Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Efavaleukin Alfa in Participants With Systemic Lupus Erythematosus (NCT NCT03451422)

Last Updated: 2023-07-19

Results Overview

A TEAE was defined as any adverse event (AE) starting on or after the first dose of investigational product through to the safety follow-up visit. Any clinically significant changes in physical examinations, vital signs, and clinical laboratory test results were recorded as AEs.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)

Results posted on

2023-07-19

Participant Flow

Participants were enrolled at 10 centers in the United States, France, and Poland from 10 April 2018 to 12 October 2021.

A total of 33 participants were randomized to AMG 592 or placebo in a 5:2 ratio (Cohorts 1, 2, and 3) or in a 1:3 ratio (Cohorts 4 and 5). Of those 33 participants, 2 were re-enrolled and re-randomized to subsequent cohorts upon completion. The total number of informed consent forms signed that led to randomization was 35.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Overall Study STARTED	10	5	5	7	4	4
Overall Study COMPLETED	9	5	2	4	2	2
Overall Study NOT COMPLETED	1	0	3	3	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 2 A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Overall Study Lost to Follow-up	0	0	0	0	1
Overall Study Decision by sponsor	1	1	0	0	0
Overall Study Withdrawal by Subject	0	2	3	2	1

Baseline Characteristics

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Efavaleukin Alfa in Participants With Systemic Lupus Erythematosus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=10 Participants Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=5 Participants A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=5 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=7 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=4 Participants A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 n=4 Participants A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	Total n=35 Participants Total of all reporting groups
Age, Continuous	47.2 years STANDARD_DEVIATION 17.4 • n=5 Participants	44.4 years STANDARD_DEVIATION 13.4 • n=7 Participants	44.4 years STANDARD_DEVIATION 9.2 • n=5 Participants	13.9 years STANDARD_DEVIATION 63.0 • n=4 Participants	16.6 years STANDARD_DEVIATION 57.0 • n=21 Participants	6.6 years STANDARD_DEVIATION 60.0 • n=8 Participants	14.4 years STANDARD_DEVIATION 54.0 • n=8 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=8 Participants	30 Participants n=8 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	5 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=8 Participants	35 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=8 Participants	12 Participants n=8 Participants
Race/Ethnicity, Customized Black or African American and American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants
Race/Ethnicity, Customized White	4 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	21 Participants n=8 Participants
Race/Ethnicity, Customized African and White	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants

PRIMARY outcome

Timeframe: Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)

Population: The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=5 Participants A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=5 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=7 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=4 Participants A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 n=4 Participants A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)	7 Participants	5 Participants	5 Participants	7 Participants	3 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and Days 92, 99, 113 and 127

Population: The Pharmacokinetic (PK) Parameter Analysis Set: All participants who have received AMG 592 and for whom at least one PK parameter could be adequately estimated. Only participants with PK data available for analysis are presented. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=5 Participants A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=7 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=4 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=4 Participants A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Maximum Observed Concentration (Cmax) for AMG 592 First dose (Day 1)	7.92 ng/mL Interval 5.52 to 13.8	13.0 ng/mL Interval 5.01 to 15.8	25.7 ng/mL Interval 9.74 to 43.7	30.7 ng/mL Interval 16.2 to 37.7	44.3 ng/mL Interval 29.6 to 67.9	—
Maximum Observed Concentration (Cmax) for AMG 592 Last dose (Day 85)	9.24 ng/mL Interval 7.05 to 13.7	18.9 ng/mL Interval 14.0 to 23.7	10.0 ng/mL Interval 8.77 to 11.3	56.5 ng/mL Interval 47.1 to 65.8	51.6 ng/mL Interval 25.7 to 77.5	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and Days 92, 99, 113 and 127

Population: The PK Parameter Analysis Set: All participants who have received AMG 592 and for whom at least one PK parameter could be adequately estimated. Only participants with PK data available for analysis are presented. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=5 Participants A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=7 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=4 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=4 Participants A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Time of Cmax (Tmax) for AMG 592 First dose (Day 1)	24.0 hours Interval 12.0 to 74.2	47.6 hours Interval 20.3 to 48.0	24.1 hours Interval 11.9 to 48.0	24.6 hours Interval 24.0 to 27.1	17.8 hours Interval 11.9 to 24.0	—
Time of Cmax (Tmax) for AMG 592 Last dose (Day 85)	25.2 hours Interval 18.8 to 47.5	26.2 hours Interval 23.4 to 28.9	18.0 hours Interval 12.0 to 24.1	24.1 hours Interval 23.5 to 24.7	16.7 hours Interval 12.0 to 21.4	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and Days 92, 99, 113 and 127

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=4 Participants A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=4 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=2 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=3 Participants A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 Last dose (Day 85)	773 hour*ng/mL Interval 444.0 to 1160.0	1120 hour*ng/mL Interval 779.0 to 1460.0	542 hour*ng/mL Interval 347.0 to 736.0	3260 hour*ng/mL Interval 2110.0 to 4420.0	3010 hour*ng/mL Interval 1090.0 to 4930.0	—
Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592 First dose (Day 1)	538 hour*ng/mL Interval 261.0 to 986.0	915 hour*ng/mL Interval 317.0 to 1360.0	1560 hour*ng/mL Interval 971.0 to 2730.0	1960 hour*ng/mL Interval 1960.0 to 1960.0	3770 hour*ng/mL Interval 2020.0 to 5680.0	—

SECONDARY outcome

Timeframe: Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)

Population: The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Only participants who tested positive for anti-AMG 592 antibodies at anytime (pre- or post-dose) were analyzed for presence of anti-IL-2 neutralizing antibodies, as pre-specified. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.

Number of participants who tested positive for developing anti-AMG 592 or anti-IL-2 binding antibodies at 1 or more post-baseline time points, with a negative or no result at baseline, are reported.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=5 Participants A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=5 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=7 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=4 Participants A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 n=4 Participants A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies Binding anti-AMG 592 antibody	0 Participants	3 Participants	3 Participants	6 Participants	2 Participants	4 Participants
Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies Binding anti-IL-2 antibody	—	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)

Number of participants who tested positive for developing anti-AMG 592 or anti-IL-2 neutralizing antibodies at 1 or more post-baseline time points, with a negative or no result at baseline, are reported.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=5 Participants A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=5 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=7 Participants A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=4 Participants A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 n=4 Participants A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies Neutralizing anti-AMG 592 antibody	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies Neutralizing anti-IL-2 antibody	—	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

AMG 592 Cohort 1

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

AMG 592 Cohort 2

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

AMG 592 Cohort 3

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

AMG 592 Cohort 4

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

AMG 592 Cohort 5

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=10 participants at risk Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=5 participants at risk A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=5 participants at risk A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=7 participants at risk A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=4 participants at risk A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 n=4 participants at risk A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Blood and lymphatic system disorders Eosinophilia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Syncope	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.

Other adverse events

Other adverse events
Measure	Placebo n=10 participants at risk Matching placebo was administered by subcutaneous (SC) injection using dosing schedule A or B (A was less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to matching placebo in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	AMG 592 Cohort 1 n=5 participants at risk A low dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 2 n=5 participants at risk A medium dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 3 n=7 participants at risk A medium dose of AMG 592 was administered by SC injection using dosing schedule B (more frequent than schedule A) for a total of 12 weeks.	AMG 592 Cohort 4 n=4 participants at risk A medium/high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks.	AMG 592 Cohort 5 n=4 participants at risk A high dose of AMG 592 was administered by SC injection using dosing schedule A (less frequent than schedule B) for a total of 12 weeks. Two participants who completed Cohort 3 matching placebo dosing were subsequently re-enrolled in the study. One of the participants was randomized to AMG 592 in Cohort 5. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Blood and lymphatic system disorders Eosinophilia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Blood and lymphatic system disorders Lymphadenopathy	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Blood and lymphatic system disorders Neutropenia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Ear and labyrinth disorders Vertigo	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Eye disorders Corneal opacity	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Eye disorders Macular degeneration	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Abdominal pain	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Bowel movement irregularity	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Dry mouth	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	40.0% 2/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Dyspepsia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Dysphagia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Gastrooesophageal reflux disease	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Gingival bleeding	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Nausea	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Reflux gastritis	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Toothache	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Gastrointestinal disorders Vomiting	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Administration site joint erythema	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Administration site joint pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Administration site pruritus	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Administration site reaction	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Administration site swelling	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Application site joint swelling	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Asthenia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	40.0% 2/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Chest pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Cyst	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Fatigue	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	40.0% 2/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Feeling abnormal	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Feeling hot	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Influenza like illness	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site erythema	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	60.0% 3/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	60.0% 3/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	71.4% 5/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	50.0% 2/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	50.0% 2/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site induration	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	50.0% 2/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	50.0% 2/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site inflammation	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site mass	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site pruritus	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	28.6% 2/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	50.0% 2/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	50.0% 2/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site rash	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site reaction	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	40.0% 2/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	60.0% 3/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	28.6% 2/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	50.0% 2/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	75.0% 3/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site swelling	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Injection site warmth	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Malaise	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Non-cardiac chest pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	40.0% 2/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Oedema peripheral	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
General disorders Peripheral swelling	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Hepatobiliary disorders Biliary dyskinesia	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Immune system disorders Hypersensitivity	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Bronchitis	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	28.6% 2/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Cellulitis	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Fungal infection	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	28.6% 2/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Gastroenteritis viral	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Herpes zoster	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Nasopharyngitis	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Oral herpes	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Rhinitis	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Sinusitis	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Upper respiratory tract infection	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	40.0% 2/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Urethritis	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Urinary tract infection	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Infections and infestations Vulvovaginal mycotic infection	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Injury, poisoning and procedural complications Injection related reaction	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Injury, poisoning and procedural complications Spinal column injury	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Investigations Blood pressure decreased	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Investigations Body temperature increased	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	80.0% 4/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Flank pain	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Myalgia intercostal	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Dizziness	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Headache	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Migraine	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Presyncope	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Psychomotor hyperactivity	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Sciatica	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Somnolence	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Nervous system disorders Syncope	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Psychiatric disorders Depression	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Psychiatric disorders Sleep disorder	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Renal and urinary disorders Pollakiuria	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Reproductive system and breast disorders Oedema genital	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	14.3% 1/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Dermatitis acneiform	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Erythema	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	40.0% 2/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	25.0% 1/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Rash	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Rash follicular	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Scab	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Skin discolouration	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Skin and subcutaneous tissue disorders Vitiligo	10.0% 1/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.
Vascular disorders Hypertension	0.00% 0/10 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	20.0% 1/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/5 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/7 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.	0.00% 0/4 • Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up) The Safety Analysis Set: All participants who received at least 1 dose of investigational product. Participants re-enrolled to new cohorts were counted as different participants, as pre-specified.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER