 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=146 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) Week 8 (n=148, 144, 146)	-1.10 scores on a scale Standard Error 0.090	-1.21 scores on a scale Standard Error 0.088	-1.14 scores on a scale Standard Error 0.090
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) Week 1 (n=146, 140, 143)	-0.40 scores on a scale Standard Error 0.054	-0.47 scores on a scale Standard Error 0.053	-0.37 scores on a scale Standard Error 0.054
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) Week 2 (n=148, 143, 146)	-0.68 scores on a scale Standard Error 0.072	-0.82 scores on a scale Standard Error 0.070	-0.69 scores on a scale Standard Error 0.071
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) Week 4 (n=148, 144, 146)	-0.82 scores on a scale Standard Error 0.081	-1.01 scores on a scale Standard Error 0.079	-0.93 scores on a scale Standard Error 0.081
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) Week 6 (n=148, 144, 146)	-0.93 scores on a scale Standard Error 0.083	-1.14 scores on a scale Standard Error 0.081	-1.03 scores on a scale Standard Error 0.082

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 4 and 8.

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

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 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=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=144 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=146 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales Anxiety Scale at Week 1 (n=147, 142, 143)	-1.64 scores on a scale Standard Deviation 0.266	-2.07 scores on a scale Standard Deviation 0.258	-2.03 scores on a scale Standard Deviation 0.264
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales Anxiety Scale at Week 4 (n=148, 144, 146)	-2.81 scores on a scale Standard Deviation 0.343	-3.66 scores on a scale Standard Deviation 0.333	-3.39 scores on a scale Standard Deviation 0.339
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales Anxiety Scale at Week 8 (n=148, 144, 146)	-3.63 scores on a scale Standard Deviation 0.365	-4.29 scores on a scale Standard Deviation 0.354	-4.20 scores on a scale Standard Deviation 0.361
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales Depression Scale at Week 1 (n=147, 142, 143)	-0.71 scores on a scale Standard Deviation 0.226	-1.35 scores on a scale Standard Deviation 0.220	-1.15 scores on a scale Standard Deviation 0.225
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales Depression Scale at Week 4 (n=148, 144, 146)	-1.66 scores on a scale Standard Deviation 0.272	-2.23 scores on a scale Standard Deviation 0.265	-2.10 scores on a scale Standard Deviation 0.271
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales Depression Scale at Week 8 (n=148, 144, 146)	-1.76 scores on a scale Standard Deviation 0.308	-2.56 scores on a scale Standard Deviation 0.300	-2.21 scores on a scale Standard Deviation 0.306

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set with available data at Baseline; 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=124 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=113 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=109 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) at Week 8	-4.26 scores on a scale Standard Error 0.617	-5.73 scores on a scale Standard Error 0.623	-5.24 scores on a scale Standard Error 0.657

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set with a Baseline SF-36 measurement; 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 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=146 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=141 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=141 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in 36-item Short-form Health Survey (SF-36) Physical functioning subscore	0.46 scores on a scale Standard Error 1.513	2.69 scores on a scale Standard Error 1.478	2.07 scores on a scale Standard Error 1.517
Change From Baseline in 36-item Short-form Health Survey (SF-36) Role - physical subscore	4.44 scores on a scale Standard Error 2.018	8.17 scores on a scale Standard Error 1.972	6.17 scores on a scale Standard Error 2.026
Change From Baseline in 36-item Short-form Health Survey (SF-36) Bodily pain subscore	5.90 scores on a scale Standard Error 1.901	10.67 scores on a scale Standard Error 1.855	8.12 scores on a scale Standard Error 1.905
Change From Baseline in 36-item Short-form Health Survey (SF-36) General health subscore	4.44 scores on a scale Standard Error 1.289	7.01 scores on a scale Standard Error 1.258	5.90 scores on a scale Standard Error 1.292
Change From Baseline in 36-item Short-form Health Survey (SF-36) Vitality subscore	12.35 scores on a scale Standard Error 1.782	15.62 scores on a scale Standard Error 1.740	14.33 scores on a scale Standard Error 1.783
Change From Baseline in 36-item Short-form Health Survey (SF-36) Social functioning subscore	15.35 scores on a scale Standard Error 2.075	18.38 scores on a scale Standard Error 2.025	17.56 scores on a scale Standard Error 2.070
Change From Baseline in 36-item Short-form Health Survey (SF-36) Role-emotional subscore	15.16 scores on a scale Standard Error 2.076	21.72 scores on a scale Standard Error 2.028	16.60 scores on a scale Standard Error 2.081
Change From Baseline in 36-item Short-form Health Survey (SF-36) Mental health subscore	12.93 scores on a scale Standard Error 1.642	17.25 scores on a scale Standard Error 1.608	14.74 scores on a scale Standard Error 1.643

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 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=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=144 Participants Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=146 Participants Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Baseline: Any resource use	32 participants	34 participants	32 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Baseline: Any hospitalization-related services	2 participants	1 participants	1 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Baseline: Hospitalization related to anxiety	1 participants	0 participants	0 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Baseline: Any sick leave	5 participants	13 participants	10 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Baseline: Sick leave related to anxiety	4 participants	8 participants	4 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Week 8: Any resource use	14 participants	23 participants	19 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Week 8: Any hospitalization-related service	3 participants	0 participants	1 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Week 8: Hospitalization related to anxiety	0 participants	0 participants	0 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Week 8: Any sick leave	5 participants	6 participants	8 participants
Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire Week 8: Sick leave related to anxiety	1 participants	4 participants	1 participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 70 other events

Deaths: 0 deaths

Vortioxetine 2.5 mg

Serious events: 2 serious events

Other events: 72 other events

Deaths: 0 deaths

Vortioxetine 10 mg

Serious events: 1 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=153 participants at risk Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 2.5 mg n=151 participants at risk Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks	Vortioxetine 10 mg n=152 participants at risk Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Ear and labyrinth disorders Vertigo positional	0.65% 1/153 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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% 0/151 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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% 0/152 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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 Inguinal hernia	0.00% 0/153 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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.	0.66% 1/151 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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% 0/152 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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.
General disorders Pyrexia	0.00% 0/153 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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.	0.66% 1/151 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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% 0/152 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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	0.00% 0/153 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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% 0/151 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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.	0.66% 1/152 • From the first dose of double-blind study medication through 30 days after permanent discontinuation of double-blind study medication. 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