Trial Outcomes & Findings for A Study to Assess the Safety and Efficacy of Etrasimod in Subjects With Moderate-to-Severe Atopic Dermatitis (NCT NCT04162769)

NCT ID: NCT04162769

Last Updated: 2022-11-04

Results Overview

EASI evaluates severity of participant's AD based on severity of AD clinical signs and percent (%) of body surface area (BSA) affected. EASI is a composite scoring assessment of the affected area in 4 specific disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification), which was each assessed on a scale of "0" (absent) through "3" (severe). The EASI Area Score is documented for 4 regions of the body. Region 1: head and neck; Region 2: trunk (including genital area); Region 3: upper limbs; and Region 4: lower limbs (including buttocks), with the area of AD involvement assessed as a percentage by body area and converted to a score of 0 to 6. Total EASI score ranged from 0 to 72; higher score indicated greater severity of AD. Baseline is defined as Day 1 pre-randomization assessments.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 140 participants
• Primary outcome timeframe: Baseline (Day 1) and Week 12
• Results posted on: 2022-11-04

Participant Flow

This was a 2-treatment period study (12-Week Double-Blind Treatment Period and 52-Week Open-label extension [OLE] Period), to evaluate the safety and efficacy of etrasimod monotherapy compared with placebo in participants with moderate-to-severe atopic dermatitis (AD), whose disease was not adequately controlled with topical therapies.

A total of 140 participants were randomized into the 12-week Double-Blind Treatment Period and a total of 95 participants continued into the 52-Week OLE Period.

Participant milestones

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	OLE Period: Etrasimod 2 mg Participants who successfully completed 12 weeks of Double-blind treatment (who received etrasimod 1 mg, etrasimod 2 mg and placebo) continued to the OLE period and received etrasimod 2 mg orally once daily for 52 weeks. Participants who stopped taking study treatment before the end of the Double-blind Treatment period were not eligible to participate in the OLE Period.
Double-blind Treatment (12-Week) STARTED	47	47	46	0
Double-blind Treatment (12-Week) COMPLETED	34	36	37	0
Double-blind Treatment (12-Week) NOT COMPLETED	13	11	9	0
OLE Period (52-Week) STARTED	0	0	0	95
OLE Period (52-Week) COMPLETED	0	0	0	68
OLE Period (52-Week) NOT COMPLETED	0	0	0	27

Reasons for withdrawal

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	OLE Period: Etrasimod 2 mg Participants who successfully completed 12 weeks of Double-blind treatment (who received etrasimod 1 mg, etrasimod 2 mg and placebo) continued to the OLE period and received etrasimod 2 mg orally once daily for 52 weeks. Participants who stopped taking study treatment before the end of the Double-blind Treatment period were not eligible to participate in the OLE Period.
Double-blind Treatment (12-Week) Adverse Event	2	5	0	0
Double-blind Treatment (12-Week) Withdrawal by Subject	4	3	2	0
Double-blind Treatment (12-Week) Physician Decision	1	0	0	0
Double-blind Treatment (12-Week) Lost to Follow-up	5	1	6	0
Double-blind Treatment (12-Week) Protocol deviation	1	1	0	0
Double-blind Treatment (12-Week) Other	0	1	1	0
OLE Period (52-Week) Adverse Event	0	0	0	5
OLE Period (52-Week) Withdrawal by Subject	0	0	0	10
OLE Period (52-Week) Physician Decision	0	0	0	1
OLE Period (52-Week) Lost to Follow-up	0	0	0	9
OLE Period (52-Week) Protocol deviation	0	0	0	2

Baseline Characteristics

A Study to Assess the Safety and Efficacy of Etrasimod in Subjects With Moderate-to-Severe Atopic Dermatitis

Baseline characteristics by cohort

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=47 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=47 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=46 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Total n=140 Participants Total of all reporting groups
Age, Continuous	41.7 Years STANDARD_DEVIATION 13.32 • n=5 Participants	41.8 Years STANDARD_DEVIATION 14.83 • n=7 Participants	44.1 Years STANDARD_DEVIATION 16.16 • n=5 Participants	42.5 Years STANDARD_DEVIATION 14.74 • n=4 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	28 Participants n=7 Participants	27 Participants n=5 Participants	85 Participants n=4 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	55 Participants n=4 Participants
Race/Ethnicity, Customized White	27 Participants n=5 Participants	26 Participants n=7 Participants	31 Participants n=5 Participants	84 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	15 Participants n=5 Participants	18 Participants n=7 Participants	11 Participants n=5 Participants	44 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Full Analysis Set Population

EASI evaluates severity of participant's AD based on severity of AD clinical signs and percent (%) of body surface area (BSA) affected. EASI is a composite scoring assessment of the affected area in 4 specific disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification), which was each assessed on a scale of "0" (absent) through "3" (severe). The EASI Area Score is documented for 4 regions of the body. Region 1: head and neck; Region 2: trunk (including genital area); Region 3: upper limbs; and Region 4: lower limbs (including buttocks), with the area of AD involvement assessed as a percentage by body area and converted to a score of 0 to 6. Total EASI score ranged from 0 to 72; higher score indicated greater severity of AD. Baseline is defined as Day 1 pre-randomization assessments.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=47 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=47 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=46 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Double-blind Treatment Period: Percent Change in Eczema Area and Severity Index (EASI) Score	-58.68 Percent change Standard Error 7.735	-57.18 Percent change Standard Error 7.800	-48.41 Percent change Standard Error 8.378

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Full Analysis Set Population.

EASI-75 is defined as a 75% reduction or greater in EASI score from Baseline to Week 12. Baseline is defined as Day 1 pre-randomization assessments.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=47 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=47 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=46 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Double-blind Treatment Period: Percentage of Participants Achieving EASI-75	27.7 Percentage of participants Interval 15.62 to 42.64	38.3 Percentage of participants Interval 24.51 to 53.62	26.1 Percentage of participants Interval 14.27 to 41.13

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Full Analysis Set Population.

The vIGA scale for AD is a 5-point scale to measure disease severity. The vIGA score was selected using descriptors that best described the overall appearance of skin lesions at a given time point using the following scoring: 0 = clear (no inflammatory signs of AD); 1 = almost clear (barely perceptible erythema and papulation); 2 = mild (slight but definite erythema and papulation); 3 = moderate (clearly perceptible erythema and papulation); and 4 = severe (marked erythema and papulation); Higher score indicated greater severity. Baseline is defined as Day 1 pre-randomization assessments.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=47 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=47 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=46 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Double-blind Treatment Period: Percentage of Participants Achieving a Validated Investigator Global Assessment (vIGA) 0 or 1 Score and a Reduction From Baseline of >= 2 Points	14.9 Percentage of participants Interval 6.2 to 28.31	29.8 Percentage of participants Interval 17.34 to 44.89	13.0 Percentage of participants Interval 4.94 to 26.26

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Full Analysis Set Population. Only those participants with data available at the specified time points were analyzed

Pruritus NRS is an assessment tool that was used to report the intensity of a participant's pruritus (itch). The scale for the pruritus NRS ranged from 0 to 10 with 0 being "no itch" and 10 being "the worst itch imaginable; higher scores indicated greater severity. Baseline is defined as Day 1 pre-randomization assessments.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=27 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=32 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=31 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Double-blind Treatment Period: Percent Change in Weekly Peak Pruritus Numerical Rating Scale (NRS) From an Itch Daily Diary	-38.401 Percent change Standard Error 8.236	-35.044 Percent change Standard Error 7.910	-24.374 Percent change Standard Error 8.492

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Full Analysis Set Population. Only those participants with data available at the specified time points were analyzed.

Pruritus NRS is an assessment tool that was used to report the intensity of a participant's pruritus (itch). The scale for the pruritus NRS ranged from 0 to 10 with 0 being "no itch" and 10 being "the worst itch imaginable; higher scores indicated greater severity. Percentage of participants with improvement (reduction) in peak pruritus NRS >=3 from an itch daily diary is presented. Baseline is defined as Day 1 pre-randomization assessments.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=40 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=40 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=39 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Double-blind Treatment Period: Percentage of Participants With Improvement (Reduction) in Peak Pruritus NRS Greater Than or Equal to (>=)3 From an Itch Daily Diary	45.0 Percentage of participants Interval 29.26 to 61.51	45.0 Percentage of participants Interval 29.26 to 61.51	41.0 Percentage of participants Interval 25.57 to 57.9

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Full Analysis Set Population

EASI-50 is defined as a 50% reduction or greater of EASI from Baseline to Week 12. Percentage of participants achieving EASI-50 is presented. Baseline is defined as Day 1 pre-randomization assessments.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=47 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=47 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=46 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Double-blind Treatment Period: Percentage of Participants Achieving EASI-50	61.7 Percentage of participants Interval 46.38 to 75.49	66.0 Percentage of participants Interval 50.69 to 79.14	52.2 Percentage of participants Interval 36.95 to 67.11

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Full Analysis Set Population

EASI-90 is defined as as a 90% reduction or greater of EASI from Baseline to Week 12. Percentage of participants achieving EASI-90 is presented Baseline is defined as Day 1 pre-randomization assessments.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=47 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=47 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=46 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Double-blind Treatment Period: Percentage of Participants Achieving EASI-90	19.1 Percentage of participants Interval 9.15 to 33.26	14.9 Percentage of participants Interval 6.2 to 28.31	10.9 Percentage of participants Interval 3.62 to 23.57

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Full Analysis Set Population. Only those participants with data available at the specified time points were analyzed.

BSA affected by AD were assessed for each section of the body. The possible highest score for each region was: head and neck (9%), anterior trunk (18%), back (18%), upper limbs (18%), lower limbs (36%), and genitals (1%) and were reported as a percentage of all major body sections combined; higher % BSA indicated greater severity. Baseline is defined as Day 1 pre-randomization assessments

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=36 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=39 Participants Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=39 Participants Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Double-blind Treatment Period: Percent Change in Percent Body Surface Area (BSA)	-34.725 Percent change Standard Error 7.047	-45.153 Percent change Standard Error 6.860	-31.913 Percent change Standard Error 7.012

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 68

Population: Safety Set Population included all randomized participants who received at least 1 dose of study intervention. Only those participants with data available at the specified time points were analyzed.

EASI evaluates severity of participant's AD based on severity of AD clinical signs and percent (%) of body surface area (BSA) affected. EASI is a composite scoring assessment of the affected area in 4 specific disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification), which was each assessed on a scale of "0" (absent) through "3" (severe). The EASI Area Score is documented for 4 regions of the body. Region 1: head and neck; Region 2: trunk (including genital area); Region 3: upper limbs; and Region 4: lower limbs (including buttocks), with the area of AD involvement assessed as a percentage by body area and converted to a score of 0 to 6. Total EASI score ranged from 0 to 72; higher score indicated greater severity of AD. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=68 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
Open-label Extension (OLE) Period: Percent Change in EASI	-45.39 Percent change Standard Deviation 258.796	—	—

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 68

Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.

EASI evaluates severity of participant's AD based on severity of AD clinical signs and percent (%) of body surface area (BSA) affected. EASI is a composite scoring assessment of the affected area in 4 specific disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification), which was each assessed on a scale of "0" (absent) through "3" (severe). The EASI Area Score is documented for 4 regions of the body. Region 1: head and neck; Region 2: trunk (including genital area); Region 3: upper limbs; and Region 4: lower limbs (including buttocks), with the area of AD involvement assessed as a percentage by body area and converted to a score of 0 to 6. Total EASI score ranged from 0 to 72; higher score indicated greater severity of AD. EASI-75 is defined as a >=75% reduction or greater of EASI from Baseline.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=68 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
OLE Period: Number of Participants Achieving a EASI-75 Score	65 Participants	—	—

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 68

Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.

The vIGA scale for AD is a 5-point scale to measure disease severity. The vIGA score was selected using descriptors that best described the overall appearance of skin lesions at a given time point using the following scoring: 0 = clear (no inflammatory signs of AD); 1 = almost clear (barely perceptible erythema and papulation); 2 = mild (slight but definite erythema and papulation); 3 = moderate (clearly perceptible erythema and papulation); and 4 = severe (marked erythema and papulation); Higher score indicated greater severity.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=69 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
OLE Period: Number of Participants Achieving a Validated Investigator Global Assessment (vIGA) 0 or 1 Score and a Reduction From Baseline of ≥ 2 Points	31 Participants	—	—

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 68

Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.

The SCORAD is a validated measure of the extent and severity of AD using 3 components: A = extent or affected BSA, B = severity and C = subjective symptoms. The extent of AD was assessed as percentage of each defined body area and reported as the sum of all areas, with a maximum score of 100%. The severity of 6 specific symptoms was assessed using the following scale: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points, assigned as "B" in the overall SCORAD calculation). Subjective assessment of itch and sleeplessness was recorded for each symptom by the participant or relative on a Visual Analogue Scale, where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum possible score of 20. This parameter is assigned as "C" in the overall SCORAD calculation. The total SCORAD ranged from 0 (no disease) to 103 (severe disease); higher score indicated more severe AD.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=68 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
OLE Period: Percent Change in SCORing Atopic Dermatitis (SCORAD) Total Score	-64.27 Percent change Standard Deviation 69.273	—	—

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 68

Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.

BSA affected by AD were assessed for each section of the body. The possible highest score for each region was: head and neck (9%), anterior trunk (18%), back (18%), upper limbs (18%), lower limbs (36%), and genitals (1%) and were reported as a percentage of all major body sections combined; higher % BSA indicated greater severity. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=68 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
OLE Period: Percent Change in Percent BSA	-68.47 Percent change Standard Deviation 52.083	—	—

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 28

Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.

Pruritus NRS is an assessment tool that was used to report the intensity of a participant's pruritus (itch). The scale for the pruritus NRS ranged from 0 to 10 with 0 being "no itch" and 10 being "the worst itch imaginable; higher scores indicated greater severity. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=56 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
OLE Period: Percent Change in Weekly Peak Pruritus NRS From an Itch Daily Diary	-36.87 Percent change Standard Deviation 45.219	—	—

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 68

Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.

The POEM is a participant-derived validated tool used for monitoring atopic eczema severity. The POEM consisted of 7 questions asking participants to rank how many days over the past 7 days they had experienced specific AD-related symptoms. Each of the 7 questions carried equal weight and was scored from 0 to 4 as follows: No days = 0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; Every day = 4. The scores from the 7 questions were added up to give an overall POEM score as: 0-2 = 'clear/almost clear', 3-7 = 'mild', 8-16 = 'moderate', 17-24 = 'severe', and 25-28 = 'very severe atopic eczema'; higher scores indicated worse atopic eczema severity. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=65 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
OLE Period: Change in Patient-Oriented Eczema Measure (POEM)	-6.3 Scores on a scale Standard Deviation 6.50	—	—

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 68

Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.

The DLQI is a validated 10-item questionnaire designed to measure the impact of skin disease on the Quality of Life (QoL). DLQI is a response to 10 items, which assessed QoL over the past week. For each item, the scale was rated as follows: 0 = "not at all"; 1 = "a little"; 2 = "a lot"; 3 = "very much," with an overall scoring system of 0 to 30; higher scores indicated a poor QoL. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=65 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
OLE Period: Change in Dermatology Life Quality Index (DLQI)	-5.4 Scores on a scale Standard Deviation 6.03	—	—

SECONDARY outcome

Timeframe: Baseline (Week 16) and Week 68

Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.

PGA is an assessment tool that was used by participant to rate the disease and disease severity. Participants rated their overall well-being based on a 5-point Likert scale from poor to excellent. Response choices were: 1- 'Poor', 2- 'Fair', 3- 'Good', 4- 'Very Good,' or 5- 'Excellent'; higher scores indicated better well-being. For the 5-point Likert scale, a positive change from baseline indicates an improvement. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16.

Outcome measures

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=65 Participants Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.
OLE Period: Change in Patient Global Assessment (PGA) of Disease	1.23 Scores on a scale Standard Deviation 1.209	—	—

Adverse Events

Double-blind Treatment Period: Etrasimod 1 Milligrams (mg)

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Double-blind Treatment Period: Etrasimod 2 mg

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Double-blind Treatment Period: Placebo

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

OLE Period: Etrasimod 2 mg

Serious events: 3 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=47 participants at risk Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=47 participants at risk Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=46 participants at risk Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	OLE Period: Etrasimod 2 mg n=95 participants at risk Participants who successfully completed 12 weeks of Double-blind treatment (who received etrasimod 1 mg, etrasimod 2 mg and placebo) continued to the OLE period and received etrasimod 2 mg orally once daily for 52 weeks. Participants who stopped taking study treatment before the end of the Double-blind Treatment period were not eligible to participate in the OLE Period.
Infections and infestations Extradural abscess	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Staphylococcal bacteraemia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Tooth abscess	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Pneumonia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Sepsis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population

Other adverse events

Measure	Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) n=47 participants at risk Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Etrasimod 2 mg n=47 participants at risk Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	Double-blind Treatment Period: Placebo n=46 participants at risk Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study.	OLE Period: Etrasimod 2 mg n=95 participants at risk Participants who successfully completed 12 weeks of Double-blind treatment (who received etrasimod 1 mg, etrasimod 2 mg and placebo) continued to the OLE period and received etrasimod 2 mg orally once daily for 52 weeks. Participants who stopped taking study treatment before the end of the Double-blind Treatment period were not eligible to participate in the OLE Period.
Infections and infestations COVID-19	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Extradural abscess	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Folliculitis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Fungal infection	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Furuncle	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Gastroenteritis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Gastroenteritis viral	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Herpes zoster	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	4.3% 2/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Infection parasitic	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Blood and lymphatic system disorders Coagulopathy	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Blood and lymphatic system disorders Iron deficiency anaemia	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Blood and lymphatic system disorders Leukopenia	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Blood and lymphatic system disorders Lymphopenia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	4.3% 2/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Blood and lymphatic system disorders Thrombocytopenia	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Cardiac disorders Atrioventricular block second degree	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Cardiac disorders Palpitations	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Cardiac disorders Sinus bradycardia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Ear and labyrinth disorders Excessive cerumen production	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Ear and labyrinth disorders Meniere's disease	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Eye disorders Dry eye	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Eye disorders Eyelid cyst	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Eye disorders Vision blurred	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Abdominal distension	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Abdominal pain	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Abdominal pain upper	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Constipation	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	6.4% 3/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Dental caries	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Diarrhoea	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Dyspepsia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Dysphagia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Flatulence	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Nausea	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	6.4% 3/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	4.3% 2/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	4.2% 4/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Tongue discolouration	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Gastrointestinal disorders Vomiting	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
General disorders Chills	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
General disorders Fatigue	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
General disorders Oedema peripheral	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
General disorders Pyrexia	4.3% 2/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Immune system disorders Food allergy	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Arthritis bacterial	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Bacterial vaginosis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Bronchitis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Cellulitis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Infectious pleural effusion	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Influenza	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Nasopharyngitis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Otitis externa	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Paronychia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Pneumonia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Sepsis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Sinusitis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Staphylococcal bacteraemia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Subcutaneous abscess	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Suspected COVID-19	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Tinea infection	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Tooth abscess	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Tooth infection	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Urinary tract infection	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	6.4% 3/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	6.5% 3/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	3.2% 3/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Vaginal infection	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Viral upper respiratory tract infection	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Infections and infestations Vulvovaginal candidiasis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Abdominal injury	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	3.2% 3/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Contusion	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Ear canal injury	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Fall	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Injury	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Joint injury	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Sunburn	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Injury, poisoning and procedural complications Vaccination complication	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Alanine aminotransferase increased	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Blood creatine phosphokinase increased	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Blood creatinine increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Blood potassium increased	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Blood pressure increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Blood triglycerides increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Brain natriuretic peptide increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Coagulation factor increased	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations C-reactive protein increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Full blood count abnormal	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Gamma-glutamyltransferase increased	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Hepatic enzyme increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Lipase increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Lymphocyte count decreased	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	14.9% 7/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	7.4% 7/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Neutrophil count decreased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Procalcitonin increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Red blood cell sedimentation rate increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Red blood cells urine positive	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations SARS-CoV-2 test positive	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	5.3% 5/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Transaminases increased	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations Weight increased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Investigations White blood cell count decreased	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Metabolism and nutrition disorders Decreased appetite	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Metabolism and nutrition disorders Gout	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Metabolism and nutrition disorders Hyperlipidaemia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	3.2% 3/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	4.3% 2/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Musculoskeletal and connective tissue disorders Axillary mass	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	6.4% 3/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Diabetic neuropathy	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Dizziness	4.3% 2/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	6.4% 3/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	4.2% 4/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Essential tremor	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Headache	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	8.7% 4/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	5.3% 5/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Hypoaesthesia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Migraine	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Neuropathy peripheral	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Paraesthesia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Quadriparesis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Somnolence	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Nervous system disorders Taste disorder	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Psychiatric disorders Insomnia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Psychiatric disorders Irritability	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Psychiatric disorders Panic attack	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Psychiatric disorders Suicidal ideation	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Renal and urinary disorders Chromaturia	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Reproductive system and breast disorders Heavy menstrual bleeding	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Respiratory, thoracic and mediastinal disorders Lower respiratory tract congestion	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Skin and subcutaneous tissue disorders Dermal cyst	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	4.3% 2/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	8.7% 4/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	5.3% 5/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Skin and subcutaneous tissue disorders Papule	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	4.3% 2/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.2% 1/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	1.1% 1/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population
Vascular disorders Hypertension	2.1% 1/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/47 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	0.00% 0/46 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population	2.1% 2/95 • All-cause mortality, TEAEs and SAEs were collected for Double-blind Treatment period (12-Week) and for OLE Period (52-Week). Safety Population

Additional Information

Arena CT.gov Administrator

Arena Pharmaceuticals, Inc.

Phone: +1 855-218-9153

Email: ct.gov@arenapharm.com

Results disclosure agreements

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