Trial Outcomes & Findings for Efficacy and Safety of Vortioxetine (Lu AA21004) for Treatment of Generalized Anxiety Disorder in Adults. (NCT NCT00744627)

Last Updated: 2014-03-03

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 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

301 participants

Primary outcome timeframe

Baseline to Week 8

Results posted on

2014-03-03

Participant Flow

Participants took part in the study at 47 investigative sites in Europe from 23 September 2008 to 07 July 2009.

Participants with a diagnosis of generalized anxiety disorder were enrolled equally in one of two 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 8 weeks.	Vortioxetine 5 mg Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Overall Study STARTED	151	150
Overall Study Treated	150	150
Overall Study COMPLETED	126	128
Overall Study NOT COMPLETED	25	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Overall Study Adverse Event	6	9
Overall Study Lack of Efficacy	7	3
Overall Study Noncompliance	0	1
Overall Study Protocol Deviations	0	2
Overall Study Voluntary Withdrawal	9	6
Overall Study Lost to Follow-up	2	1
Overall Study Other	1	0

Baseline Characteristics

Efficacy and Safety of Vortioxetine (Lu AA21004) for Treatment of Generalized Anxiety Disorder in Adults.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=151 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=150 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.	Total n=301 Participants Total of all reporting groups
Age, Continuous	45.3 years STANDARD_DEVIATION 13.49 • n=99 Participants	45.0 years STANDARD_DEVIATION 14.07 • n=107 Participants	45.1 years STANDARD_DEVIATION 13.76 • n=206 Participants
Age, Customized ≤55 years	112 participants n=99 Participants	111 participants n=107 Participants	223 participants n=206 Participants
Age, Customized >55 years	39 participants n=99 Participants	39 participants n=107 Participants	78 participants n=206 Participants
Sex: Female, Male Female	93 Participants n=99 Participants	103 Participants n=107 Participants	196 Participants n=206 Participants
Sex: Female, Male Male	58 Participants n=99 Participants	47 Participants n=107 Participants	105 Participants n=206 Participants
Race/Ethnicity, Customized Caucasian (White, including Hispanic)	151 participants n=99 Participants	150 participants n=107 Participants	301 participants n=206 Participants
Race/Ethnicity, Customized Black	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Asian	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Native Hawaiian/ Other Pacific Islander	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Race/Ethnicity, Customized Hispanic/Latino	8 participants n=99 Participants	5 participants n=107 Participants	13 participants n=206 Participants
Race/Ethnicity, Customized Non-Hispanic/Non-Latino	143 participants n=99 Participants	145 participants n=107 Participants	288 participants n=206 Participants
Region of Enrollment Estonia	7 participants n=99 Participants	3 participants n=107 Participants	10 participants n=206 Participants
Region of Enrollment Germany	34 participants n=99 Participants	37 participants n=107 Participants	71 participants n=206 Participants
Region of Enrollment Latvia	7 participants n=99 Participants	5 participants n=107 Participants	12 participants n=206 Participants
Region of Enrollment Lithuania	8 participants n=99 Participants	11 participants n=107 Participants	19 participants n=206 Participants
Region of Enrollment Poland	28 participants n=99 Participants	31 participants n=107 Participants	59 participants n=206 Participants
Region of Enrollment Romania	5 participants n=99 Participants	3 participants n=107 Participants	8 participants n=206 Participants
Region of Enrollment Russia	48 participants n=99 Participants	49 participants n=107 Participants	97 participants n=206 Participants
Region of Enrollment Ukraine	14 participants n=99 Participants	11 participants n=107 Participants	25 participants n=206 Participants
Weight	75.76 kg STANDARD_DEVIATION 16.370 • n=99 Participants	72.97 kg STANDARD_DEVIATION 14.981 • n=107 Participants	74.37 kg STANDARD_DEVIATION 15.729 • n=206 Participants
Height	169.56 cm STANDARD_DEVIATION 9.457 • n=99 Participants	168.21 cm STANDARD_DEVIATION 8.653 • n=107 Participants	168.89 cm STANDARD_DEVIATION 9.075 • n=206 Participants
Body Mass Index	26.29 kg/m^2 STANDARD_DEVIATION 4.980 • n=99 Participants	25.69 kg/m^2 STANDARD_DEVIATION 4.419 • n=107 Participants	25.99 kg/m^2 STANDARD_DEVIATION 4.710 • n=206 Participants
Smoking Classification Never Smoked	99 participants n=99 Participants	90 participants n=107 Participants	189 participants n=206 Participants
Smoking Classification Current Smoker	29 participants n=99 Participants	38 participants n=107 Participants	67 participants n=206 Participants
Smoking Classification Ex-smoker	23 participants n=99 Participants	22 participants n=107 Participants	45 participants n=206 Participants
Alcohol Consumption Never	49 participants n=99 Participants	47 participants n=107 Participants	96 participants n=206 Participants
Alcohol Consumption Once monthly or less often	77 participants n=99 Participants	72 participants n=107 Participants	149 participants n=206 Participants
Alcohol Consumption Once a week	15 participants n=99 Participants	18 participants n=107 Participants	33 participants n=206 Participants
Alcohol Consumption 2 to 6 times per week	6 participants n=99 Participants	10 participants n=107 Participants	16 participants n=206 Participants
Alcohol Consumption Daily	4 participants n=99 Participants	3 participants n=107 Participants	7 participants n=206 Participants
Hamilton Anxiety Scale Total Score	26.8 scores on a a scale STANDARD_DEVIATION 3.95 • n=99 Participants	26.3 scores on a a scale STANDARD_DEVIATION 3.92 • n=107 Participants	26.6 scores on a a scale STANDARD_DEVIATION 3.94 • n=206 Participants
Clinical Global Impression - Severity scale score	4.5 scores on a scale STANDARD_DEVIATION 0.67 • n=99 Participants	4.5 scores on a scale STANDARD_DEVIATION 0.70 • n=107 Participants	4.5 scores on a scale STANDARD_DEVIATION 0.69 • n=206 Participants
Hospital Anxiety and Depression - Anxiety subscale	14.4 scores on a scale STANDARD_DEVIATION 3.08 • n=99 Participants	13.8 scores on a scale STANDARD_DEVIATION 2.99 • n=107 Participants	14.1 scores on a scale STANDARD_DEVIATION 3.04 • n=206 Participants
Hospital Anxiety and Depression - Depression subscale	7.5 scores on a scale STANDARD_DEVIATION 4.03 • n=99 Participants	7.6 scores on a scale STANDARD_DEVIATION 3.89 • n=107 Participants	7.5 scores on a scale STANDARD_DEVIATION 3.96 • n=206 Participants
Montgomery Åsberg Depression Rating Scale (MADRS) total score	12.12 scores on a scale STANDARD_DEVIATION 2.375 • n=99 Participants	12.25 scores on a scale STANDARD_DEVIATION 2.219 • n=107 Participants	12.18 scores on a scale STANDARD_DEVIATION 2.296 • n=206 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: The Full Analysis Set 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=126 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=128 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8	-10.49 scores on a scale Standard Error 0.697	-14.30 scores on a scale Standard Error 0.695

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 Hospital Anxiety and Depression (HAD) Anxiety sub-scale consists of 7 items that are assessed on a scale from 0 (no anxiety) to 3 (severe feeling of anxiety). The anxiety subscale determines a state of generalized anxiety including anxious mood, restlessness, anxious thoughts and panic attacks. Scores are summed and range from 0 to 21 (maximal severity). LS means were from a 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 5 mg n=129 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in the Hospital Anxiety and Depression (HAD) Anxiety Subscale at Week 8	-4.20 scores on a scale Standard Error 0.396	-6.49 scores on a scale Standard Error 0.393

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 were from a MMRM with baseline-by-week, center, week and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=128 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Clinical Global Impression Scale-Global Improvement at Week 8	2.66 scores on a scale Standard Error 0.098	2.19 scores on a scale Standard Error 0.098

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 were from a MMRM with Baseline-by-week, center, week and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=109 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=102 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8	-6.14 scores on a scale Standard Error 0.631	-8.10 scores on a scale Standard Error 0.656

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set; Last observation carried forward was used.

Response was defined as participants with a ≥ 50% decrease from Baseline in the Hamilton Anxiety Scale (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 5 mg n=149 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Percentage of Responders in HAM-A Total Score at Week 8	39.9 percentage of participants	61.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: Full analysis set patients with a HAM-A Baseline score ≥25. A mixed model for repeated measurements (MMRM) based on observed cases was used.

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 a MMRM with Baseline-by-week, center, week and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=82 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=82 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25	-10.44 scores on a scale Standard Error 0.895	-15.55 scores on a scale Standard Error 0.904

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: The Full Analysis Set. A mixed model for repeated measurements (MMRM) based on observed cases 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 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 were from a 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 5 mg n=129 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Social Functioning Subscore at Week 8	18.02 scores on a scale Standard Error 1.991	26.80 scores on a scale Standard Error 1.974

SECONDARY outcome

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

Population: The Full Analysis Set. 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-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 a MMRM with Baseline-by-week, center, week and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=149 Participants Vortioxetine 5 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=146, 148)	-2.46 scores on a scale Standard Error 0.272	-2.50 scores on a scale Standard Error 0.270
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed Week 2 (n=147, 144)	-5.05 scores on a scale Standard Error 0.407	-6.21 scores on a scale Standard Error 0.408
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed Week 4 (n=136, 137)	-7.43 scores on a scale Standard Error 0.539	-9.62 scores on a scale Standard Error 0.538
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed Week 6 (n=128, 129)	-9.17 scores on a scale Standard Error 0.609	-11.93 scores on a scale Standard Error 0.608

SECONDARY outcome

Timeframe: Baseline to Weeks 1 and 4

Population: The Full Analysis Set. 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=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=149 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in the Hospital Anxiety and Depression (HAD) Anxiety Subscale at Other Weeks Assessed Week 1 (n=146, 148)	-1.42 scores on a scale Standard Error 0.226	-1.14 scores on a scale Standard Error 0.223
Change From Baseline in the Hospital Anxiety and Depression (HAD) Anxiety Subscale at Other Weeks Assessed Week 4 (n=140, 140)	-3.13 scores on a scale Standard Error 0.298	-4.07 scores on a scale Standard Error 0.296

SECONDARY outcome

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

Population: Full analysis set. 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 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 a MMRM with Baseline-by-week, center, week and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=149 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed Week 2 (n=147, 144)	3.31 scores on a scale Standard Error 0.070	3.10 scores on a scale Standard Error 0.070
Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed Week 1 (n=146, 148)	3.58 scores on a scale Standard Error 0.053	3.67 scores on a scale Standard Error 0.053
Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed Week 4 (n=136, 137)	2.99 scores on a scale Standard Error 0.080	2.66 scores on a scale Standard Error 0.080
Clinical Global Impression Scale-Global Improvement at Other Weeks Assessed Week 6 (n=128, 129)	2.74 scores on a scale Standard Error 0.086	2.43 scores on a scale Standard Error 0.086

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 2 and 4

Population: Full analysis set where Baseline data were available. 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=124 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=120 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Other Weeks Assessed Week 4 (n=112, 107)	-4.35 scores on a scale Standard Error 0.546	-5.13 scores on a scale Standard Error 0.566
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Other Weeks Assessed Week 1 (n=121, 117)	-1.32 scores on a scale Standard Error 0.314	-1.12 scores on a scale Standard Error 0.329
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Other Weeks Assessed Week 2 (n=122, 114)	-2.93 scores on a scale Standard Error 0.440	-3.04 scores on a scale Standard Error 0.459

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=149 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Percentage of Responders in HAM-A Total Score at Other Weeks Assessed Week 6 (n=148, 149)	29.7 percentage of participants	43.6 percentage of participants
Percentage of Responders in HAM-A Total Score at Other Weeks Assessed Week 1 (n=146, 148)	2.7 percentage of participants	2.0 percentage of participants
Percentage of Responders in HAM-A Total Score at Other Weeks Assessed Week 2 (n=148, 149)	12.2 percentage of participants	12.1 percentage of participants
Percentage of Responders in HAM-A Total Score at Other Weeks Assessed Week 4 (n=148, 149)	20.3 percentage of participants	28.9 percentage of participants

SECONDARY outcome

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

Population: Full analysis set patients with a HAM-A Baseline score ≥25. 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-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 a MMRM with Baseline-by-week, center, week and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=96 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 Week 1 (n=100, 95)	-2.64 scores on a scale Standard Error 0.332	-2.62 scores on a scale Standard Error 0.341
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 Week 2 (n=99, 92)	-4.89 scores on a scale Standard Error 0.507	-6.43 scores on a scale Standard Error 0.522
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 Week 4 (n=89, 89)	-7.33 scores on a scale Standard Error 0.694	-10.08 scores on a scale Standard Error 0.702
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 Week 6 (n=83, 83)	-9.02 scores on a scale Standard Error 0.763	-12.90 scores on a scale Standard Error 0.771

SECONDARY outcome

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

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

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 5 mg n=149 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Percentage of Participants in HAM-A Remission at Each Week Assessed Week 1 (n=146, 148)	0 percentage of participants	0 percentage of participants
Percentage of Participants in HAM-A Remission at Each Week Assessed Week 2 (n=148, 149)	2.7 percentage of participants	2.7 percentage of participants
Percentage of Participants in HAM-A Remission at Each Week Assessed Week 4 (n=148, 149)	6.8 percentage of participants	8.7 percentage of participants
Percentage of Participants in HAM-A Remission at Each Week Assessed Week 6 (n=148, 149)	12.2 percentage of participants	16.8 percentage of participants
Percentage of Participants in HAM-A Remission at Each Week Assessed Week 8 (n=148, 149)	17.6 percentage of participants	30.2 percentage of participants

SECONDARY outcome

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

Population: Full analysis set. 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-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 a MMRM with Baseline-by-week, center, week and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=149 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 1 (n=146, 148)	-0.23 scores on a scale Standard Error 0.039	-0.19 scores on a scale Standard Error 0.039
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 2 (n=147, 144)	-0.53 scores on a scale Standard Error 0.060	-0.60 scores on a scale Standard Error 0.060
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 4 (n=136, 137)	-0.87 scores on a scale Standard Error 0.071	-1.04 scores on a scale Standard Error 0.071
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 6 (n=128, 129)	-1.09 scores on a scale Standard Error 0.080	-1.40 scores on a scale Standard Error 0.080
Change From Baseline in Clinical Global Impression Scale-Severity of Illness at Each Week Assessed Week 8 (n=126, 128)	-1.26 scores on a scale Standard Error 0.096	-1.78 scores on a scale Standard Error 0.095

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 4 and 8

Population: The Full Analysis Set. 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 HAD-Depression subscale is completed by the participant and measures depression, focusing on the state of lost interest and diminished pleasure response. The subscale is made up of 7 items that are assessed on a scale from 0 (no depression) to 3 (severe feeling of depression). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. The item scores are summed and the total subscore ranges from 0 to 21 (maximal severity). LS means were from a MMRM with Baseline-by-week, center, week and week-by-treatment as factors in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.	Vortioxetine 5 mg n=149 Participants Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Change From Baseline in the Hospital Anxiety and Depression (HAD) Depression Subscale at Each Week Assessed Week 1 (n=146, 148)	-0.18 scores on a scale Standard Error 0.178	-0.28 scores on a scale Standard Error 0.176
Change From Baseline in the Hospital Anxiety and Depression (HAD) Depression Subscale at Each Week Assessed Week 4 (n=140, 140)	-1.08 scores on a scale Standard Error 0.245	-1.62 scores on a scale Standard Error 0.245
Change From Baseline in the Hospital Anxiety and Depression (HAD) Depression Subscale at Each Week Assessed Week 8 (n=128, 129)	-1.50 scores on a scale Standard Error 0.297	-3.18 scores on a scale Standard Error 0.295

SECONDARY outcome

Timeframe: Baseline to Weeks 2 and 4

Population: The 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.