Evaluation of the Pharmacokinetics and Safety of NT-814 in Post-Menopausal Women With Vasomotor Symptoms

Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of BAY3427080

时间窗: 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.

Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-τ) of BAY3427080

时间窗: 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.

Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of BAY3427080

时间窗: 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.

Maximum Observed Plasma Concentration (Cmax) of BAY3427080

时间窗: 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.

Number of Participants With Clinically Significant Abnormalities on the 12-lead ECGs

时间窗: 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).

Terminal Elimination Half-life (t½) of BAY3427080

时间窗: 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.

Apparent Clearance (CL/F) of BAY3427080

时间窗: 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.

Number of Participants With Clinically Significant Abnormalities Detected Upon Physical Examination.

时间窗: 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).

Number of Participants With Arrhythmias as Assessed by Continuous Holter Monitoring.

时间窗: 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.

Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Standing)

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Sitting)

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Standing)

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Sitting)

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 in Vital Signs: Pulse Rate

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 in Vital Signs: Respiratory Rate

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 in Vital Signs: Oxygen Saturation

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 in Vital Signs: Oral Body Temperature

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 in Vital Signs: Weight

时间窗: Baseline and day 14

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

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

时间窗: Baseline and day 15

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

Change From Baseline at Day 15 for Laboratory Hormones Results: Follicle Stimulating Hormone

时间窗: Baseline and day 15

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

Change From Baseline at Day 15 for Laboratory Hormones Results : Triiodothyronine Uptake

时间窗: Baseline and day 15

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

Change From Baseline at Day 15 for Laboratory Hormones Results: Thyrotropin

时间窗: Baseline and day 15

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

Change From Baseline at Day 15 for Laboratory Hormones Results : Cortisol, Testosterone, Thyroxine and Triiodothyronine

时间窗: Baseline and day 15

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

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

时间窗: 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.

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

时间窗: 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.

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

时间窗: 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.

Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration

时间窗: 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.

Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes

时间窗: Baseline and day 14

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

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

时间窗: 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.

Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Hemoglobin

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Distribution Width.

时间窗: 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%

Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hematocrit.

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Protein and Albumin.

时间窗: Baseline and day 14

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

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

时间窗: 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.

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

时间窗: Baseline and day 14

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

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

时间窗: 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.

Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate African at Baseline

时间窗: At Baseline

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

Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate Caucasian at Baseline

时间窗: At Baseline

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

Change From Baseline at Day 14 for COAGULATION: Prothrombin International Normalized Ratio (INR)

时间窗: Baseline and day 14

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

Change From Baseline at Day 14 for COAGULATION: Prothrombin Time and Activated Partial Thromboplastin Time

时间窗: 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.

Heart Rate (HR) - Change From Baseline (Day -1) at Day 14

时间窗: 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.

Mean PR Interval - Change From Baseline (Day -1) at Day 14

时间窗: 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.

Mean QRS Duration - Change From Baseline (Day -1) at Day 14

时间窗: 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.

Mean QT Interval - Change From Baseline (Day -1) at Day 14

时间窗: 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.

Mean QTcF Interval (Fridericia's Correction Formula, QTcF) - Change From Baseline (Day -1) at Day 14

时间窗: 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.

Mean QTcB Interval (Bazett's Correction Formula, QTcB) - Change From Baseline (Day -1) at Day 14

时间窗: 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.

Nature and Severity of Adverse Events (AEs) up to Day 21

时间窗: 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.

Withdrawals Due to AEs up to Day 21

时间窗: 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.