RELENT-1: Evaluation of the Pharmacokinetics and Safety of BAY3427080 (NT-814) in Post-Menopausal Women With Vasomotor Symptoms

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02865538
• Collaborator: Nerre Therapeutics Ltd. (Industry)
• Enrollment: 76
• Locations: 3
• Arms: 5
• Actual Duration (Months): 7.9
• Patients Per Site: 25.3
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

This is a multi-center, double-blind, randomized, placebo-controlled multiple ascending dose study in post-menopausal women with vasomotor symptoms. Single ascending doses of NT-814 will be investigated in 4 cohorts. Each cohort will comprise of 20 subjects. Subjects will be dosed for 14 days.

Condition or Disease	Intervention/Treatment	Phase
Post-menopausal Vasomotor Symptoms	Drug: BAY3427080; Drug: Placebo (for BAY3427080)	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Pharmacokinetics and Safety of NT-814 in Post-Menopausal Women With Vasomotor Symptoms
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Mar 28, 2017
• Actual Study Completion Date: Mar 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: BAY3427080 Placebo	Drug: Placebo (for BAY3427080)
Experimental: 50mg BAY3427080	Drug: BAY3427080; Other Names: NT-814
Experimental: 100mg BAY3427080	Drug: BAY3427080; Other Names: NT-814
Experimental: 150mg BAY3427080	Drug: BAY3427080; Other Names: NT-814
Experimental: 300mg BAY3427080	Drug: BAY3427080; Other Names: NT-814

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) of BAY3427080 [On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)]

   Cmax is the maximum observed plasma concentration of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.

2. Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of BAY3427080 [On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)]

   Time of occurrence of Cmax.Time to reach maximum plasma concentration of BAY3427080 was presented. Blood samples for Tmax were taken within 30 minutes prior to dose administration.

3. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of BAY3427080 [Day 1 (pre-dose and post-dose (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0 and 24.0 hours)]

   AUC from time zero extrapolated to infinity of BAY3427080 was presented. AUC0-∞ was only estimated following the Day 1 dose.

4. Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-τ) of BAY3427080 [On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)]

   Area under the concentration-time curve (AUC) from time zero to the time of the last quantifiable concentration of BAY3427080 was presented. Blood samples for (AUC0-τ) were taken within 30 minutes prior to dose administration.

5. Terminal Elimination Half-life (t½) of BAY3427080 [On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)]

   Terminal elimination half-life of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.

6. Apparent Clearance (CL/F) of BAY3427080 [On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)]

   Apparent clearance of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.

7. Number of Participants With Clinically Significant Abnormalities Detected Upon Physical Examination. [At day 14]

   A physician or appropriately qualified delegate conducted a full physical examination. Clinically significance was decided by investigator. The findings are presented as abnormal (clinically significant).

8. Number of Participants With Clinically Significant Abnormalities on the 12-lead ECGs [At day 14]

   Reported results are cardiovascular system-examination findings at day 14. Clinically significance was decided by investigator. The findings are presented as abnormal (clinically significant).

9. Number of Participants With Arrhythmias as Assessed by Continuous Holter Monitoring. [Baseline (day -1) and day 14]

   Holter monitors were supplied by iCardiac Technologies. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14 and remained in place until 24-hour assessments were completed.

10. Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Standing) [Baseline and day 14]

    Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.

11. Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Sitting) [Baseline and day 14]

    Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.

12. Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Standing) [Baseline and day 14]

    Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.

13. Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Sitting) [Baseline and day 14]

    Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.

14. Change From Baseline at Day 14 in Vital Signs: Pulse Rate [Baseline and day 14]

    Pulse rate was measured just prior to dosing (approx. 30 mins).

15. Change From Baseline at Day 14 in Vital Signs: Respiratory Rate [Baseline and day 14]

    Respiratory rate was measured just prior to dosing (approx. 30 mins).

16. Change From Baseline at Day 14 in Vital Signs: Oxygen Saturation [Baseline and day 14]

    Oxygen Saturation was measured just prior to dosing (approx. 30 mins).

17. Change From Baseline at Day 14 in Vital Signs: Oral Body Temperature [Baseline and day 14]

    Temperature was measured just prior to dosing (approx. 30 mins).

18. Change From Baseline at Day 14 in Vital Signs: Weight [Baseline and day 14]

    Weight was measured just prior to dosing (approx. 30 mins).

19. Change From Baseline at Day 15 for Laboratory Hormones Results : Adrenocorticotropic Hormone (ADTH) and Estradiol. [Baseline and day 15]

    Blood samples for the assessment of ACTH and Estradiol were collected upon participants admission to the unit.

20. Change From Baseline at Day 15 for Laboratory Hormones Results: Follicle Stimulating Hormone [Baseline and day 15]

    Blood samples for the assessment of Follicle Stimulating were collected upon participants admission to the unit.

21. Change From Baseline at Day 15 for Laboratory Hormones Results : Triiodothyronine Uptake [Baseline and day 15]

    Blood samples for the assessment of Triiodothyronine were collected upon participants admission to the unit.

22. Change From Baseline at Day 15 for Laboratory Hormones Results: Thyrotropin [Baseline and day 15]

    Blood samples for the assessment of Thyrotropin were collected upon participants admission to the unit.

23. Change From Baseline at Day 15 for Laboratory Hormones Results : Cortisol, Testosterone, Thyroxine and Triiodothyronine [Baseline and day 15]

    Blood samples for the assessment of Cortisol, Testosterone, Thyroxine and Triiodothyronine were collected upon participants admission to the unit.

24. Change From Baseline at Day 14 for Clinical Laboratory Parameters LIPIDS : Cholesterol, Triglycerides, HDL Cholesterol and LDL Cholesterol. [Baseline and day 14]

    Blood samples for the assessment of Cholesterol, Triglycerides,high-density lipoprotein (HDL)Cholesterol and low-density lipoprotein (LDL) Cholesterol were collected upon participants admission to the unit.

25. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Immature Granulocytes. [Baseline and day 14]

    Blood samples for the assessment of Neutrophils/Leukocytes, Lymphocytes /Leukocytes, Monocytes/Leukocytes, Eosinophils/Leukocytes, Basophils/Leukocytes and Immature Granulocytes/ Leukocytes were collected upon participants admission to the unit.

26. Change From Baseline at Day 14 for Clinical Laboratory Parameters HEMATOLOGY: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Immature Granulocytes and Platelets. [Baseline and day 14]

    Blood samples for the assessment of Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Immature Granulocytes and Platelets were collected upon participant's admission to the unit.

27. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration [Baseline and day 14]

    Blood samples for the assessment of Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HB)concentration were collected upon participants admission to the unit.

28. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes [Baseline and day 14]

    Blood samples for the assessment of Erythrocytes were collected upon participants admission to the unit.

29. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume. [Baseline and day 14]

    Blood samples for the assessment of Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume were collected upon participants admission to the unit.

30. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Hemoglobin [Baseline and day 14]

    Blood samples for the assessment of Erythrocytes Mean Corpuscular Hemoglobin were collected upon participants admission to the unit.

31. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Distribution Width. [Baseline and day 14]

    Blood samples for the assessment of Erythrocytes Distribution Width were collected upon participants admission to the unit. Erythrocytes distribution width (in percentage) = 1 SD of Erythrocyte volume/MCV x 100%

32. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hematocrit. [Baseline and day 14]

    Blood samples for the assessment of Hematocrit were collected upon participants admission to the unit.

33. Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Protein and Albumin. [Baseline and day 14]

    Blood samples for the assessment of Protein and Albumin were collected upon participants admission to the unit.

34. Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase and Creatine Kinase [Baseline and day 14]

    Blood samples for the assessment of Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase and Creatine Kinase were collected upon participants admission to the unit.

35. Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Urate, Bilirubin and Creatinine. [Baseline and day 14]

    Blood samples for the assessment of Urate, Bilirubin and Creatinine were collected upon participants admission to the unit.

36. Change From Baseline at Day 14 for Clinical Laboratory Parameters CHEMISTRY: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Phosphate, Glucose, Magnesium and Urea Nitrogen. [Baseline and day 14]

    Blood samples for the assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, Phosphate, Glucose, Magnesium and Urea Nitrogen were collected upon participant's admission to the unit.

37. Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate African at Baseline [At Baseline]

    Blood samples for the assessment of Glomerular Filtration Rate African were collected upon participants admission to the unit.

38. Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate Caucasian at Baseline [At Baseline]

    Blood samples for the assessment of Glomerular Filtration Rate Caucasian were collected upon participants admission to the unit.

39. Change From Baseline at Day 14 for COAGULATION: Prothrombin International Normalized Ratio (INR) [Baseline and day 14]

    Blood samples for the assessment of Prothrombin International Normalized Ratio were collected upon participants admission to the unit.

40. Change From Baseline at Day 14 for COAGULATION: Prothrombin Time and Activated Partial Thromboplastin Time [Baseline and day 14]

    Blood samples for the assessment of Prothrombin Time and Activated Partial Thromboplastin Time were collected upon participants admission to the unit.

41. Heart Rate (HR) - Change From Baseline (Day -1) at Day 14 [Baseline (day -1) and day 14]

    Heart rate was measured as part of the 12-lead electrocardiogram. Resting ECG recordings were made.Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.

42. Mean PR Interval - Change From Baseline (Day -1) at Day 14 [Baseline (day -1) and day 14]

    PR Interval was measured as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.

43. Mean QRS Duration - Change From Baseline (Day -1) at Day 14 [Baseline (day -1) and day 14]

    QRS Duration was measured as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.

44. Mean QT Interval - Change From Baseline (Day -1) at Day 14 [Baseline (day -1) and day 14]

    QT Interval was measured as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.

45. Mean QTcF Interval (Fridericia's Correction Formula, QTcF) - Change From Baseline (Day -1) at Day 14 [Baseline (day -1) and day 14]

    Fridericia-corrected QTcF interval was evaluated as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.

46. Mean QTcB Interval (Bazett's Correction Formula, QTcB) - Change From Baseline (Day -1) at Day 14 [Baseline (day -1) and day 14]

    Bazett-corrected QTcB interval was evaluated as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.

47. Nature and Severity of Adverse Events (AEs) up to Day 21 [On or after first drug administration up to end of study (Day 21).]

    An AE was defined as any untoward medical occurrence in a subject or clinical trial subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product. Serious Adverse Event (SAE) is an adverse event that at any dose: Results in death, Is life-threatening (i.e. the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it was more severe), Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect, Is considered to be an important medical event.

48. Withdrawals Due to AEs up to Day 21 [On or after first drug administration up to end of study (Day 21)]

    An AE was defined as any untoward medical occurrence in a subject or clinical trial subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product. Serious Adverse Event (SAE) is an adverse event that at any dose: Results in death, Is life-threatening (i.e. the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it was more severe), Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect, Is considered to be an important medical event.

Secondary Outcome Measures

1. Change in Frequency of Hot Flushes From Baseline (Day -1) at Days 7, 14 as Assessed by Skin Conductance [Baseline (day -1) and days 7, 14]

   Sternal skin conductance monitors (the Bahr MonitorTM) and the associated algorithm software were supplied by Simplex Scientific LLC (Middleton, USA). Participants were instructed to push a button on the skin conductance monitor when they sensed a hot flush when fitted with the monitor and then provide details of the hot flush in the continuous hot flush diary. Sternal skin conductance monitors were fitted on Day -1 (24 hours±1 hour prior to the planned study drug administration on Day 1) and remained in place until after the Day 7 24-hour assessments were completed (on Day 8). Refitted around 30 minutes prior to study drug administration on Day 14 and remained in place until after the 24-hour assessments were completed on Day 15.

2. Change From Baseline (Week -1) at Weeks 1, 2 in Frequency of Moderate to Severe Hot Flushes as Measured by Twice Daily Paper Diary Throughout Study [Baseline (week -1) and Week 1 ,Week 2]

   Hot flush frequency and hot flush severity were obtained using the Hot Flush paper Diary. Subjects documented the number of individual hot flushes experienced and rated the severity of each on a scale of 1 to 3 (mild = 1, moderate = 2, severe = 3). The diaries were completed based on recall twice daily, in the morning and evening.

3. Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Severity of Hot Flushes as Measured by Twice Daily Paper Diary [Baseline (week -1) and weeks 1, Week 2]

   Participants documented the number of individual hot flushes experienced and rated the severity of each on a scale of 1 to 3 (mild = 1, moderate = 2, severe = 3). The diaries were completed based on recall twice daily, in the morning and evening.

4. Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Hot Flushes Severity Score as Measured by Twice Daily Paper Diary. [Baseline (week -1) and week 1 , 2]

   The hot flushes severity score was a composite of the frequency and severity of hot flushes, and was calculated as follows: number of mild hot flushes recorded on Day Y + number of moderate hot flushes recorded on Day Y × 2 + number of severe hot flushes recorded on Day Y × 3. Higher scores mean more severe hot flushes.

5. Change in Frequency From Baseline (Day -1), at Days 7, 14 of Hot Flushes as Measured by Continuous Day Time Diary. [Baseline(day -1) and Day 7, 14]

   Subjects recorded each hot flush and its severity on a scale of 1 to 3 (mild = 1, moderate = 2, severe = 3) in the hot flush paper diary as they occurred during the day and night.

6. Change From Baseline (Week -1) at Weeks 1, 2 in Night-time Awakenings (NTA) Secondary to Hot Flushes as Measured by Paper Diary [Baseline (week-1) and weeks 1 , 2]

   The number of NTAs secondary to hot flushes was the sum of the number of moderate and severe night-time hot flushes recorded the following morning (twice-daily hot flush diary) or recorded contemporaneously on the continuous diary.

7. Change From Baseline (Day-1) to Day 1 and Day 7 in Luteinizing Hormone (AUC0-8) [baseline (day-1) to day 1 and day 7, pre-dose and post-dose (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0 and 24.0 hours)]

   Change in Luteinizing Hormone(LH) AUC from time zero to 8 hours. Pre-dose samples for LH were taken within 30 minutes prior to dose administration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Post-menopausal female subjects experiencing frequent moderate to severe hot flashes.Menopause will be defined as:

• 12 months of spontaneous amenorrhea;

• OR at least 6 weeks' post-surgical bilateral oophorectomy with or without hysterectomy.

Exclusion Criteria:

• BMI > 35kg/m2.

• Any active comorbid disease, ECG or laboratory result deemed by the investigator to be clinically significant and which could impact safety during study conduct or that could interfere with the study evaluation, procedures or completion.

• Use of prohibited medications defined in the protocol.

• Inability or unwillingness to comply with study procedures or requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Avail Clinical Research	DeLand	Florida	United States	32720
2	QPS/MRA (Miami Clinical Research)	Miami	Florida	United States	33143
3	ICON Clinical Research Unit	San Antonio	Texas	United States	78209

Sponsors and Collaborators

• Bayer
• Nerre Therapeutics Ltd.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 13, 2016
• Statistical Analysis Plan - May 5, 2017

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02865538
• Other Study ID Numbers: 21681
• First Posted: Aug 12, 2016
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bayer: Hot flashes; Post-menopausal

Study Results

Participant Flow

Recruitment Details	The study was conducted between 01 August 2016 (first subject, screening visit) and 28 March 2017 (last subject, last visit).
Pre-assignment Detail	Overall 316 subjects were screened, of them 240 were screening failure. 76 subjects were randomized and assigned to treatment. 18 subjects were randomized to placebo and 58 subjects to BAY3427080 (NT-814) arms. 2 subjects discontinued the study .

Arm/Group Title	Placebo Comparator	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg of BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	300 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.
Period Title: Overall Study
STARTED	18	15	15	15	13
COMPLETED	17	15	14	15	13
NOT COMPLETED	1	0	1	0	0

Baseline Characteristics

Arm/Group Title	Placebo Comparator	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg of BAY3427080	Total
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	300 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	Total of all reporting groups
Overall Participants	18	15	15	15	13	76
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.2 (4.08)	55.9 (5.57)	55.3 (5.43)	56.7 (4.37)	53.8 (3.88)	55.4 (4.67)
Sex: Female, Male (Count of Participants)
Female	18 100%	15 100%	15 100%	15 100%	13 100%	76 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 72.2%	10 66.7%	8 53.3%	10 66.7%	9 69.2%	50 65.8%
Not Hispanic or Latino	5 27.8%	5 33.3%	7 46.7%	5 33.3%	4 30.8%	26 34.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 11.1%	4 26.7%	4 26.7%	2 13.3%	2 15.4%	14 18.4%
White	16 88.9%	11 73.3%	11 73.3%	13 86.7%	11 84.6%	62 81.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	73.25 (10.11)	70.85 (11.82)	73.47 (14.93)	72.10 (7.10)	72.73 (12.05)	72.48 (11.20)

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of BAY3427080
Description	Cmax is the maximum observed plasma concentration of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.
Time Frame	On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)

Outcome Measure Data

Analysis Population Description

Participants who received placebo were not included in the PK population.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	0	15	15	15	13
Day 1	502.62 (90.19)	731.69 (110.58)	911.48 (148.28)	1576.01 (90.70)
Day 7	548.60 (57.47)	809.48 (116.58)	1173.50 (95.14)	2045.61 (152.87)
Day 14	522.36 (87.88)	841.42 (107.16)	1188.19 (131.20)	2851.83 (116.53)

2. Primary Outcome

Title	Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of BAY3427080
Description	Time of occurrence of Cmax.Time to reach maximum plasma concentration of BAY3427080 was presented. Blood samples for Tmax were taken within 30 minutes prior to dose administration.
Time Frame	On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)

Outcome Measure Data

Analysis Population Description

Participants who received placebo were not included in the PK population.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	0	15	15	15	13
Day 1	1.360 (40.01)	1.320 (38.79)	1.521 (41.95)	1.471 (63.05)
Day 7	1.432 (39.25)	1.623 (43.19)	1.536 (40.08)	1.754 (56.18)
Day 14	1.265 (46.32)	1.445 (56.71)	1.296 (23.35)	1.342 (33.46)

3. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of BAY3427080
Description	AUC from time zero extrapolated to infinity of BAY3427080 was presented. AUC0-∞ was only estimated following the Day 1 dose.
Time Frame	Day 1 (pre-dose and post-dose (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0 and 24.0 hours)

Outcome Measure Data

Analysis Population Description

Participants in PK population with available data are reported. Participants who received placebo were not included in the PK population.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	0	7	2	3	5
Geometric Mean (Geometric Coefficient of Variation) [hr*ng/mL]	2018.68 (38.43)	1545.58 (3.49)	1151.87 (66.73)	6249.52 (101.01)

4. Primary Outcome

Title	Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-τ) of BAY3427080
Description	Area under the concentration-time curve (AUC) from time zero to the time of the last quantifiable concentration of BAY3427080 was presented. Blood samples for (AUC0-τ) were taken within 30 minutes prior to dose administration.
Time Frame	On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)

Outcome Measure Data

Analysis Population Description

Participants who received placebo were not included in the PK population.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	0	15	15	15	13
Day 1	1400.167 (67.87)	2341.882 (71.19)	3012.793 (97.74)	6527.569 (70.50)
Day 7	2506.97 (48.05)	4472.76 (63.83)	6202.894 (43.92)	12859.660 (85.47)
Day 14	2341.55 (64.73)	3542.41 (86.34)	5163.500 (88.71)	14822.860 (99.68)

5. Primary Outcome

Title	Terminal Elimination Half-life (t½) of BAY3427080
Description	Terminal elimination half-life of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.
Time Frame	On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)

Outcome Measure Data

Analysis Population Description

Participants in PK population with available data are reported. Participants who received placebo were not included in the PK population.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	0	7	2	8	11
Day 1	2.409 (34.15)	1.903 (11.98)	3.965 (45.94)	3.142 (18.92)
Day 7	2.443 (9.33)	3.303 (21.20)	3.482 (22.57)	2.271
Day 14	2.698 (21.64)	2.042	21.593 (24.58)	20.427 (22.85)

6. Primary Outcome

Title	Apparent Clearance (CL/F) of BAY3427080
Description	Apparent clearance of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.
Time Frame	On Day 1, Day 7 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0 hours) and on Day 14 (Pre-dose; 0.5; 1.0; 1.5; 2.0; 2.5; 3.0; 4.0; 5.0; 6.0; 8.0; 12.0; 24.0, 48.0, 72.0 hours)

Outcome Measure Data

Analysis Population Description

Participants who received placebo were not included in the PK population.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	0	15	15	15	13
Day 1	24.769 (38.43)	64.700 (3.49)	130.223 (66.73)	48.004 (101.01)
Day 7	19.944 (48.05)	22.358 (63.83)	24.182 (43.92)	23.329 (85.47)
Day 14	21.353 (64.73)	28.229 (86.34)	29.050 (88.71)	20.239 (99.68)

7. Primary Outcome

Title	Number of Participants With Clinically Significant Abnormalities Detected Upon Physical Examination.
Description	A physician or appropriately qualified delegate conducted a full physical examination. Clinically significance was decided by investigator. The findings are presented as abnormal (clinically significant).
Time Frame	At day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Number [Participants]	1 5.6%	0 0%	2 13.3%	1 6.7%	2 15.4%

8. Primary Outcome

Title	Number of Participants With Clinically Significant Abnormalities on the 12-lead ECGs
Description	Reported results are cardiovascular system-examination findings at day 14. Clinically significance was decided by investigator. The findings are presented as abnormal (clinically significant).
Time Frame	At day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Number [Participants]	0 0%	0 0%	1 6.7%	0 0%	0 0%

9. Primary Outcome

Title	Number of Participants With Arrhythmias as Assessed by Continuous Holter Monitoring.
Description	Holter monitors were supplied by iCardiac Technologies. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14 and remained in place until 24-hour assessments were completed.
Time Frame	Baseline (day -1) and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Average Hourly Daytime Heart Rate < 50 bpm (daytime defined as 7 am-10 pm)(Day-1)	0 0%	0 0%	1 6.7%	0 0%	0 0%
Frequent Supraventricular Premature Beats (APBs) (>100/24hrs) (Day-1)	2 11.1%	1 6.7%	3 20%	0 0%	0 0%
Frequent Ventricular Ectopic Beats (VEs) (> 200/24hrs) (Day-1)	1 5.6%	4 26.7%	1 6.7%	0 0%	2 15.4%
Other arrhythmias (Day-1)	17 94.4%	13 86.7%	15 100%	15 100%	12 92.3%
Second Degree AV Block - Type I (Day-1)	1 5.6%	0 0%	0 0%	0 0%	0 0%
Sinus Bradycardia (HR < 40 bpm)(Day-1)	0 0%	0 0%	1 6.7%	0 0%	0 0%
SupraVentricular Tachycardia (lasting > 10 beats) (Day-1)	4 22.2%	5 33.3%	4 26.7%	2 13.3%	1 7.7%
At least three monomorphic beats in a row (Day 14)	0 0%	0 0%	0 0%	1 6.7%	0 0%
Average Hourly Daytime Heart Rate < 50 bpm (daytime defined as 7 am-10 pm) (Day 14)	0 0%	0 0%	0 0%	0 0%	1 7.7%
Frequent Supraventricular Premature Beats (APBs) (>100/24hrs) (Day 14)	1 5.6%	0 0%	0 0%	0 0%	0 0%
Frequent Ventricular Ectopic Beats (VEs) (> 200/24hrs) (Day 14)	1 5.6%	4 26.7%	0 0%	0 0%	1 7.7%
Other arrhythmias (Day 14)	18 100%	14 93.3%	13 86.7%	15 100%	13 100%
Presence of NSVT (Non-Sustained Ventricular Tachycardia) episodes (Day 14)	0 0%	0 0%	0 0%	1 6.7%	0 0%
Second Degree AV Block - Type I (Day 14)	2 11.1%	0 0%	0 0%	0 0%	0 0%
Second Degree AV Block - Type II(Day 14)	1 5.6%	0 0%	0 0%	1 6.7%	0 0%
Sinus Bradycardia (HR < 40 bpm)	0 0%	0 0%	0 0%	1 6.7%	0 0%
SupraVentricular Tachycardia (lasting > 10 beats (Day 14)	3 16.7%	3 20%	1 6.7%	1 6.7%	1 7.7%

10. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Standing)
Description	Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	80.11 (4.702)	76.07 (5.257)	77.67 (11.462)	78.93 (6.147)	77.92 (9.768)
Day 14 Change from Baseline	1.11 (9.579)	2.53 (5.540)	-0.07 (12.137)	0.93 (7.216)	1.62 (9.097)

11. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Sitting)
Description	Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	77.72 (6.542)	74.27 (6.239)	77.20 (10.705)	74.80 (6.774)	74.15 (8.245)
Day 14 Change from Baseline	0.11 (9.292)	-0.53 (6.906)	-0.79 (9.736)	2.73 (9.384)	1.77 (6.366)

12. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Standing)
Description	Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	117.83 (10.733)	114.60 (8.675)	121.33 (17.867)	118.87 (11.513)	114.77 (15.095)
Day 14 Change from Baseline	5.11 (11.483)	3.80 (13.311)	-4.43 (18.744)	0.33 (12.234)	5.62 (16.536)

13. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Sitting)
Description	Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	116.39 (11.304)	113.80 (9.405)	119.07 (15.931)	117.20 (10.638)	114.15 (14.288)
Day 14 Change from Baseline	4.17 (11.868)	0.20 (10.359)	-2.79 (16.470)	2.47 (16.890)	5.62 (12.672)

14. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Pulse Rate
Description	Pulse rate was measured just prior to dosing (approx. 30 mins).
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	69.89 (8.629)	66.00 (6.358)	69.20 (9.966)	68.40 (4.611)	72.62 (7.136)
Day 14 Change from Baseline	1.06 (8.271)	-2.00 (8.027)	0.14 (7.263)	0.27 (8.388)	-11.00 (9.618)

15. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Respiratory Rate
Description	Respiratory rate was measured just prior to dosing (approx. 30 mins).
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	15.39 (1.378)	15.47 (1.727)	15.73 (1.624)	15.60 (1.502)	15.85 (1.573)
Day 14 Change from Baseline	-0.11 (2.220)	-0.40 (2.197)	0.07 (1.940)	-0.43 (2.065)	-1.33 (1.923)

16. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Oxygen Saturation
Description	Oxygen Saturation was measured just prior to dosing (approx. 30 mins).
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	98.50 (1.098)	98.40 (1.404)	97.87 (1.727)	97.67 (1.496)	97.31 (1.251)
Day 14 Change from Baseline	-0.61 (1.539)	-0.73 (1.486)	0.29 (2.091)	0.20 (1.424)	0.38 (1.193)

17. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Oral Body Temperature
Description	Temperature was measured just prior to dosing (approx. 30 mins).
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	36.77 (0.190)	36.65 (0.155)	36.79 (0.162)	36.71 (0.168)	36.77 (0.361)
Day 14 Change from Baseline	-0.04 (0.243)	0.06 (0.172)	-0.09 (0.264)	-0.01 (0.239)	-0.05 (0.458)

18. Primary Outcome

Title	Change From Baseline at Day 14 in Vital Signs: Weight
Description	Weight was measured just prior to dosing (approx. 30 mins).
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	73.25 (10.115)	70.85 (11.821)	73.47 (14.934)	72.10 (7.104)	72.73 (12.047)
Day 14 Change from Baseline	0.36 (1.034)	0.51 (0.983)	0.24 (0.916)	0.15 (0.926)	0.01 (0.704)

19. Primary Outcome

Title	Change From Baseline at Day 15 for Laboratory Hormones Results : Adrenocorticotropic Hormone (ADTH) and Estradiol.
Description	Blood samples for the assessment of ACTH and Estradiol were collected upon participants admission to the unit.
Time Frame	Baseline and day 15

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (ADTH)	5.34 (3.402)	4.17 (1.991)	3.87 (2.361)	3.55 (2.360)	3.27 (2.011)
Day 15 Change from Baseline (ADTH)	-0.49 (3.333)	-0.68 (2.035)	0.84 (1.914)	1.04 (3.059)	1.67 (3.059)
Baseline (Estradiol)	57.33 (43.236)	59.49 (40.129)	35.02 (25.556)	43.83 (31.270)	62.42 (42.589)
Day 15 Change from Baseline (Estradiol)	22.43 (141.618)	13.21 (80.704)	0.53 (3.172)	1.96 (12.394)	-9.02 (87.480)

20. Primary Outcome

Title	Change From Baseline at Day 15 for Laboratory Hormones Results: Follicle Stimulating Hormone
Description	Blood samples for the assessment of Follicle Stimulating were collected upon participants admission to the unit.
Time Frame	Baseline and day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	76.01 (23.122)	100.87 (36.813)	77.78 (20.132)	88.77 (42.251)	70.59 (17.046)
Day 15 Change from Baseline	5.98 (13.072)	-2.29 (20.948)	4.09 (8.353)	6.73 (6.904)	8.92 (13.409)

21. Primary Outcome

Title	Change From Baseline at Day 15 for Laboratory Hormones Results : Triiodothyronine Uptake
Description	Blood samples for the assessment of Triiodothyronine were collected upon participants admission to the unit.
Time Frame	Baseline and day 15

Outcome Measure Data

Analysis Population Description

Participants in PK analysis set with evaluable data for this outcome measure presented.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	0
Baseline	32.300 (3.5623)	30.800 (2.4712)	30.838 (1.7968)	30.671 (1.3060)
Day 15 Change from Baseline	-0.720 (0.7662)	-0.700 (0.2944)	0.143 (0.7115)	0.443 (1.0130)

22. Primary Outcome

Title	Change From Baseline at Day 15 for Laboratory Hormones Results: Thyrotropin
Description	Blood samples for the assessment of Thyrotropin were collected upon participants admission to the unit.
Time Frame	Baseline and day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	2.658 (1.7584)	1.800 (0.9830)	2.451 (1.4811)	2.785 (1.1449)	2.330 (1.2658)
Day 15 Change from Baseline	-0.959 (1.3501)	-0.571 (0.8148)	-0.648 (0.5903)	-0.823 (1.0604)	-0.616 (1.1375)

23. Primary Outcome

Title	Change From Baseline at Day 15 for Laboratory Hormones Results : Cortisol, Testosterone, Thyroxine and Triiodothyronine
Description	Blood samples for the assessment of Cortisol, Testosterone, Thyroxine and Triiodothyronine were collected upon participants admission to the unit.
Time Frame	Baseline and day 15

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Cortisol)	348.60 (156.496)	337.16 (177.507)	345.91 (173.302)	251.66 (144.743)	230.42 (74.560)
Day 15 Change from Baseline (Cortisol)	15.94 (193.564)	-23.32 (172.685)	68.05 (170.121)	92.02 (159.464)	127.20 (208.452)
Baseline (Testosterone)	0.744 (0.3850)	0.666 (0.6230)	0.517 (0.2317)	0.433 (0.2961)	0.611 (0.4271)
Day 15 Change from Baseline (Testosterone)	0.057 (0.3567)	0.024 (0.2578)	0.696 (0.3367)	0.480 (0.4589)	0.524 (0.2905)
Baseline(Thyroxine)	95.44 (14.576)	95.66 (15.203)	96.11 (14.645)	86.41 (16.116)	94.16 (22.180)
Day 15 Change from Baseline(Thyroxine)	-3.78 (14.771)	-1.28 (8.127)	-10.67 (26.324)	6.53 (9.546)	0.88 (13.720)
Baseline(Triiodothyronine)	1.865 (0.14131)	2.060 (0.3174)	1.980 (0.2916)	1.776 (0.4510)	2.163 (0.6008)
Day 15 Change from Baseline (Triiodothyronine)	-0.190 (0.3171)	-0.141 (0.2742)	-0.407 (0.2180)	-0.148 (0.1883)	-0.416 (0.5359)

24. Primary Outcome

Title	Change From Baseline at Day 14 for Clinical Laboratory Parameters LIPIDS : Cholesterol, Triglycerides, HDL Cholesterol and LDL Cholesterol.
Description	Blood samples for the assessment of Cholesterol, Triglycerides,high-density lipoprotein (HDL)Cholesterol and low-density lipoprotein (LDL) Cholesterol were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Cholesterol)	5.434 (1.0223)	5.471 (0.6592)	5.391 (0.7346)	5.804 (0.6462)	5.393 (0.9008)
Day 14 Change from Baseline (Cholesterol)	0.088 (0.8629)	-0.061 (0.4761)	-0.205 (0.8981)	-0.185 (0.6386)	-0.321 (0.6790)
Baseline (Triglycerides)	1.163 (0.5796)	1.185 (0.5036)	1.131 (0.5889)	1.329 (0.6245)	1.353 (0.5540)
Day 14 Change from Baseline (Triglycerides)	0.048 (0.4936)	-0.071 (0.4725)	-0.116 (0.5247)	-0.029 (0.4178)	-0.172 (0.5633)
Baseline(HDL Cholesterol)	1.717 (0.4525)	1.879 (0.4052)	1.7444 (0.6563)	1.768 (0.4716)	1.449 (0.2752)
Day 14 Change from Baseline( HDL Cholesterol)	-0.167 (0.2824)	-0.219 (0.2015)	-0.056 (0.2559)	-0.147 (0.1546)	-0.158 (0.3132)
Baseline( LDL Cholesterol)	3.226 (1.0485)	3.125 (0.8436)	3.172 (0.7654)	3.625 (0.7188)	3.552 (1.1088)
Day 14 Change from Baseline ( LDL Cholesterol)	-0.013 (0.3926)	0.184 (0.2958)	-0.119 (0.6747)	-0.038 (0.6490)	-0.053 (0.5944)

25. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Immature Granulocytes.
Description	Blood samples for the assessment of Neutrophils/Leukocytes, Lymphocytes /Leukocytes, Monocytes/Leukocytes, Eosinophils/Leukocytes, Basophils/Leukocytes and Immature Granulocytes/ Leukocytes were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Neutrophils/ Leukocytes)	56.53 (7.700)	53.31 (4.994)	55.65 (8.318)	54.78 (8.610)	50.92 (10.316)
Day 14 Change from Baseline (Neutrophils/ Leukocytes)	-0.29 (7.788)	2.41 (6.119)	-0.50 (5.047)	-0.98 (7.116)	-2.69 (10.614)
Baseline (Lymphocytes/ Leukocytes)	32.40 (7.098)	35.57 (5.439)	33.33 (8.024)	34.33 (7.444)	36.78 (10.446)
Day 14 Change from Baseline(Lymphocytes / Leukocytes)	0.18 (5.791)	-2.46 (5.667)	-0.11 (4.763)	0.59 (5.835)	2.75 (10.926)
Baseline ( Monocytes / Leukocytes )	7.58 (1.592)	7.47 (1.379)	7.62 (1.591)	7.71 (1.762)	8.62 (3.276)
Day 14 Change from Baseline( Monocytes/ Leukocytes)	0.22 (1.947)	-0.15 (1.751)	0.65 (1.291)	0.05 (2.758)	0.22 (3.850)
Baseline ( Eosinophils/ Leukocytes)	2.83 (2.433)	3.04 (3.352)	2.64 (1.422)	2.61 (1.170)	3.05 (1.979)
Day 14 Change from Baseline(Eosinophils/ Leukocytes)	0.02 (1.316)	0.29 (0.961)	0.06 (0.794)	0.33 (0.538)	-0.24 (1.189)
Baseline(Basophils/ Leukocytes)	0.61 (0.263)	0.55 (0.177)	0.66 (0.295)	0.51 (0.223)	0.56 (0.373)
Day 14 Change from Baseline (Basophils/ Leukocytes)	-0.13 (0.181)	-0.07 (0.111)	-0.14 (0.122)	0.01 (0.209)	-0.05 (0.307)
Baseline( Immature Granulocytes/ Leukocytes)	0.15 (0.084)	0.25 (0.100)	0.20 (0.151)	0.13 (0.111)	0.15 (0.084)
Day 14 Change from Baseline( Immature Granulocytes/ Leukocytes)	0.03 (0.082)	-0.05 (0.100)	0.09 (0.157)	0.00 (0.183)	0.03 (0.137)

26. Primary Outcome

Title	Change From Baseline at Day 14 for Clinical Laboratory Parameters HEMATOLOGY: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Immature Granulocytes and Platelets.
Description	Blood samples for the assessment of Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Immature Granulocytes and Platelets were collected upon participant's admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline( Leukocytes)	6.73 (1.372)	6.54 (1.613)	6.75 (1.245)	6.78 (1.307)	6.60 (1.896)
Day 14 Change from Baseline( Leukocytes)	-0.60 (1.299)	-0.27 (1.134)	-0.34 (0.686)	-0.80 (1.011)	-0.06 (1.650)
Baseline (Neutrophils)	3.847 (1.0899)	3.493 (0.9737)	3.779 (0.9332)	3.745 (0.9686)	3.394 (1.3264)
Day 14 Change from Baseline (Neutrophils )	-0.374 (1.1794)	0.072 (0.7422)	-0.246 (0.5487)	-0.539 (0.9017)	-0.186 (1.4444)
Baseline (Lymphocytes)	2.148 (0.4905)	2.341 (0.7009)	2.242 (0.6199)	2.320 (0.6467)	2.429 (0.9032)
Day 14 Change from Baseline (Lymphocytes)	-0.172 (0.2900)	-0.301 (0.5336)	-0.107 (0.3652)	-0.237 (0.3901)	0.142 (0.6749)
Baseline ( Monocytes)	0.499 (0.0984)	0.479 (0.1051)	0.505 (0.0990)	0.524 (0.1410)	0.534 (0.1552)
Day 14 Change from Baseline( Monocytes)	-0.033 (0.1117)	-0.030 (0.1324)	0.019 (0.0895)	-0.057 (0.1941)	0.002 (0.1643)
Baseline ( Eosinophils)	0.202 (0.2325)	0.185 (0.1814)	0.177 (0.1090)	0.177 (0.0954)	0.208 (0.1592)
Day 14 Change from Baseline(Eosinophils)	-0.017 (0.0995)	0.021 (0.0719)	-0.006 (0.0549)	0.005 (0.0436)	-0.028 (0.1155)
Baseline(Basophils)	0.041 (0.0305)	0.031 (0.0264)	0.028 (0.0321)	0.027 (0.0301)	0.030 (0.327)
Day 14 Change from Baseline(Basophils)	-0.008 (0.0148)	-0.007 (0.0090)	-0.001 (0.0305)	-0.010 (0.0259)	-0.002 (0.0060)
Baseline( Immature Granulocytes)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 14 Change from Baseline( Immature Granulocytes)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Baseline (Platelets )	263.4 (59.66)	249.1 (61.67)	269.8 (61.40)	261.9 (46.91)	258.2 (52.57)
Day 14 Change from Baseline(Platelets )	8.1 (17.77)	4.5 (33.83)	13.5 (29.67)	21.6 (24.58)	20.8 (74.35)

27. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration
Description	Blood samples for the assessment of Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HB)concentration were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Hemoglobin)	128.9 (8.53)	132.4 (10.64)	128.7 (7.82)	127.7 (8.60)	132.2 (12.60)
Day 14 Change from Baseline (Hemoglobin)	-11.8 (4.99)	-9.0 (7.14)	-14.6 (5.98)	-13.9 (4.66)	-12.1 (6.58)
Baseline (Erythrocytes Mean Corpuscular HB concentration )	328.5 (10.30)	335.2 (9.42)	329.0 (10.22)	328.2 (7.51)	326.8 (10.27)
Day 14 Change from Baseline (Erythrocytes Mean Corpuscular HB concentration)	-0.4 (5.21)	-2.5 (2.34)	-2.3 (6.94)	-0.8 (3.41)	3.2 (4.62)

28. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes
Description	Blood samples for the assessment of Erythrocytes were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	4.467 (0.2503)	4.525 (0.2212)	4.459 (0.2962)	4.365 (0.3678)	4.518 (0.2368)
Day 14 Change from Baseline	-0.421 (0.1750)	-0.301 (0.2694)	-0.511 (0.2111)	-0.485 (0.1903)	-0.425 (0.2297)

29. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume.
Description	Blood samples for the assessment of Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Erythrocytes Mean Corpuscular Volume )	87.87 (5.707)	87.69 (3.890)	87.71 (4.717)	89.42 (6.744)	88.63 (3.150)
Day 14 Change from Baseline (Erythrocytes Mean Corpuscular Volume )	0.44 (1.155)	0.11 (0.799)	0.47 (0.967)	0.49 (1,691)	-0.27 (0.659)
Baseline (Mean Platelet Volume)	9.79 (0.809)	9.91 (1.608)	10.22 (1.565)	10.19 (1.005)	10.05 (1.179)
Day 14 Change from Baseline (Mean Platelet Volume)	-0.14 (0.448)	0.08 (0.412)	-0.24 (0.220)	-0.37 (0.403)	-0.06 (0.216)

30. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Hemoglobin
Description	Blood samples for the assessment of Erythrocytes Mean Corpuscular Hemoglobin were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	28.89 (2.517)	29.50 (1.803)	28.79 (2.217)	29.39 (2.511)	28.89 (1.759)
Day 14 Change from Baseline	0.09 (0.494)	-0.19 (0.263)	0.03 (0.486)	0.15 (0.532)	0.17 (0.317)

31. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Distribution Width.
Description	Blood samples for the assessment of Erythrocytes Distribution Width were collected upon participants admission to the unit. Erythrocytes distribution width (in percentage) = 1 SD of Erythrocyte volume/MCV x 100%
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	27.81 (15.478)	25.52 (15.413)	35.82 (16.476)	30.59 (16.089)	31.48 (17.013)
Day 14 Change from Baseline	-0.15 (0.916)	0.49 (0.863)	-0.05 (1.878)	-0.61 (0.696)	-0.68 (0.778)

32. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hematocrit.
Description	Blood samples for the assessment of Hematocrit were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	39.18 (1.976)	39.63 (2.461)	38.99 (1.788)	38.85 (1.990)	40.02 (2.646)
Day 14 Change from Baseline	-3.51 (1.307)	-2.45 (2.106)	-4.20 (1.877)	-4.13 (1.431)	-3.86 (2.163)

33. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Protein and Albumin.
Description	Blood samples for the assessment of Protein and Albumin were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Protein)	71.8 (4.54)	72.2 (4.13)	74.3 (4.25)	70.5 (4.84)	69.2 (4.22)
Day 14 Change from Baseline(Protein)	-4.0 (3.11)	-2.5 (4.39)	-6.9 (4.89)	-4.1 (2.64)	-2.5 (3.10)
Baseline(Albumin)	42.9 (6.75)	44.3 (1.84)	44.4 (2.53)	44.7 (2.53)	43.2 (2.67)
Day 14 Change from Baseline (Albumin)	-0.6 (6.42)	-2.5 (2.42)	-3.2 (2.08)	0.3 (2.05)	-1.8 (2.44)

34. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase and Creatine Kinase
Description	Blood samples for the assessment of Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase and Creatine Kinase were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Alkaline Phosphatase)	1.587 (0.4829)	1.397 (0.3233)	1.364 (0.3219)	1.397 (0.3271)	1.407 (0.4417)
Day 14 Change from Baseline (Alkaline Phosphatase)	-0.129 (0.3411)	-0.130 (0.2054)	-0.172 (0.1533)	-0.203 (0.2576)	-0.131 (0.2958)
Baseline(Alanine Aminotransferase)	0.295 (0.1302)	0.331 (0.1494)	0.279 (0.1151)	0.313 (0.1281)	0.413 (0.1755)
Day 14 Change from Baseline (Alanine Aminotransferase)	0.108 (0.4103)	-0.049 (0.1053)	0.049 (0,2099)	-0.016 (0.1391)	0.052 (0.3923)
Baseline (Aspartate Aminotransferase)	0.344 (0.0760)	0.355 (0.0632)	0.343 (0.0950)	0.352 (0.0737)	0.401 (0.1976)
Day 14 Change from Baseline (Aspartate Aminotransferase)	0.041 (0.2197)	-0.035 (0.0542)	-0.032 (0.1030)	-0.009 (0.0743)	-0.032 (0.2851)
Baseline (Gamma Glutamyl Transferase)	0.309 (0.1740)	0.324 (0.2085)	0.397 (0.2111)	0.561 (0.7998)	0.372 (0.2272)
Day 14 Change from Baseline (Gamma Glutamyl Transferase)	0.101 (0.3890)	-0.035 (0.0980)	0.001 (0.1606)	-0.190 (0.4620)	0.015 (0.1959)
Baseline (Creatine Kinase)	1.957 (0.8872)	2.047 (1.0146)	1.907 (1.1933)	1.895 (1.2638)	1.886 (1.1854)
Day 14 Change from Baseline (Creatine Kinase)	0.021 (0.9758)	-0.260 (0.4338)	-0.252 (0.5078)	-0.038 (0.5689)	-0.269 (0.5032)

35. Primary Outcome

Title	Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Urate, Bilirubin and Creatinine.
Description	Blood samples for the assessment of Urate, Bilirubin and Creatinine were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Urate)	297.43 (41.896)	318.23 (20.323)	261.74 (57.222)	275.34 (75.528)	212.17 (52.885)
Day 14 Change from Baseline (Urate)	-11.90 (41.380)	-2.95 (28.511)	2.57 (19.706)	-12.76 (28.636)	-7.93 (44.269)
Baseline (Bilirubin)	7.61 (3.500)	8.44 (3.640)	7.19 (2.932)	6.96 (2.652)	7.23 (3.305)
Day 14 Change from Baseline(Bilirubin)	-1.25 (3.225)	-1.15 (2.654)	-1.00 (1.886)	-0.01 (2.599)	0.40 (3.069)
Baseline(Creatinine)	71.162 (11.3215)	67.125 (8.0711)	65.121 (9.8867)	67.891 (9.1636)	11.844 (8.9096)
Day 14 Change from Baseline(Creatinine)	2.652 (6.4810)	-1.885 (7.8090)	-4.168 (7.6761)	-1.297 (6.6136)	-3.605 (5.6665)

36. Primary Outcome

Title	Change From Baseline at Day 14 for Clinical Laboratory Parameters CHEMISTRY: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Phosphate, Glucose, Magnesium and Urea Nitrogen.
Description	Blood samples for the assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, Phosphate, Glucose, Magnesium and Urea Nitrogen were collected upon participant's admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Sodium)	140.7 (2.93)	140.3 (2.05)	140.0 (1.65)	142.3 (3.01)	140.0 (2.83)
Day 14 Change from Baseline (Sodium)	-0.9 (2.91)	-0.7 (2.97)	-0.5 (2.28)	-2.5 (3.23)	0.7 (3.47)
Baseline (Potassium)	4.41 (0.375)	4.22 (0.246)	4.29 (0.374)	4.49 (0.380)	4.14 (0.421)
Day 14 Change from Baseline (Potassium)	0.06 (0.478)	0.22 (0.323)	0.15 (0.427)	-0.06 (0.408)	0.31 (0.614)
Baseline (Chloride)	102.8 (2.94)	102.4 (3.79)	100.7 (2.32)	102.7 (2.84)	101.4 (1.56)
Day 14 Change from Baseline ( Chloride)	-1.2 (3.20)	0.4 (3.16)	1.1 (1.69)	-1.1 (3.02)	0.8 (2.88)
Baseline (Bicarbonate)	26.39 (2.615)	26.60 (2.131)	27.47 (1.642)	26.20 (1.699)	27.62 (3.641)
Day 14 Change from Baseline (Bicarbonate)	1.11 (3.660)	-0.93 (3.575)	1.00 (3.088)	2.00 (2.204)	0.31 (2.626)
Baseline (Calcium)	2.421 (0.0803)	2.401 (0.0730)	2.515 (0.0998)	2.411 (0.0622)	2.382 (0.0928)
Day 14 Change from Baseline (Calcium)	-0.032 (0.1198)	-0.044 (0.1355)	-0.144 (0.1147)	-0.049 (0.0630)	-0.052 (0.1103)
Baseline (Phosphate)	1.240 (0.1510)	1.249 (0.1277)	1.268 (0.1269)	1.280 (0.1115)	1.272 (0.1544)
Day 14 Change from Baseline (Phosphate)	0.026 (0.1602)	-0.045 (0.1457)	-0.052 (0.1096)	0.027 (0.1389)	-0.038 (0.2171)
Baseline (Glucose)	5.457 (0.6417)	5.521 (0.4157)	5.349 (0.4957)	5.483 (0.3943)	5.456 (0.4401)
Day 14 Change from Baseline (Glucose)	-0.113 (0.9083)	-0.278 (0.4006)	-0.173 (0.3412)	-0.098 (0.4245)	0.025 (0.3063)
Baseline (Magnesium)	0.893 (0.0732)	0.885 (0.0588)	0.881 (0.0675)	0.905 (0.0703)	0.896 (0.0836)
Day 14 Change from Baseline (Magnesium)	-0.009 (0.0460)	0.001 (0.0387)	0.001 (0.0529)	0.006 (0.0484)	-0.027 (0.0696)
Baseline (Urea Nitrogen)	5.59 (1.230)	5.47 (1.337)	4.67 (1.274)	5.30 (1.198)	5.21 (1.393)
Day 14 Change from Baseline (Urea Nitrogen)	0.14 (2.359)	-0.14 (1.070)	0.20 (0.826)	0.00 (1.442)	-0.38 (1.488)

37. Primary Outcome

Title	Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate African at Baseline
Description	Blood samples for the assessment of Glomerular Filtration Rate African were collected upon participants admission to the unit.
Time Frame	At Baseline

Outcome Measure Data

Analysis Population Description

Participants with available data reported. Baseline is the last available measurement prior to the first dose of study drug.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Mean (Standard Deviation) [mL/sec/1.73m^2]	1.628 (0.2347)	1.759 (0.1592)	1.580 (0.1846)	1.557 (0.1553)	1.666 (0.1885)

38. Primary Outcome

Title	Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate Caucasian at Baseline
Description	Blood samples for the assessment of Glomerular Filtration Rate Caucasian were collected upon participants admission to the unit.
Time Frame	At Baseline

Outcome Measure Data

Analysis Population Description

Participants with available data reported. Baseline is the last available measurement prior to the first dose of study drug.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Mean (Standard Deviation) [mL/sec/1.73m^2]	1.343 (0.1955)	1.450 (0.1265)	1.300 (0.1503)	1.290 (0.1273)	1.378 (0.1482)

39. Primary Outcome

Title	Change From Baseline at Day 14 for COAGULATION: Prothrombin International Normalized Ratio (INR)
Description	Blood samples for the assessment of Prothrombin International Normalized Ratio were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline	0.993 (0.0428)	1.013 (0.0552)	1.007 (0.0482)	0.991 (0.0465)	0.993 (0.0645)
Day 14 Change from Baseline	-0.007 (0.0546)	-0.038 (0.0471)	0.016 (0.0665)	0.013 (0.0359)	0.057 (0.2311)

40. Primary Outcome

Title	Change From Baseline at Day 14 for COAGULATION: Prothrombin Time and Activated Partial Thromboplastin Time
Description	Blood samples for the assessment of Prothrombin Time and Activated Partial Thromboplastin Time were collected upon participants admission to the unit.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Prothrombin Time )	11.17 (1.871)	11.05 (1.679)	11.91 (1.871)	11.51 (1.757)	11.47 (1.589)
Day 14 Change from Baseline (Prothrombin Time)	-0.15 (0.507)	-0.32 (0.351)	0.12 (0.503)	0.11 (0.291)	0.55 (2.363)
Baseline(Activated Partial Thromboplastin Time)	26.91 (2.435)	27.09 (2.495)	28.14 (2.483)	27.50 (2.872)	27.55 (3.009)
Day 14 Change from Baseline (Activated Partial Thromboplastin Time)	-0.82 (1.350)	-1.80 (1.489)	-0.81 (1.478)	-0.87 (1.396)	0.58 (3.196)

41. Primary Outcome

Title	Heart Rate (HR) - Change From Baseline (Day -1) at Day 14
Description	Heart rate was measured as part of the 12-lead electrocardiogram. Resting ECG recordings were made.Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.
Time Frame	Baseline (day -1) and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Day -1(Predose)	65.7 (9.50)	61.6 (6.43)	65.3 (8.43)	64.5 (5.85)	65.0 (7.16)
Day -1 (0.5 hour)	68.5 (9.54)	64.5 (8.76)	66.7 (10.56)	66.1 (9.13)	68.7 (9.94)
Day -1 (1 hour)	69.8 (9.27)	66.8 (9.58)	66.2 (9.31)	67.6 (5.69)	67.2 (7.77)
Day -1 (1.5 hour)	68.9 (9.26)	67.3 (7.24)	66.5 (9.09)	67.3 (5.38)	67.5 (7.37)
Day -1 (2 hour)	70.2 (10.95)	67.3 (7.81)	65.9 (9.96)	65.2 (4.38)	66.3 (8.36)
Day -1 (2.5 hour)	68.7 (9.02)	69.4 (8.86)	64.6 (10.11)	65.1 (4.19)	68.2 (10.32)
Day -1 (3 hour)	69.4 (9.06)	64.3 (4.91)	65.6 (7.89)	67.9 (5.79)	68.8 (7.51)
Day -1 (4 hour)	68.0 (10.50)	62.8 (6.70)	64.3 (6.20)	63.9 (5.54)	67.5 (8.40)
Day -1 (8 hour)	72.9 (10.38)	64.4 (5.95)	70.2 (10.68)	66.9 (7.17)	70.2 (8.14)
Day -1 (12 hour)	77.0 (9.63)	68.7 (8.96)	73.6 (7.43)	70.7 (7.81)	71.6 (8.69)
Day 14 (Pre dose) Change from Baseline	-0.4 (6.87)	-0.3 (4.08)	0.8 (6.14)	-2.1 (6.96)	-3.8 (8.85)
Day 14 (0.5 hour) Change from Baseline	-2.6 (7.58)	-5.1 (8.48)	-0.9 (10.10)	-4.3 (10.24)	-9.6 (10.13)
Day 14 (1 hour) Change from Baseline	-5.0 (8.66)	-6.7 (9.65)	-0.6 (9.18)	-7.9 (8.35)	-7.7 (6.92)
Day 14 (1.5 hour) Change from Baseline	-5.5 (8.13)	-7.4 (7.24)	-1.5 (7.10)	-7.9 (8.07)	-7.6 (8.08)
Day 14 (2 hour) Change from Baseline	-6.5 (10.98)	-7.9 (7.98)	-2.4 (8.54)	-4.2 (7.90)	-7.0 (6.94)
Day 14 (2.5 hour) Change from Baseline	-4.2 (7.16)	-10.5 (8.60)	-0.3 (7.05)	-4.2 (4.95)	-7.8 (10.48)
Day 14 (3 hour) Change from Baseline	-4.9 (9.94)	-4.6 (5.05)	-0.4 (8.45)	-7.5 (7.74)	-5.7 (9.94)
Day 14 (4 hour) Change from Baseline	-4.3 (8.57)	-2.9 (4.83)	0.2 (8.86)	-2.0 (7.36)	-5.8 (7.62)
Day 14 (8 hour) Change from Baseline	-2.2 (6.22)	0.5 (5.15)	6.8 (8.99)	1.0 (6.47)	-2.3 (9.40)
Day 14 (12 hour) Change from Baseline	-0.9 (5.70)	0.7 (5.74)	2.3 (8.26)	0.0 (5.49)	-3.2 (9.57)

42. Primary Outcome

Title	Mean PR Interval - Change From Baseline (Day -1) at Day 14
Description	PR Interval was measured as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.
Time Frame	Baseline (day -1) and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Day -1 (Predose)	165.3 (22.20)	152.6 (14.30)	165.3 (26.10)	166.6 (26.74)	162.6 (20.52)
Day -1 (0.5 hour)	163.3 (24.69)	155.3 (20.19)	167.1 (26.74)	162.1 (22.13)	162.4 (20.59)
Day -1 (1 hour)	166.3 (23.76)	155.7 (20.43)	166.6 (25.79)	166.5 (24.32)	162.1 (19.82)
Day -1 (1.5 hour)	167.6 (22.91)	158.9 (17.73)	165.9 (21.47)	164.9 (26.07)	162.4 (17.60)
Day -1 (2 hour)	166.9 (25.01)	156.0 (18.95)	167.1 (22.27)	164.9 (25.23)	162.9 (21.16)
Day -1 (2.5 hour)	168.7 (26.32)	155.3 (18.32)	165.8 (26.24)	165.2 (26.51)	160.4 (21.99)
Day -1 (3 hour)	168.0 (25.66)	153.7 (17.61)	170.1 (31.39)	161.8 (23.66)	160.1 (20.10)
Day -1 (4 hour)	165.6 (24.06)	155.4 (17.27)	165.1 (20.73)	163.6 (26.48)	161.6 (16.78)
Day -1 (8 hour)	162.1 (23.67)	152.5 (17.45)	161.7 (22.93)	163.5 (25.00)	156.4 (16.60)
Day -1 (12 hour)	165.7 (26.90)	157.7 (17.41)	158.5 (19.56)	159.0 (21.78)	156.5 (17.71)
Day 14 (Pre dose) Change from Baseline	5.6 (12.32)	1.7 (6.41)	-1.8 (10.85)	-0.3 (9.42)	0.9 (12.78)
Day 14 (0.5 hour) Change from Baseline	8.5 (20.00)	0.4 (6.90)	0.9 (14.64)	4.6 (12.49)	-0.8 (13.90)
Day 14 (1 hour) Change from Baseline	5.6 (15.88)	2.8 (9.03)	-1.0 (14.15)	2.7 (19.24)	1.7 (13.74)
Day 14 (1.5 hour) Change from Baseline	-1.0 (12.86)	-2.8 (9.59)	3.9 (17.63)	-0.5 (11.47)	1.8 (17.08)
Day 14 (2 hour) Change from Baseline	4.1 (12.56)	0.6 (8.85)	-0.9 (17.72)	0.9 (11.82)	4.2 (14.32)
Day 14 (2.5 hour) Change from Baseline	2.2 (9.34)	2.6 (13.33)	0.0 (11.96)	1.8 (12.11)	8.3 (15.96)
Day 14 (3 hour) Change from Baseline	3.8 (11.09)	5.3 (11.40)	-3.1 (10.83)	4.5 (15.01)	4.9 (14.78)
Day 14 (4 hour) Change from Baseline	5.7 (15.13)	1.4 (6.48)	5.2 (20.77)	1.8 (14.49)	2.2 (9.05)
Day 14 (8 hour) Change from Baseline	1.4 (8.66)	2.9 (5.95)	0.1 (15.03)	-3.9 (12.21)	5.2 (6.54)
Day 14 (12 hour) Change from Baseline	-0.4 (8.83)	-3.6 (9.17)	-0.1 (11.07)	2.0 (9.33)	0.9 (10.80)

43. Primary Outcome

Title	Mean QRS Duration - Change From Baseline (Day -1) at Day 14
Description	QRS Duration was measured as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.
Time Frame	Baseline (day -1) and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Day -1(Predose)	88.8 (10.82)	93.6 (8.11)	84.7 (6.39)	89.2 (10.99)	89.5 (11.76)
Day -1 (0.5 hour	88.7 (10.44)	94.5 (7.94)	87.4 (8.44)	88.5 (10.86)	88.9 (10.73)
Day -1 (1 hour)	88.7 (10.22)	93.3 (7.17)	85.2 (7.94)	90.3 (9.91)	91.2 (13.04)
Day -1 (1.5 hour)	89.4 (11.77)	91.7 (8.52)	85.0 (7.98)	89.5 (10.20)	92.2 (11.59)
Day -1 (2 hour)	86.4 (11.08)	90.5 (7.98)	84.0 (5.83)	89.5 (11.15)	89.0 (10.04)
Day -1 (2.5 hour)	87.6 (12.27)	91.5 (8.94)	84.4 (8.22)	89.0 (10.27)	87.8 (10.80)
Day -1 (3 hour)	86.4 (10.10)	92.7 (6.94)	85.7 (9.32)	88.6 (10.10)	87.9 (11.06)
Day -1 (4 hour)	86.2 (11.68)	92.3 (8.26)	85.1 (9.68)	87.7 (11.04)	88.7 (11.53)
Day -1 (8 hour)	85.4 (11.26)	90.9 (9.16)	81.1 (4.41)	85.4 (11.79)	85.3 (11.46)
Day -1 (12 hour)	86.6 (10.53)	92.0 (7.93)	85.5 (9.13)	86.3 (10.55)	88.1 (13.08)
Day 14 (Pre dose) Change from Baseline	-0.7 (3.63)	0.3 (3.89)	-0.8 (4.56)	-0.1 (6.71)	3.1 (7.80)
Day 14 (0.5 hour) Change from Baseline	1.0 (7.64)	-1.2 (5.87)	-3.1 (5.37)	0.4 (6.53)	2.8 (5.06)
Day 14 (1 hour) Change from Baseline	0.7 (6.66)	0.0 (3.57)	-1.6 (7.46)	-0.1 (8.88)	-2.5 (10.73)
Day 14 (1.5 hour) Change from Baseline	-0.8 (6.00)	1.5 (6.83)	-2.0 (6.26)	3.4 (6.74)	-1.8 (8.62)
Day 14 (2 hour) Change from Baseline	1.7 (8.08)	3.2 (5.87)	-0.8 (5.25)	1.9 (8.34)	1.0 (8.08)
Day 14 (2.5 hour) Change from Baseline	1.7 (7.13)	0.9 (4.96)	0.4 (7.02)	1.2 (5.61)	3.4 (7.39)
Day 14 (3 hour) Change from Baseline	2.2 (5.41)	0.5 (4.87)	-1.5 (6.56)	-1.5 (7.06)	2.6 (8.90)
Day 14 (4 hour) Change from Baseline	1.9 (6.27)	0.5 (4.61)	-2.5 (6.44)	14.8 (49.01)	1.7 (7.80)
Day 14 (8 hour) Change from Baseline	-0.3 (3.82)	1.5 (4.63)	0.4 (3.41)	0.9 (6.26)	2.5 (6.05)
Day 14 (12 hour) Change from Baseline	-1.7 (6.91)	0.3 (2.85)	-3.3 (9.28)	-0.5 (5.49)	-0.8 (7.69)

44. Primary Outcome

Title	Mean QT Interval - Change From Baseline (Day -1) at Day 14
Description	QT Interval was measured as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.
Time Frame	Baseline (day -1) and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Day -1 (Predose)	421.8 (31.07)	426.4 (23.73)	412.6 (29.12)	421.8 (22.12)	411.3 (16.01)
Day -1 (0.5 hour	412.4 (27.58)	422.0 (24.00)	410.1 (29.29)	417.7 (22.13)	405.6 (22.19)
Day -1 (1 hour)	412.6 (22.81)	414.6 (21.41)	415.6 (29.17)	414.8 (21.32)	406.5 (21.20)
Day -1 (1.5 hour)	413.7 (23.60)	408.4 (19.91)	408.0 (23.71)	414.9 (21.19)	412.3 (22.31)
Day -1 (2 hour)	407.4 (25.64)	405.8 (19.18)	410.7 (33.40)	413.4 (20.20)	412.7 (22.32)
Day -1 (2.5 hour)	411.3 (27.10)	403.4 (27.70)	410.9 (32.10)	418.9 (32.10)	412.4 (26.30)
Day -1 (3 hour)	407.8 (25.47)	411.9 (22.80)	409.9 (24.92)	410.7 (23.04)	401.2 (23.18)
Day -1 (4 hour)	408.3 (32.47)	414.9 (20.19)	411.2 (21.83)	418.1 (19.01)	407.8 (16.98)
Day -1 (8 hour)	398.9 (29.10)	410.3 (19.54)	396.3 (26.84)	405.7 (22.57)	398.5 (27.65)
Day -1 (12 hour)	389.2 (28.40)	407.1 (22.55)	395.5 (22.33)	402.2 (26.39)	394.4 (28.85)
Day 14 (Pre dose) Change from Baseline	-6.8 (17.03)	0.2 (15.11)	-9.6 (20.16)	-2.1 (24.54)	5.5 (21.03)
Day 14 (0.5 hour) Change from Baseline	2.3 (17.73)	8.7 (13.13)	-2.4 (23.90)	10.2 (25.32)	20.8 (24.94)
Day 14 (1 hour) Change from Baseline	6.9 (18.73)	17.8 (15.93)	-7.9 (28.71)	16.3 (20.43)	17.8 (22.08)
Day 14 (1.5 hour) Change from Baseline	11.7 (22.95)	24.5 (14.95)	-0.5 (19.09)	15.7 (21.82)	17.5 (21.80)
Day 14 (2 hour) Change from Baseline	14.2 (25.19)	25.5 (18.13)	3.6 (25.04)	16.3 (20.76)	16.2 (16.67)
Day 14 (2.5 hour) Change from Baseline	9.5 (25.18)	28.3 (22.66)	1.4 (24.51)	12.9 (21.11)	14.0 (23.04)
Day 14 (3 hour) Change from Baseline	14.2 (28.90)	17.4 (15.42)	1.9 (18.66)	18.3 (23.65)	17.8 (28.64)
Day 14 (4 hour) Change from Baseline	12.6 (22.90)	13.5 (15.04)	-2.8 (23.91)	5.5 (23.97)	18.3 (22.05)
Day 14 (8 hour) Change from Baseline	2.4 (14.71)	-1.9 (12.65)	-14.2 (18.23)	-3.7 (20.76)	6.6 (27.45)
Day 14 (12 hour) Change from Baseline	3.0 (17.62)	-0.8 (13.58)	-12.9 (18.71)	-1.8 (16.37)	7.8 (24.27)

45. Primary Outcome

Title	Mean QTcF Interval (Fridericia's Correction Formula, QTcF) - Change From Baseline (Day -1) at Day 14
Description	Fridericia-corrected QTcF interval was evaluated as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.
Time Frame	Baseline (day -1) and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Day -1(Predose)	432.7 (18.75)	429.0 (16.87)	422.3 (14.41)	431.1 (17.28)	421.8 (20.02)
Day -1 (0.5 hour)	429.2 (16.14)	430.9 (18.81)	422.3 (14.40)	430.1 (16.21)	422.6 (15.35)
Day -1 (1 hour)	432.2 (14.68)	428.3 (14.85)	427.3 (16.15)	430.9 (16.46)	420.8 (13.55)
Day -1 (1.5 hour)	431.7 (18.47)	423.4 (17.60)	420.6 (14.81)	430.5 (15.73)	427.6 (15.24)
Day -1 (2 hour)	427.2 (17.33)	420.5 (13.47)	420.9 (15.57)	424.5 (16.55)	425.2 (15.08)
Day -1 (2.5 hour)	428.7 (19.29)	422.1 (21.46)	418.3 (17.41)	429.9 (18.39)	428.3 (17.29)
Day -1 (3 hour)	426.7 (16.64)	420.3 (18.14)	419.9 (15.56)	427.0 (15.46)	419.0 (17.83)
Day -1 (4 hour)	423.4 (19.52)	420.3 (18.14)	419.9 (14.74)	426.2 (13.33)	423.2 (19.46)
Day -1 (8 hour)	423.8 (16.12)	419.3 (15.99)	415.5 (17.53)	419.7 (16.65)	418.8 (25.31)
Day -1 (12 hour)	421.2 (16.25)	424.2 (13.91)	422.1 (11.25)	423.7 (20.16)	416.8 (20.10)
Day 14 (Pre dose) Change from Baseline	-6.6 (11.74)	0.3 (12.75)	-7.9 (13.31)	-6.6 (22.83)	-3.8 (13.46)
Day 14 (0.5 hour) Change from Baseline	-3.0 (14.97)	-2.9 (9.31)	-4.4 (10.52)	1.1 (14.51)	0.4 (12.92)
Day 14 (1 hour) Change from Baseline	-2.6 (11.94)	2.7 (11.08)	-8.4 (12.88)	-1.2 (18.18)	1.6 (15.34)
Day 14 (1.5 hour) Change from Baseline	0.1 (13.97)	8.3 (15.45)	-3.8 (9.02)	-2.1 (15.16)	0.6 (15.77)
Day 14 (2 hour) Change from Baseline	1.3 (17.40)	8.7 (11.48)	-0.4 (15.25)	6.7 (10.09)	0.8 (12.58)
Day 14 (2.5 hour) Change from Baseline	1.1 (20.94)	5.9 (18.24)	2.3 (13.84)	3.8 (16.62)	-2.3 (12.11)
Day 14 (3 hour) Change from Baseline	3.6 (13.91)	7.0 (17.29)	0.3 (7.71)	2.2 (12.14)	5.5 (15.08)
Day 14 (4 hour) Change from Baseline	4.6 (11.77)	7.1 (14.96)	-3.8 (11.34)	0.1 (15.55)	6.2 (22.76)
Day 14 (8 hour) Change from Baseline	-2.0 (9.55)	-1.1 (10.67)	-1.3 (13.74)	-1.8 (14.03)	2.0 (22.20)
Day 14 (12 hour) Change from Baseline	1.2 (14.43)	1.3 (10.33)	-9.4 (13.78)	-1.3 (17.43)	2.8 (17.21)

46. Primary Outcome

Title	Mean QTcB Interval (Bazett's Correction Formula, QTcB) - Change From Baseline (Day -1) at Day 14
Description	Bazett-corrected QTcB interval was evaluated as part of the 12-lead electrocardiogram. Resting ECG recordings were made. Holter monitors were fitted to participants upon admission in clinic on Day -1 and Day 14.
Time Frame	Baseline (day -1) and day 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Day -1 (Predose)	438.6 (18.07)	430.7 (18.10)	427.6 (13.14)	436.1 (17.61)	417.3 (25.91)
Day -1 (0.5 hour)	438.1 (16.29)	435.6 (21.78)	429.1 (19.47)	436.5 (20.61)	431.8 (20.32)
Day -1 (1 hour)	442.8 (17.55)	435.3 (18.84)	433.7 (18.90)	439.4 (16.23)	428.8 (15.65)
Day -1 (1.5 hour)	441.3 (22.48)	431.3 (20.62)	427.4 (18.56)	438.5 (15.28)	436.0 (16.65)
Day -1 (2 hour)	437.8 (21.87)	428.3 (16.51)	426.6 (17.12)	430.3 (16.49)	432.1 (18.48)
Day -1 (2.5 hour)	438.1 (21.09)	432.1 (22.47)	422.7 (19.67)	435.9 (18.04)	436.9 (21.27)
Day -1 (3 hour)	436.6 (18.42)	425.7 (22.43)	426.7 (16.74)	435.5 (13.93)	428.4 (19.40)
Day -1 (4 hour)	431.6 (18.31)	423.4 (21.21)	424.6 (15.43)	430.3 (14.06)	431.2 (26.00)
Day -1 (8 hour)	437.0 (14.34)	424.2 (17.81)	425.9 (21.39)	427.1 (18.11)	429.5 (27.28)
Day -1 (12 hour)	438.3 (13.91)	433.4 (16.01)	436.4 (9.44)	434.9 (20.98)	428.8 (17.99)
Day 14 (Pre dose) Change from Baseline	-6.7 (14.73)	-0.3 (13.93)	-6.9 (14.02)	-8.9 (25.90)	-8.5 (17.83)
Day 14 (0.5 hour) Change from Baseline	-5.9 (19.59)	-8.9 (17.34)	-5.5 (13.67)	-3.4 (19.47)	-10.3 (17.32)
Day 14 (1 hour) Change from Baseline	-8.0 (16.86)	-4.6 (19.55)	-8.9 (13.33)	-10.3 (23.07)	-7.5 (16.25)
Day 14 (1.5 hour) Change from Baseline	-6.1 (16.42)	0.0 (21.00)	-5.5 (10.36)	-11.1 (18.95)	-8.5 (19.32)
Day 14 (2 hour) Change from Baseline	-5.7 (24.18)	-0.1 (15.10)	-2.9 (19.35)	1.9 (13.13)	-7.5 (16.37)
Day 14 (2.5 hour) Change from Baseline	-3.4 (23.12)	-5.7 (22.17)	2.2 (15.76)	-1.4 (17.37)	-10.8 (16.97)
Day 14 (3 hour) Change from Baseline	-1.6 (13.90)	1.9 (20.81)	-0.4 (11.01)	-6.3 (12.49)	-0.7 (14.57)
Day 14 (4 hour) Change from Baseline	0.4 (13.21)	3.3 (17.73)	-4.2 (12.68)	-2.2 (16.13)	-0.1 (27.06)
Day 14 (8 hour) Change from Baseline	-4.4 (12.46)	-0.8 (13.48)	5.5 (19.09)	-0.9 (14.17)	-0.2 (24.65)
Day 14 (12 hour) Change from Baseline	0.3 (15.11)	2.1 (13.19)	-7.5 (16.64)	-1.2 (20.57)	-0.2 (18.66)

47. Primary Outcome

Title	Nature and Severity of Adverse Events (AEs) up to Day 21
Description	An AE was defined as any untoward medical occurrence in a subject or clinical trial subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product. Serious Adverse Event (SAE) is an adverse event that at any dose: Results in death, Is life-threatening (i.e. the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it was more severe), Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect, Is considered to be an important medical event.
Time Frame	On or after first drug administration up to end of study (Day 21).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Any TEAE	13 72.2%	7 46.7%	11 73.3%	10 66.7%	11 84.6%
Any Mild TEAE	12 66.7%	7 46.7%	10 66.7%	10 66.7%	11 84.6%
Any Moderate TEAE	1 5.6%	1 6.7%	1 6.7%	1 6.7%	1 7.7%
Any Severe TEAE	0 0%	0 0%	0 0%	0 0%	0 0%
Any serious TEAE	9 50%	7 46.7%	7 46.7%	5 33.3%	11 84.6%
Any Causally Related TEAE	9 50%	7 46.7%	7 46.7%	5 33.3%	11 84.6%
Any Causally Related Serious TEAE	11 61.1%	0 0%	0 0%	0 0%	0 0%
Any Life Threatening Serious TEAE	0 0%	0 0%	0 0%	0 0%	0 0%
Any TEAE of Dehydration	0 0%	0 0%	0 0%	0 0%	0 0%
Any Death	0 0%	0 0%	0 0%	0 0%	0 0%

48. Primary Outcome

Title	Withdrawals Due to AEs up to Day 21
Description	An AE was defined as any untoward medical occurrence in a subject or clinical trial subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product. Serious Adverse Event (SAE) is an adverse event that at any dose: Results in death, Is life-threatening (i.e. the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it was more severe), Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect, Is considered to be an important medical event.
Time Frame	On or after first drug administration up to end of study (Day 21)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Any TEAE Leading to Discontinuation of Study Drug	0 0%	0 0%	0 0%	0 0%	0 0%
Any TEAE Leading to Study Discontinuation	0 0%	0 0%	0 0%	0 0%	0 0%

49. Secondary Outcome

Title	Change in Frequency of Hot Flushes From Baseline (Day -1) at Days 7, 14 as Assessed by Skin Conductance
Description	Sternal skin conductance monitors (the Bahr MonitorTM) and the associated algorithm software were supplied by Simplex Scientific LLC (Middleton, USA). Participants were instructed to push a button on the skin conductance monitor when they sensed a hot flush when fitted with the monitor and then provide details of the hot flush in the continuous hot flush diary. Sternal skin conductance monitors were fitted on Day -1 (24 hours±1 hour prior to the planned study drug administration on Day 1) and remained in place until after the Day 7 24-hour assessments were completed (on Day 8). Refitted around 30 minutes prior to study drug administration on Day 14 and remained in place until after the 24-hour assessments were completed on Day 15.
Time Frame	Baseline (day -1) and days 7, 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline ( Day -1)	5.486 (7.148)	8.680 (4.720)	7.787 (6.153)	3.200 (4.945)	5.583 (7.242)
Change from Day -1 to Day 7	-0.857 (6.794)	-3.986 (6.487)	-3.679 (4.670)	-2.197 (4.6090)	0.000 (6.2450)
Change from Day -1 to day 14	-0.139 (8.0619)	-2.642 (6.0682)	-2.913 (6.4202)	0.600 (4.9261)	-2.908 (7.1204)

50. Secondary Outcome

Title	Change From Baseline (Week -1) at Weeks 1, 2 in Frequency of Moderate to Severe Hot Flushes as Measured by Twice Daily Paper Diary Throughout Study
Description	Hot flush frequency and hot flush severity were obtained using the Hot Flush paper Diary. Subjects documented the number of individual hot flushes experienced and rated the severity of each on a scale of 1 to 3 (mild = 1, moderate = 2, severe = 3). The diaries were completed based on recall twice daily, in the morning and evening.
Time Frame	Baseline (week -1) and Week 1 ,Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Week -1)	10.44 (3.866)	12.70 (3.385)	12.04 (3.606)	10.22 (2.976)	9.90 (2.107)
Change from Week -1 to Week 1	-2.53 (3.645)	-1.91 (4.610)	-5.35 (5.153)	-6.36 (3.818)	-4.49 (2.801)
Change from Week -1 to Week 2	-3.87 (4.179)	-3.07 (5.647)	-7.09 (4.915)	-8.62 (3.749)	-6.54 (3.453)

51. Secondary Outcome

Title	Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Severity of Hot Flushes as Measured by Twice Daily Paper Diary
Description	Participants documented the number of individual hot flushes experienced and rated the severity of each on a scale of 1 to 3 (mild = 1, moderate = 2, severe = 3). The diaries were completed based on recall twice daily, in the morning and evening.
Time Frame	Baseline (week -1) and weeks 1, Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Week -1	2.32 (0.304)	2.31 (0.319)	2.20 (0.267)	2.16 (0.379)	2.19 (0.304)
Change from Week -1 to Week 1	-0.30 (0.358)	-0.21 (0.276)	-0.23 (0.318)	-0.51 (0.542)	-0.34 (0.533)
Change from Week -1 to Week 2	-0.34 (0.383)	-0.23 (0.242)	-0.36 (0.359)	-0.88 (0.656)	-0.42 (0.757)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.4641
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 90%; -0.12 to 0.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.127
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.9894
	Comments
	Method	LS means difference
	Comments
Method of Estimation	Estimation Parameter	Linear mixed-effects model
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 90%; -0.21 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.128
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0199
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 90%; -0.52 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.129
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.3907
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 90%; -0.34 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.133
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.5393
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 90%; -0.17 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.166
	Estimation Comments	Change from Week -1 to Week 2

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.7931
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 90%; -0.33 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.169
	Estimation Comments	Change from Week -1 to Week 2

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 90%; -0.92 to -0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.169
	Estimation Comments	Change from Week -1 to Week 2

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.3739
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 90%; -0.45 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.175
	Estimation Comments	Change from Week -1 to Week 2

52. Secondary Outcome

Title	Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Hot Flushes Severity Score as Measured by Twice Daily Paper Diary.
Description	The hot flushes severity score was a composite of the frequency and severity of hot flushes, and was calculated as follows: number of mild hot flushes recorded on Day Y + number of moderate hot flushes recorded on Day Y × 2 + number of severe hot flushes recorded on Day Y × 3. Higher scores mean more severe hot flushes.
Time Frame	Baseline (week -1) and week 1 , 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Week -1	28.06 (11.631)	33.74 (8.875)	32.52 (11.203)	27.87 (7.720)	26.75 (5.416)
Change from Week -1 to Week 1	-6.99 (9.673)	-5.56 (10.907)	-14.48 (14.275)	-17.03 (9.996)	-12.23 (7.284)
Change from Week -1 to Week 2	-10.67 (10.542)	-8.02 (13.031)	-19.19 (14.211)	-22.82 (9.505)	-17.55 (8.953)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0900
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	5.29
	Confidence Interval	(2-Sided) 90%; 0.16 to 10.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.077
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.1487
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-4.46
	Confidence Interval	(2-Sided) 90%; -9.55 to 0.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.053
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-10.18
	Confidence Interval	(2-Sided) 90%; -15.20 to -5.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.015
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0548
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-6.14
	Confidence Interval	(2-Sided) 90%; -11.37 to -0.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.142
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0522
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	6.59
	Confidence Interval	(2-Sided) 90%; 1.03 to 12.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.337
	Estimation Comments	Change from Week -1 to Week 2

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.1326
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-5.07
	Confidence Interval	(2-Sided) 90%; -10.61 to 0.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.329
	Estimation Comments	Change from Week -1 to Week 2

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-12.28
	Confidence Interval	(2-Sided) 90%; -17.73 to -6.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.270
	Estimation Comments	Change from Week -1 to Week 2

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0253
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-7.79
	Confidence Interval	(2-Sided) 90%; -13.47 to -2.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.408
	Estimation Comments	Change from Week -1 to Week 2

53. Secondary Outcome

Title	Change in Frequency From Baseline (Day -1), at Days 7, 14 of Hot Flushes as Measured by Continuous Day Time Diary.
Description	Subjects recorded each hot flush and its severity on a scale of 1 to 3 (mild = 1, moderate = 2, severe = 3) in the hot flush paper diary as they occurred during the day and night.
Time Frame	Baseline(day -1) and Day 7, 14

Outcome Measure Data

Analysis Population Description

Participants with available data reported.

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Day 7 Change from Day -1	-2.8	-1.4	-5.1	-8.3	-5.8
Day 14 Change from Day -1	-3.6	-2.3	-6.0	-8.6	-7.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.3796
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 90%; -1.2 to 4.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.58
	Estimation Comments	Day 7 Change from Day -1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.1413
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 90%; - 4.9 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.55
	Estimation Comments	Day 7 Change from Day -1

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-5.5
	Confidence Interval	(2-Sided) 90%; -8.1 to -2.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.55
	Estimation Comments	Day 7 Change from Day -1

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0624
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 90%; -5.8 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.62
	Estimation Comments	Day 7 Change from Day -1

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.2930
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 90%; -0.7 to 3.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.21
	Estimation Comments	Day 14 Change from Day -1

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0512
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 90%; -4.4 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.21
	Estimation Comments	Day 14 Change from Day -1

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-5.0
	Confidence Interval	(2-Sided) 90%; -7.0 to -3.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.20
	Estimation Comments	Day 14 Change from Day -1

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0080
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 90%; -5.5 to -1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.25
	Estimation Comments	Day 14 Change from Day -1

54. Secondary Outcome

Title	Change From Baseline (Week -1) at Weeks 1, 2 in Night-time Awakenings (NTA) Secondary to Hot Flushes as Measured by Paper Diary
Description	The number of NTAs secondary to hot flushes was the sum of the number of moderate and severe night-time hot flushes recorded the following morning (twice-daily hot flush diary) or recorded contemporaneously on the continuous diary.
Time Frame	Baseline (week-1) and weeks 1 , 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Baseline (Week -1)	4.51 (2.282)	5.61 (1.785)	5.41 (2.337)	4.74 (2.111)	4.76 (1.443)
Change from Week -1 to Week 1	-0.77 (2.066)	-0.80 (2.448)	-2.52 (2.604)	-2.75 (2.335)	-2.07 (1.833)
Change from Week -1 to Week 2	-1.44 (2.128)	-1.12 (2.665)	-3.00 (2.751)	-3.83 (2.008)	-3.02 (2.117)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.1482
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 90%; - 0. 12 to 1.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.574
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0734
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 90%; -1.99 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.571
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0022
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-1.80
	Confidence Interval	(2-Sided) 90%; -2.74 to -0.86
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.565
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0660
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 90%; -2.08 to -0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.589
	Estimation Comments	Change from Week -1 to Week 1

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0593
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 90%; 0.15 to 2.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.613
	Estimation Comments
Other Statistical Analysis		Change from Week -1 to Week 2

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1354
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 90%; -1.95 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.614
	Estimation Comments	Change from Week -1 to Week 2

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-2.20
	Confidence Interval	(2-Sided) 90%; -3.21 to -1.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.603
	Estimation Comments	Change from Week -1 to Week 2

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive Analysis
Statistical Test of Hypothesis	p-Value	0.0309
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-1.38
	Confidence Interval	(2-Sided) 90%; -2.43 to -0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.628
	Estimation Comments	Change from Week -1 to Week 2

55. Secondary Outcome

Title	Change From Baseline (Day-1) to Day 1 and Day 7 in Luteinizing Hormone (AUC0-8)
Description	Change in Luteinizing Hormone(LH) AUC from time zero to 8 hours. Pre-dose samples for LH were taken within 30 minutes prior to dose administration.
Time Frame	baseline (day-1) to day 1 and day 7, pre-dose and post-dose (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0 and 24.0 hours)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	50 mg BAY3427080	100 mg BAY3427080	150 mg BAY3427080	300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.	50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.	150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days	300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
Measure Participants	18	15	15	15	13
Day -1	295.4 (82.64)	295.5 (85.22)	290.8 (85.83)	309.5 (104.38)	261.1 (65.53)
Change from Day -1 to Day 1	14.4 (31.33)	4.7 (35.80)	-10.0 (21.90)	-31.1 (38.28)	-24.6 (32.36)
Change from Day -1 to Day 7	12.4 (57.46)	22.9 (37.07)	10.2 (20.49)	-12.1 (47.30)	-4.4 (33.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive analysis
Statistical Test of Hypothesis	p-Value	0.3768
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-9.7
	Confidence Interval	(2-Sided) 90%; -27.8 to 8.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.88
	Estimation Comments	Change from Day -1 to Day 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive analysis
Statistical Test of Hypothesis	p-Value	0.0248
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-25.0
	Confidence Interval	(2-Sided) 90%; -43.1 to -6.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.89
	Estimation Comments	Change from Day -1 to Day 1

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive analysis
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-43.9
	Confidence Interval	(2-Sided) 90%; -62.1 to -25.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.90
	Estimation Comments	Change from Day -1 to Day 1

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive analysis
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-42.9
	Confidence Interval	(2-Sided) 90%; -61.9 to -23.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.43
	Estimation Comments	Change from Day -1 to Day 1

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive analysis
Statistical Test of Hypothesis	p-Value	0.4819
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	10.4
	Confidence Interval	(2-Sided) 90%; -14.2 to 35.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.76
	Estimation Comments	Change from Day -1 to Day 7

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive analysis
Statistical Test of Hypothesis	p-Value	0.8694
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 90%; -27.1 to 22.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.77
	Estimation Comments	Change from Day -1 to Day 7

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 150 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive analysis
Statistical Test of Hypothesis	p-Value	0.1105
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-23.9
	Confidence Interval	(2-Sided) 90%; -48.6 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.79
	Estimation Comments	Change from Day -1 to Day 7

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 300 mg BAY3427080
	Comments
	Type of Statistical Test	Other
	Comments	Descriptive analysis
Statistical Test of Hypothesis	p-Value	0.2390
	Comments
	Method	Linear mixed-effects model
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-18.4
	Confidence Interval	(2-Sided) 90%; -44.2 to 7.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 15.50
	Estimation Comments	Change from Day -1 to Day 7

Adverse Events

Time Frame	Adverse events data were collected on or after first drug administration up to end of study (Day 21).
Arm/Group Title	Placebo Comparator		50 mg BAY3427080		100 mg BAY3427080		150 mg BAY3427080		300 mg BAY3427080
Arm/Group Description	Placebo to match BAY3427080 (NT-814) capsules administered orally, daily, for 14 days. Number of placebo capsules to match active dose.		50mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.		100 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days.		150 mg of BAY3427080 to be administered as oral capsules, daily, for 14 days		300 mg BAY3427080 to be administered as oral capsules, daily, for 14 days.
All Cause Mortality
	Placebo Comparator		50 mg BAY3427080		100 mg BAY3427080		150 mg BAY3427080		300 mg BAY3427080
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/13 (0%)
Serious Adverse Events
	Placebo Comparator		50 mg BAY3427080		100 mg BAY3427080		150 mg BAY3427080		300 mg BAY3427080
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Comparator		50 mg BAY3427080		100 mg BAY3427080		150 mg BAY3427080		300 mg BAY3427080
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/18 (72.2%)		7/15 (46.7%)		11/15 (73.3%)		10/15 (66.7%)		11/13 (84.6%)
Cardiac disorders
Atrioventricular block first degree	0/18 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/13 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Constipation	0/18 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	1/13 (7.7%)	1
Diarrhoea	0/18 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	1/15 (6.7%)	1	3/13 (23.1%)	3
Dyspepsia	2/18 (11.1%)	2	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/13 (0%)	0
Flatulence	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/13 (7.7%)	1
Frequent bowel movements	0/18 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Nausea	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	2	1/13 (7.7%)	1
Vomiting	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/13 (0%)	0
General disorders
Catheter site related reaction	0/18 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Malaise	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/13 (7.7%)	1
Medical device site erythema	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/13 (0%)	0
Medical device site irritation	1/18 (5.6%)	1	0/15 (0%)	0	1/15 (6.7%)	1	1/15 (6.7%)	1	1/13 (7.7%)	1
Medical device site pruritus	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/13 (0%)	0
Infections and infestations
Otitis externa	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/13 (0%)	0
Viral upper respiratory tract infection	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	3/13 (23.1%)	3
Injury, poisoning and procedural complications
Arthropod bite	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/13 (0%)	0
Contusion	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/13 (7.7%)	1
Investigations
Alanine aminotransferase increased	0/18 (0%)	0	0/15 (0%)	0	2/15 (13.3%)	2	0/15 (0%)	0	0/13 (0%)	0
Aspartate aminotransferase increased	0/18 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/13 (0%)	0
Blood pressure increased	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/18 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/13 (0%)	0
Myalgia	0/18 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	1/15 (6.7%)	1	0/13 (0%)	0
Pain in extremity	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/13 (0%)	0
Nervous system disorders
Dizziness	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Headache	3/18 (16.7%)	3	0/15 (0%)	0	5/15 (33.3%)	5	1/15 (6.7%)	1	6/13 (46.2%)	6
Somnolence	3/18 (16.7%)	3	5/15 (33.3%)	5	2/15 (13.3%)	2	5/15 (33.3%)	5	9/13 (69.2%)	11
Psychiatric disorders
Nightmare	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/13 (7.7%)	1
Reproductive system and breast disorders
Breast tenderness	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Pelvic pain	2/18 (11.1%)	2	3/15 (20%)	3	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/13 (7.7%)	1
Rhinitis allergic	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Oropharyngeal pain	0/18 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Dermatitis contact	5/18 (27.8%)	5	2/15 (13.3%)	2	6/15 (40%)	6	5/15 (33.3%)	5	2/13 (15.4%)	2
Pruritus	0/18 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Pruritus generalised	1/18 (5.6%)	1	0/15 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/13 (0%)	0
Vascular disorders
Phlebitis	0/18 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI is required to postpone communication of results until a joint, multicenter publication of the multicenter study has occurred, or the sponsor confirms that no joint publication will be prepared, or 18 months since completion of the data analysis have passed. The sponsor can review planned publications for up to 60 days and request reasonable amendments. The review period can be extended by up to 6 months in case a patent application is planned.