Trial Outcomes & Findings for Estetrol for the Treatment of Female Sexual Arousal Disorder in Postmenopausal Women (NCT NCT06308614)

Last Updated: 2026-07-06

Results Overview

The Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) is a validated 15-item self-assessment where each item is scored from 0 (never) to 4 (always). Higher scores on this scale, which has a total range of 0-60, indicate greater distress. Item 14 assesses how often the subject has felt concerned by difficulties with sexual arousal during the past 30 days.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

82 participants

Primary outcome timeframe

Baseline, Week 12.

Results posted on

2026-07-06

Participant Flow

Participant milestones

Participant milestones
Measure	Estetrol (E4) 20 mg estetrol monohydrate (E4) -- Active treatment	Placebo Matching Placebo to E4
Overall Study STARTED	41	41
Overall Study COMPLETED	37	34
Overall Study NOT COMPLETED	4	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Estetrol (E4) 20 mg estetrol monohydrate (E4) -- Active treatment	Placebo Matching Placebo to E4
Overall Study Withdrawal by Subject	1	3
Overall Study Adverse Event	1	1
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	0	1
Overall Study Site Closure	0	1

Baseline Characteristics

Only participants with data available at baseline and week 12 are reported.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Estetrol n=37 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=36 Participants Placebo, administered orally once daily for up to 12 weeks.	Total n=73 Participants Total of all reporting groups
Age, Continuous	55.35 years STANDARD_DEVIATION 4.58 • n=37 Participants	56.81 years STANDARD_DEVIATION 5.75 • n=36 Participants	56.07 years STANDARD_DEVIATION 5.21 • n=73 Participants
Sex: Female, Male Female	37 Participants n=37 Participants	36 Participants n=36 Participants	73 Participants n=73 Participants
Sex: Female, Male Male	0 Participants n=37 Participants	0 Participants n=36 Participants	0 Participants n=73 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=37 Participants	1 Participants n=36 Participants	2 Participants n=73 Participants
Race (NIH/OMB) Asian	0 Participants n=37 Participants	0 Participants n=36 Participants	0 Participants n=73 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=37 Participants	0 Participants n=36 Participants	1 Participants n=73 Participants
Race (NIH/OMB) Black or African American	7 Participants n=37 Participants	12 Participants n=36 Participants	19 Participants n=73 Participants
Race (NIH/OMB) White	27 Participants n=37 Participants	23 Participants n=36 Participants	50 Participants n=73 Participants
Race (NIH/OMB) More than one race	1 Participants n=37 Participants	0 Participants n=36 Participants	1 Participants n=73 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	0 Participants n=36 Participants	0 Participants n=73 Participants
Region of Enrollment United States	37 participants n=37 Participants	36 participants n=36 Participants	73 participants n=73 Participants
Body Mass Index (BMI)	30.22 kg/m^2 STANDARD_DEVIATION 4.801 • n=37 Participants	29.41 kg/m^2 STANDARD_DEVIATION 4.607 • n=36 Participants	29.82 kg/m^2 STANDARD_DEVIATION 4.691 • n=73 Participants
FSDS-DAO, Item 14	3.6 score STANDARD_DEVIATION 0.60 • n=37 Participants	3.4 score STANDARD_DEVIATION 0.60 • n=36 Participants	3.5 score STANDARD_DEVIATION 0.60 • n=73 Participants
Sexual Function Questionnaire 28 (SFQ-28) Arousal-Sensation Domain (Questions 6 to 9)	6.8 scores on a scale STANDARD_DEVIATION 2.28 • n=37 Participants	7.1 scores on a scale STANDARD_DEVIATION 2.31 • n=36 Participants	7.0 scores on a scale STANDARD_DEVIATION 2.28 • n=73 Participants
Arousal and Lubrication Assessed by PROMIS-SexFS Questionnaire	6.9 scores on a scale STANDARD_DEVIATION 3.42 • n=37 Participants	7.4 scores on a scale STANDARD_DEVIATION 3.08 • n=36 Participants	7.2 scores on a scale STANDARD_DEVIATION 3.25 • n=73 Participants
FSDS-DAO -- Total Score	45.5 score STANDARD_DEVIATION 9.90 • n=37 Participants	43.0 score STANDARD_DEVIATION 9.95 • n=36 Participants	44.3 score STANDARD_DEVIATION 9.93 • n=73 Participants
Percentage of Satisfying Sexual Events (SSE)	32.1 Percentage of SSE STANDARD_DEVIATION 38.36 • n=36 Participants • Only participants with data available at baseline and week 12 are reported.	31.2 Percentage of SSE STANDARD_DEVIATION 38.44 • n=36 Participants • Only participants with data available at baseline and week 12 are reported.	31.7 Percentage of SSE STANDARD_DEVIATION 38.13 • n=72 Participants • Only participants with data available at baseline and week 12 are reported.
PROMIS-SexFS: Vulvar Discomfort with Sexual Activity - clitoral	2.8 scores on a scale STANDARD_DEVIATION 1.33 • n=37 Participants	3.9 scores on a scale STANDARD_DEVIATION 2.24 • n=36 Participants	3.3 scores on a scale STANDARD_DEVIATION 1.90 • n=73 Participants
Sexual Function Questionnaire 28 (SFQ-28) -- Total Score	62.4 scores on a scale STANDARD_DEVIATION 11.60 • n=37 Participants • Only participants with data available at baseline and week 12 are reported.	66.0 scores on a scale STANDARD_DEVIATION 14.06 • n=35 Participants • Only participants with data available at baseline and week 12 are reported.	64.1 scores on a scale STANDARD_DEVIATION 12.89 • n=72 Participants • Only participants with data available at baseline and week 12 are reported.
PROMIS-SexFS: Interest in Sexual Activity	4.4 scores on a scale STANDARD_DEVIATION 1.34 • n=37 Participants	4.9 scores on a scale STANDARD_DEVIATION 1.46 • n=36 Participants	4.7 scores on a scale STANDARD_DEVIATION 1.42 • n=73 Participants
PROMIS-SexFS: Orgasm- pleasure	3.5 scores on a scale STANDARD_DEVIATION 2.53 • n=37 Participants	3.4 scores on a scale STANDARD_DEVIATION 2.71 • n=36 Participants	3.4 scores on a scale STANDARD_DEVIATION 2.60 • n=73 Participants
PROMIS-SexFS: Orgasm- ability	2.1 scores on a scale STANDARD_DEVIATION 0.81 • n=37 Participants	2.0 scores on a scale STANDARD_DEVIATION 1.10 • n=36 Participants	2.0 scores on a scale STANDARD_DEVIATION 0.96 • n=73 Participants
PROMIS-SexFS: Satisfaction with Sex Life	6.4 scores on a scale STANDARD_DEVIATION 2.36 • n=37 Participants	6.9 scores on a scale STANDARD_DEVIATION 3.19 • n=36 Participants	6.6 scores on a scale STANDARD_DEVIATION 2.79 • n=73 Participants
PROMIS-SexFS: Vaginal Discomfort for Sexual Activity	5.4 scores on a scale STANDARD_DEVIATION 2.31 • n=37 Participants	5.7 scores on a scale STANDARD_DEVIATION 2.12 • n=36 Participants	5.5 scores on a scale STANDARD_DEVIATION 2.21 • n=73 Participants
PROMIS-SexFS: Vulvar Discomfort with Sexual Activity - labial	3.5 scores on a scale STANDARD_DEVIATION 2.02 • n=37 Participants	4.6 scores on a scale STANDARD_DEVIATION 2.44 • n=36 Participants	4.0 scores on a scale STANDARD_DEVIATION 2.29 • n=73 Participants
PROMIS-SexFS: Oral Discomfort	2.8 scores on a scale STANDARD_DEVIATION 1.57 • n=37 Participants	2.8 scores on a scale STANDARD_DEVIATION 1.54 • n=36 Participants	2.8 scores on a scale STANDARD_DEVIATION 1.55 • n=73 Participants
PROMIS-SexFS: Oral Dryness	3.4 scores on a scale STANDARD_DEVIATION 1.83 • n=37 Participants	3.3 scores on a scale STANDARD_DEVIATION 2.14 • n=36 Participants	3.3 scores on a scale STANDARD_DEVIATION 1.98 • n=73 Participants
PROMIS-SexFS: Anal Discomfort	2.4 scores on a scale STANDARD_DEVIATION 1.12 • n=37 Participants	2.2 scores on a scale STANDARD_DEVIATION 0.67 • n=36 Participants	2.3 scores on a scale STANDARD_DEVIATION 0.93 • n=73 Participants
Patient Global Impression of Severity (PGIS)	5.6 scores on a scale STANDARD_DEVIATION 1.06 • n=37 Participants • Only participants with data available at baseline and week 12 are reported.	5.3 scores on a scale STANDARD_DEVIATION 1.44 • n=35 Participants • Only participants with data available at baseline and week 12 are reported.	5.4 scores on a scale STANDARD_DEVIATION 1.27 • n=72 Participants • Only participants with data available at baseline and week 12 are reported.

PRIMARY outcome

Timeframe: Baseline, Week 12.

Population: The FAS is a subset of the Intent-to-Treat (ITT) analysis set and includes all randomized subjects with Baseline and Week 12 efficacy assessments FSDS-DAO Item 14 and SFQ-28 Arousal-Sensation Domain (Questions 6-9). In this analysis set, treatment was assigned based on the treatment to which subjects were randomized, regardless of which treatment they actually received.

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=37 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=36 Participants Placebo, administered orally once daily for up to 12 weeks.
Change From Baseline to Week 12 in Feeling Concerned by Difficulties With Sexual Arousal, Assessed by Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO), Item 14	-1.51 score Interval -1.92 to -1.09	-1.17 score Interval -1.59 to -0.75

PRIMARY outcome

Timeframe: Baseline, Week 12.

The 28-item Sexual Function Questionnaire (SFQ-28) is a validated self-assessment tool to assess female sexual function. It has 8 domains, including domains for desire, arousal (sensation/lubrication/cognitive), orgasm, pain, enjoyment, and partner relationship. Questions are scored on a Likert scale (e.g., 0 to 5 or 1 to 5), where lower scores indicate higher levels of dysfunction. Questions 6, 7, 8, and 9 deal with the domain "Arousal-sensation". Score range for this domain is: 4-20 (=sum of Questions 6-9). Total score range is: 24-141 (=sum of all Questions 1-28).

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=37 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=36 Participants Placebo, administered orally once daily for up to 12 weeks.
Change From Baseline to Week 12 in the Sexual Function Questionnaire 28 (SFQ-28) Arousal-Sensation Domain (Questions 6 to 9)	3.75 scores on a scale Interval 2.34 to 5.17	2.27 scores on a scale Interval 0.88 to 3.66

SECONDARY outcome

Timeframe: Baseline, Week 12.

The PROMIS-SexFS is an instrument to measure self-reported sexual function and satisfaction. In total, 24 questions (out of 26) are rated on a 5-point scale each, so that for each question, the score range may be 1-5 or 0-5 (0=not applicable). Questions (Q) can be grouped by domains; their scores are summed to calculate the domain score. There are 11 domains in total. A higher score indicates a better outcome in the following domains: arousal and lubrication (3Q; 3-15), interest in sexual activity (2Q, score range: 2-10), orgasm-pleasure (2Q; 0-10), orgasm-ability (1Q; 0-5), and satisfaction with sex life (4Q; 3-20). A higher score indicates a worse outcome in the following domains: vaginal discomfort (2Q; 2-10), vulvar discomfort (2Q; 2-10), vulvar dysfunction (2Q; 2-10), oral discomfort (2Q; 2-10), oral dryness (2Q; 2-10), anal discomfort (2Q; 2-10). The 2 remaining questions of the questionnaire are for screening purposes.

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=37 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=36 Participants Placebo, administered orally once daily for up to 12 weeks.
Change From Baseline to Week 12 in Arousal and Lubrication Assessed by Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (SexFS) Measures (PROMIS-SexFS Questionnaire)	3.91 scores on a scale Interval 2.86 to 4.96	2.57 scores on a scale Interval 1.5 to 3.63

SECONDARY outcome

Timeframe: Baseline, Week 12.

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=37 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=36 Participants Placebo, administered orally once daily for up to 12 weeks.
Change From Baseline to Week 12 in Sexual Function Assessed by FSDS-DAO -- Total Score	-16.82 score Interval -21.76 to -11.89	-12.68 score Interval -17.69 to -7.68

SECONDARY outcome

Timeframe: Baseline, Week 12.

A higher number of Satisfying Sexual Events (SSE) indicates an improvement in sexual function. The arousal electronic diary contains a questionnaire to be completed by the subject within 24 hours of a sexual event.

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=36 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=36 Participants Placebo, administered orally once daily for up to 12 weeks.
Change From Baseline to Week 12 in Sexual Function Assessed by Percentage of Satisfying Sexual Events (SSE) -- Captured in Arousal Electronic Diary (Ediary)	36.16 percentage of SSE Interval 26.24 to 46.07	26.37 percentage of SSE Interval 16.45 to 36.28

SECONDARY outcome

Timeframe: Baseline, Week 12.

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=35 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=35 Participants Placebo, administered orally once daily for up to 12 weeks.
Change From Baseline to Week 12 in Sexual Function Assessed by the Sexual Function Questionnaire 28 (SFQ-28) -- Total Score	24.19 scores on a scale Interval 16.52 to 31.87	16.09 scores on a scale Interval 8.42 to 23.77

SECONDARY outcome

Timeframe: Baseline, Week 12.

Refer to Description of Outcome Measure #3.

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=37 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=36 Participants Placebo, administered orally once daily for up to 12 weeks.
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Orgasm- Pleasure	2.60 scores on a scale Interval 1.56 to 3.64	1.88 scores on a scale Interval 0.83 to 2.93
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Orgasm- Ability	1.10 scores on a scale Interval 0.63 to 1.58	0.81 scores on a scale Interval 0.33 to 1.29
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Satisfaction with Sex Life	3.85 scores on a scale Interval 2.28 to 5.42	3.35 scores on a scale Interval 1.75 to 4.94
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Vaginal Discomfort for Sexual Activity	-1.69 scores on a scale Interval -2.32 to -1.06	-1.04 scores on a scale Interval -1.68 to -0.4
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Vulvar Discomfort with Sexual Activity - Labial	-0.82 scores on a scale Interval -1.4 to -0.24	-0.80 scores on a scale Interval -1.38 to -0.21
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Vulvar Discomfort with Sexual Activity - Clitoral	-0.45 scores on a scale Interval -0.91 to 0.01	-0.65 scores on a scale Interval -1.11 to -0.18
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Oral Discomfort	-0.29 scores on a scale Interval -0.64 to 0.07	-0.20 scores on a scale Interval -0.56 to 0.15
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Oral Dryness	-0.24 scores on a scale Interval -0.84 to 0.36	-0.25 scores on a scale Interval -0.86 to 0.36
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Anal Discomfort	-0.10 scores on a scale Interval -0.34 to 0.15	-0.01 scores on a scale Interval -0.26 to 0.23
Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS Interest in Sexual Activity	1.34 scores on a scale Interval 0.71 to 1.97	0.76 scores on a scale Interval 0.12 to 1.41

SECONDARY outcome

Timeframe: Week 12.

Patient Global Impression of Change (PGIC) was used to measure changes in sexual arousal disorder. At Week 12, each enrolled subject was asked to rate their change in sexual arousal on 7-point Likert scale. The results are presented as the number of participants. The grading of responses were from 'No Change' to 'A Great Deal Better', as shown in the results table below.

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=36 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=35 Participants Placebo, administered orally once daily for up to 12 weeks.
Patient Global Impression of Change (PGIC) at Week 12 No change (or condition has got worse)	3 Participants	8 Participants
Patient Global Impression of Change (PGIC) at Week 12 Almost the same, hardly any change at all	6 Participants	12 Participants
Patient Global Impression of Change (PGIC) at Week 12 A little better, but no noticeable change	5 Participants	3 Participants
Patient Global Impression of Change (PGIC) at Week 12 Somewhat better, but the change has not made any real difference	6 Participants	3 Participants
Patient Global Impression of Change (PGIC) at Week 12 Moderately better, and a slight but noticeable change	6 Participants	1 Participants
Patient Global Impression of Change (PGIC) at Week 12 Better, and a definite improvement that has made a real and worthwhile difference	8 Participants	4 Participants
Patient Global Impression of Change (PGIC) at Week 12 A great deal better, and a considerable improvement that has made all the difference	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12.

Patient Global Impression of Severity (PGIS) was used to evaluate the severity of sexual arousal disorder at a given time. The subject is asked to rate the severity of their sexual arousal dysfunction on 7-point Likert scale (1=not present, 2=very mild, 3=mild, 4=moderate, 5=moderately severe, 6=severe, and 7=extremely severe). A lower score indicates an improvement.

Outcome measures

Outcome measures
Measure	Estetrol (E4) n=37 Participants Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=35 Participants Placebo, administered orally once daily for up to 12 weeks.
Change From Baseline to Week 12 in Severity of Sexual Arousal Disorder as Assessed by Patient Global Impression of Severity (PGIS)	-1.62 scores on a scale Interval -2.17 to -1.07	-1.54 scores on a scale Interval -2.11 to -0.98

Adverse Events

Estetrol

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Clinical Trial Transparency

Estetra SRL

Phone: +32 043254451

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Other adverse events
Measure	Estetrol n=41 participants at risk Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, administered orally once daily for up to 12 weeks.	Placebo n=41 participants at risk Placebo, administered orally once daily for up to 12 weeks.
Infections and infestations Upper respiratory tract infection	7.3% 3/41 • Number of events 3 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Infections and infestations Urinary tract infection	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	4.9% 2/41 • Number of events 2 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Infections and infestations Bronchitis	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Infections and infestations COVID-19	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Infections and infestations Cellulitis	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Infections and infestations Gastroenteritis	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Infections and infestations Pneumonia	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Infections and infestations Tooth infection	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Reproductive system and breast disorders Breast tenderness	12.2% 5/41 • Number of events 5 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Reproductive system and breast disorders Nipple pain	9.8% 4/41 • Number of events 4 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Reproductive system and breast disorders Vaginal discharge	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Gastrointestinal disorders Nausea	7.3% 3/41 • Number of events 3 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Gastrointestinal disorders Abdominal pain	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Gastrointestinal disorders Constipation	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Gastrointestinal disorders Diarrhoea	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Gastrointestinal disorders Vomiting	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
General disorders Fatigue	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
General disorders Chest discomfort	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
General disorders Chest pain	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Musculoskeletal and connective tissue disorders Pain in extremity	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Nervous system disorders Headache	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	4.9% 2/41 • Number of events 2 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Ear and labyrinth disorders Vertigo	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Investigations Alanine aminotransferase increased	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Investigations Weight increased	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Psychiatric disorders Depression	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Psychiatric disorders Emotional disorder	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Injury, poisoning and procedural complications Procedural pain	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Metabolism and nutrition disorders Hyperkalaemia	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Renal and urinary disorders Hypertonic bladder	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.
Surgical and medical procedures Removal of internal fixation	2.4% 1/41 • Number of events 1 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.	0.00% 0/41 • Adverse events (AEs) were reported from Day 1 (allocation to treatment) until subject's study participation ended (Week 16 or early withdrawal from the study). Evaluation of AEs (as Treatment-Emergent Adverse Events) was performed using the Safety (SAF) set. This includes all randomized subjects who received at least one dose of Investigational Medicinal Product (IMP). All subjects of the SAF set were analyzed according to the treatment they actually received. The SAF set was used for all safety analyses.