Trial Outcomes & Findings for A Study to Learn How Well the Study Treatment Zabedosertib (BAY1834845) Works and How Safe it is Compared to Placebo in Adult Participants With Moderate-to-severe Atopic Dermatitis (NCT NCT05656911)

Last Updated: 2025-02-18

Results Overview

The endpoint was the composite variable defined as follows: - an EASI 75 response at Week 12 (Day 84), - no stop of study intervention for reasons related to lack of efficacy, - no rescue medication use during the 4 weeks before Day 84 and - no use of systemic atopic dermatitis (AD) treatment. The main estimand was the difference in the proportion of responders between treatment groups in adults with moderate-to-severe atopic dermatitis where use of topical rescue medication from Day 56 (Visit 6) onwards, use of systemic standard of care for AD and discontinuation of treatment due to lack of efficacy are handled as non-response (composite strategy). The estimand was regardless of use of rescue medication before Day 56 (Visit 6), regardless of non-compliance with emollients, and had treatment not been discontinued due to other reasons not related to lack of efficacy. Bayesian analysis according to estimand is presented.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

Week 12 (Day 84)

Results posted on

2025-02-18

Participant Flow

Study was conducted at 22 centers in Europe and US between 21-DEC-2022 (first participant first visit) and 31-JAN-2024 (last participant last visit).

A total of 129 participants were screened in this study. Of those, 52 did not pass screening (44 were screened failures, 1 was physician decision, 6 were subject decision, 1 was other reasons). A total of 77 participants were randomized.

Participant milestones

Participant milestones
Measure	Zabedosertib (BAY1834845) Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Treatment Phase STARTED	52	25
Treatment Phase COMPLETED	36	19
Treatment Phase NOT COMPLETED	16	6
Follow-up Phase STARTED	36	19
Follow-up Phase COMPLETED	35	18
Follow-up Phase NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Zabedosertib (BAY1834845) Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Treatment Phase Physician Decision	2	0
Treatment Phase Lack of Efficacy	6	3
Treatment Phase Subject Decision	4	2
Treatment Phase Other Reasons	1	0
Treatment Phase Adverse Event	3	1
Follow-up Phase Subject Decision	0	1
Follow-up Phase Missing	1	0

Baseline Characteristics

A Study to Learn How Well the Study Treatment Zabedosertib (BAY1834845) Works and How Safe it is Compared to Placebo in Adult Participants With Moderate-to-severe Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zabedosertib (BAY1834845) n=52 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=25 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Total n=77 Participants Total of all reporting groups
Age, Continuous	35.2 years STANDARD_DEVIATION 11.3 • n=5 Participants	32.9 years STANDARD_DEVIATION 10.3 • n=7 Participants	34.4 years STANDARD_DEVIATION 11.0 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	7 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	18 Participants n=7 Participants	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=5 Participants	24 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants	22 Participants n=7 Participants	69 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12 (Day 84)

Population: Per protocol set

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Achievement of 75% Reduction From Baseline in the Eczema Area and Severity Index (EASI 75 Response) at Week 12 (Day 84)	32.3 Percentage (%)	37.4 Percentage (%)

SECONDARY outcome

Timeframe: Baseline and Week 12 (Day 84)

Population: Per protocol set

The EASI is a ClinRO assessing the extent of AD at four body regions by measuring the average severity of four clinical signs at each body region, each on a scale of 0 to 3. The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD. The main estimand was based on the same strategies to address intercurrent events as described above for the primary endpoint. The mean difference between the treatment arms was used as summary measure.

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Percent Change From Baseline in EASI at Week 12 (Day 84)	-44.58 percentage (%) of change Interval -55.96 to -33.19	-55.88 percentage (%) of change Interval -71.91 to -39.85

SECONDARY outcome

Timeframe: Week 12 (Day 84)

Population: Per protocol set

The EASI is a ClinRO assessing the extent of AD at four body regions by measuring the average severity of four clinical signs at each body region, each on a scale of 0 to 3. The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD. EASI 50 corresponds to the achievement of 50% reduction from baseline in EASI. The main estimand was calculated similarly as for EASI 75. Bayesian analysis according to estimand is presented.

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Achievement of EASI 50 Response at Week 12 (Day 84)	52.7 Percentage (%)	55.4 Percentage (%)

SECONDARY outcome

Timeframe: Week 12 (Day 84)

Population: Per protocol set

The EASI is a ClinRO assessing the extent of AD at four body regions by measuring the average severity of four clinical signs at each body region, each on a scale of 0 to 3. The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD. EASI 90 corresponds to the achievement of 90% reduction from baseline in EASI. The main estimand was calculated similarly as for EASI 75. Bayesian analysis according to estimand is presented.

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Achievement of EASI 90 Response at Week 12 (Day 84)	15.6 Percentage (%)	20.4 Percentage (%)

SECONDARY outcome

Timeframe: Week 12 (Day 84)

Population: Per protocol set

vIGA-AD stands for validated Investigator Global Assessment for Atopic Dermatitis. The vIGA-AD is a 1-item static ClinRO using a 5-point scale from 0 (clear) to 4 (severe) based on 4 clinical features of AD lesions: erythema, induration/papulation, lichenification, and oozing/crusting, and takes extent of disease into account. The main estimand was calculated similarly as for EASI 75. Bayesian analysis according to estimand is presented.

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Achievement of a vIGA-AD Response (Score 0 or 1 and ≥ 2 Points Improvement) at Week 12 (Day 84)	15.9 Percentage (%)	28.5 Percentage (%)

SECONDARY outcome

Timeframe: Baseline and Week 12 (Day 84)

Population: Per protocol set

BSA affected by AD was assessed for each section of the body, e.g. using the rule of nines. The possible highest score for each region is: Head and neck - 9%; Anterior trunk - 18%; Back - 18%; Upper limbs - 18%; Lower limbs - 36%; Genitals - 1%. Affected BSA was reported as a percentage of all major body sections combined. The main estimand was based on the same strategies to address intercurrent events as described above for the primary endpoint. The mean difference between the treatment arms was used as summary measure.

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Absolute Change From Baseline in Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 12 (Day 84)	-13.28 percentage of BSA (%) Interval -18.98 to -7.58	-20.34 percentage of BSA (%) Interval -28.6 to -12.07

SECONDARY outcome

Timeframe: Baseline and Week 12 (Day 84)

Population: Per protocol set

NRS stands for numerical rating scale. The Peak Pruritus 0-10 NRS is a single patient-reported item designed to measure peak pruritus (itch), or 'worst' itch, over the previous 24 h based on the following question: 'On a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable", how would you rate your itch at the worst moment during the previous 24 hours?'. ≥ 4 points reduction of the Peak Pruritus 0-10 NRS is considered a clinically relevant within-person response. NRS was assessed on a daily basis and the average over the last 7 days before the visit day was used for analysis. The main estimand was calculated similarly as for EASI 75. Bayesian analysis according to estimand is presented.

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Achievement of a ≥ 4 Point-improvement (Reduction) in the Weekly Average of the Peak Pruritus 0-10 NRS Score From Baseline to Week 12 (Day 84) for Participants With Peak Pruritus 0-10 NRS Score ≥ 4 at Baseline	16.4 Percentage (%)	25.0 Percentage (%)

SECONDARY outcome

Timeframe: Week 12 (Day 84)

Population: Per protocol set

The Peak Pruritus 0-10 NRS is a single patient-reported item designed to measure peak pruritus (itch), or 'worst' itch, over the previous 24 h based on the following question: 'On a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable", how would you rate your itch at the worst moment during the previous 24 hours?'. ≥ 4 points reduction of the Peak Pruritus 0-10 NRS is considered a clinically relevant within-person response. NRS was assessed on a daily basis and the average over the last 7 days before the visit day was used for analysis. The main estimand was based on the same strategies to address intercurrent events as described above for the primary endpoint.

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Absolute Values of Weekly Average of the Peak Pruritus 0-10 Numerical Rating Scale (NRS) Score at Week 12 (Day 84)	5.759 Scores on a scale Standard Deviation 2.218	5.36 Scores on a scale Standard Deviation 2.311

SECONDARY outcome

Timeframe: Baseline and Week 12 (Day 84)

Population: Per protocol set

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=47 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=22 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Percent Change of Weekly Average of the Peak Pruritus 0-10 NRS Score From Baseline at Week 12 (Day 84)	-20.65 percentage of change (%) Interval -29.54 to -11.77	-27.33 percentage of change (%) Interval -40.0 to -14.66

SECONDARY outcome

Timeframe: From first treatment with the study intervention until 7 days after the last intake of study intervention (approximately up to 91 days)

Population: Safety analysis set

Outcome measures

Outcome measures
Measure	Zabedosertib (BAY1834845) n=52 Participants Participants received zabedosertib orally twice daily (BID) for 12 weeks (84 days).	Placebo n=25 Participants Participants received matching placebo to zabedosertib orally twice daily (BID) for 12 weeks (84 days).
Frequency and Severity of Treatment-emergent Adverse Events (TEAEs) Any AE	23 Participants	7 Participants
Frequency and Severity of Treatment-emergent Adverse Events (TEAEs) AE with outcome death	0 Participants	0 Participants
Frequency and Severity of Treatment-emergent Adverse Events (TEAEs) Maximum intensity for any AE -MILD	13 Participants	4 Participants
Frequency and Severity of Treatment-emergent Adverse Events (TEAEs) Maximum intensity for any AE -MODERATE	10 Participants	3 Participants
Frequency and Severity of Treatment-emergent Adverse Events (TEAEs) Any SAE	0 Participants	0 Participants

Adverse Events

Zabedosertib (BAY1834845)

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Therapeutic Area Head

Bayer

Phone: (+) 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The results of this study may be published or presented at scientific meetings by the sponsor. If this is foreseen by the investigator, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	Zabedosertib (BAY1834845) n=52 participants at risk Participants received zabedosertib for up to 12 weeks (84 days)	Placebo n=25 participants at risk Participants received matching placebo to zabedosertib for up to 12 weeks (84 days)
Cardiac disorders Sinus arrhythmia	0.00% 0/52 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Cardiac disorders Tachycardia	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Eye disorders Periorbital oedema	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Gastrointestinal disorders Diarrhoea	3.8% 2/52 • Number of events 2 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Gastrointestinal disorders Tongue oedema	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Gastrointestinal disorders Vomiting	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Gastrointestinal disorders Palatal oedema	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Gastrointestinal disorders Palatal swelling	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
General disorders Pyrexia	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Immune system disorders Hypersensitivity	0.00% 0/52 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Gastroenteritis viral	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Hordeolum	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Nasopharyngitis	7.7% 4/52 • Number of events 4 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Pustule	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Tonsillitis	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Upper respiratory tract infection	0.00% 0/52 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Urethritis	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Viral infection	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Eczema impetiginous	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Infections and infestations Oral herpes	0.00% 0/52 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/52 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Injury, poisoning and procedural complications Limb injury	0.00% 0/52 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Investigations Blood creatine phosphokinase increased	3.8% 2/52 • Number of events 2 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Nervous system disorders Headache	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Nervous system disorders Tremor	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Psychiatric disorders Depression	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Psychiatric disorders Sleep disorder	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Skin and subcutaneous tissue disorders Eczema	3.8% 2/52 • Number of events 3 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Social circumstances Pregnancy of partner	0.00% 0/52 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	4.0% 1/25 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Surgical and medical procedures Gingival graft	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.
Vascular disorders Haematoma	1.9% 1/52 • Number of events 1 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.	0.00% 0/25 • Adverse events tables: from the start of study intervention until 7 days after the last intake (approximately up to 91 days). All-cause mortality is considered after signing informed consent up to the last contact per participant, up to 20 weeks.