Title
Evaluation of the Pharmacokinetics and Safety of BAY3427080 (NT-814) in Post-Menopausal Women With Vasomotor Symptoms
Evaluation of the Pharmacokinetics and Safety of NT-814 in Post-Menopausal Women With Vasomotor Symptoms
Phase
Phase 1/Phase 2Lead Sponsor
NeRRe Therapeutics Ltd.Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
Post-menopausal Vasomotor SymptomsIntervention/Treatment
nt-814 ...Study Participants
76This 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.
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.
| Event Type | Organ System | Event Term | Placebo Comparator | 50 mg BAY3427080 | 100 mg BAY3427080 | 150 mg BAY3427080 | 300 mg BAY3427080 |
|---|
Blood samples for the assessment of Cortisol, Testosterone, Thyroxine and Triiodothyronine were collected upon participants admission to the unit.
Cmax is the maximum observed plasma concentration of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.
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.
AUC from time zero extrapolated to infinity of BAY3427080 was presented. AUC0-∞ was only estimated following the Day 1 dose.
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.
Terminal elimination half-life of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.
Apparent clearance of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.
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).
Reported results are cardiovascular system-examination findings at day 14. Clinically significance was decided by investigator. The findings are presented as abnormal (clinically significant).
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.
Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.
Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.
Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.
Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.
Pulse rate was measured just prior to dosing (approx. 30 mins).
Respiratory rate was measured just prior to dosing (approx. 30 mins).
Oxygen Saturation was measured just prior to dosing (approx. 30 mins).
Temperature was measured just prior to dosing (approx. 30 mins).
Weight was measured just prior to dosing (approx. 30 mins).
Blood samples for the assessment of ACTH and Estradiol were collected upon participants admission to the unit.
Blood samples for the assessment of Follicle Stimulating were collected upon participants admission to the unit.
Blood samples for the assessment of Triiodothyronine were collected upon participants admission to the unit.
Blood samples for the assessment of Thyrotropin were collected upon participants admission to the unit.
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.
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.
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.
Blood samples for the assessment of Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HB)concentration were collected upon participants admission to the unit.
Blood samples for the assessment of Erythrocytes were collected upon participants admission to the unit.
Blood samples for the assessment of Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume were collected upon participants admission to the unit.
Blood samples for the assessment of Erythrocytes Mean Corpuscular Hemoglobin were collected upon participants admission to the unit.
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%
Blood samples for the assessment of Hematocrit were collected upon participants admission to the unit.
Blood samples for the assessment of Protein and Albumin were collected upon participants admission to the unit.
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.
Blood samples for the assessment of Urate, Bilirubin and Creatinine were collected upon participants admission to the unit.
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.
Blood samples for the assessment of Glomerular Filtration Rate African were collected upon participants admission to the unit.
Blood samples for the assessment of Glomerular Filtration Rate Caucasian were collected upon participants admission to the unit.
Blood samples for the assessment of Prothrombin International Normalized Ratio were collected upon participants admission to the unit.
Blood samples for the assessment of Prothrombin Time and Activated Partial Thromboplastin Time were collected upon participants admission to the unit.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
