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

Post-menopausal Vasomotor Symptoms Clinical Trial

— RELENT-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02865538
• Other study ID #: 21681
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 1, 2016
• Est. completion date: March 28, 2017

Study information

• Verified date: January 2021
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: March 28, 2017
• Est. primary completion date: March 28, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Post-menopausal Vasomotor Symptoms

Intervention

Drug:
• BAY3427080

• Placebo (for BAY3427080)

Locations

Country	Name	City	State
United States	Avail Clinical Research	DeLand	Florida
United States	QPS/MRA (Miami Clinical Research)	Miami	Florida
United States	ICON Clinical Research Unit	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Nerre Therapeutics Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of BAY3427080	Cmax is the maximum observed plasma concentration of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.	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)
Primary	Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of BAY3427080	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.	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)
Primary	Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-8) of BAY3427080	AUC from time zero extrapolated to infinity of BAY3427080 was presented. AUC0-8 was only estimated following the Day 1 dose.	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)
Primary	Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of BAY3427080	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-t) were taken within 30 minutes prior to dose administration.	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)
Primary	Terminal Elimination Half-life (t½) of BAY3427080	Terminal elimination half-life of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.	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)
Primary	Apparent Clearance (CL/F) of BAY3427080	Apparent clearance of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.	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)
Primary	Number of Participants With Clinically Significant Abnormalities Detected Upon Physical Examination.	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).	At day 14
Primary	Number of Participants With Clinically Significant Abnormalities on the 12-lead ECGs	Reported results are cardiovascular system-examination findings at day 14. Clinically significance was decided by investigator. The findings are presented as abnormal (clinically significant).	At day 14
Primary	Number of Participants With Arrhythmias as Assessed by Continuous Holter Monitoring.	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.	Baseline (day -1) and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Standing)	Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.	Baseline and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Sitting)	Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.	Baseline and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Standing)	Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.	Baseline and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Sitting)	Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.	Baseline and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Pulse Rate	Pulse rate was measured just prior to dosing (approx. 30 mins).	Baseline and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Respiratory Rate	Respiratory rate was measured just prior to dosing (approx. 30 mins).	Baseline and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Oxygen Saturation	Oxygen Saturation was measured just prior to dosing (approx. 30 mins).	Baseline and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Oral Body Temperature	Temperature was measured just prior to dosing (approx. 30 mins).	Baseline and day 14
Primary	Change From Baseline at Day 14 in Vital Signs: Weight	Weight was measured just prior to dosing (approx. 30 mins).	Baseline and day 14
Primary	Change From Baseline at Day 15 for Laboratory Hormones Results : Adrenocorticotropic Hormone (ADTH) and Estradiol.	Blood samples for the assessment of ACTH and Estradiol were collected upon participants admission to the unit.	Baseline and day 15
Primary	Change From Baseline at Day 15 for Laboratory Hormones Results: Follicle Stimulating Hormone	Blood samples for the assessment of Follicle Stimulating were collected upon participants admission to the unit.	Baseline and day 15
Primary	Change From Baseline at Day 15 for Laboratory Hormones Results : Triiodothyronine Uptake	Blood samples for the assessment of Triiodothyronine were collected upon participants admission to the unit.	Baseline and day 15
Primary	Change From Baseline at Day 15 for Laboratory Hormones Results: Thyrotropin	Blood samples for the assessment of Thyrotropin were collected upon participants admission to the unit.	Baseline and day 15
Primary	Change From Baseline at Day 15 for Laboratory Hormones Results : Cortisol, Testosterone, Thyroxine and Triiodothyronine	Blood samples for the assessment of Cortisol, Testosterone, Thyroxine and Triiodothyronine were collected upon participants admission to the unit.	Baseline and day 15
Primary	Change From Baseline at Day 14 for Clinical Laboratory Parameters LIPIDS : Cholesterol, Triglycerides, HDL Cholesterol and LDL Cholesterol.	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.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Immature Granulocytes.	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.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Clinical Laboratory Parameters HEMATOLOGY: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Immature Granulocytes and Platelets.	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.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration	Blood samples for the assessment of Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HB)concentration were collected upon participants admission to the unit.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes	Blood samples for the assessment of Erythrocytes were collected upon participants admission to the unit.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume.	Blood samples for the assessment of Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume were collected upon participants admission to the unit.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples for the assessment of Erythrocytes Mean Corpuscular Hemoglobin were collected upon participants admission to the unit.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Distribution Width.	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%	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hematocrit.	Blood samples for the assessment of Hematocrit were collected upon participants admission to the unit.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Protein and Albumin.	Blood samples for the assessment of Protein and Albumin were collected upon participants admission to the unit.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase and Creatine Kinase	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.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Urate, Bilirubin and Creatinine.	Blood samples for the assessment of Urate, Bilirubin and Creatinine were collected upon participants admission to the unit.	Baseline and day 14
Primary	Change From Baseline at Day 14 for Clinical Laboratory Parameters CHEMISTRY: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Phosphate, Glucose, Magnesium and Urea Nitrogen.	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.	Baseline and day 14
Primary	Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate African at Baseline	Blood samples for the assessment of Glomerular Filtration Rate African were collected upon participants admission to the unit.	At Baseline
Primary	Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate Caucasian at Baseline	Blood samples for the assessment of Glomerular Filtration Rate Caucasian were collected upon participants admission to the unit.	At Baseline
Primary	Change From Baseline at Day 14 for COAGULATION: Prothrombin International Normalized Ratio (INR)	Blood samples for the assessment of Prothrombin International Normalized Ratio were collected upon participants admission to the unit.	Baseline and day 14
Primary	Change From Baseline at Day 14 for COAGULATION: Prothrombin Time and Activated Partial Thromboplastin Time	Blood samples for the assessment of Prothrombin Time and Activated Partial Thromboplastin Time were collected upon participants admission to the unit.	Baseline and day 14
Primary	Heart Rate (HR) - Change From Baseline (Day -1) at 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.	Baseline (day -1) and day 14
Primary	Mean PR Interval - Change From Baseline (Day -1) at 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.	Baseline (day -1) and day 14
Primary	Mean QRS Duration - Change From Baseline (Day -1) at 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.	Baseline (day -1) and day 14
Primary	Mean QT Interval - Change From Baseline (Day -1) at 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.	Baseline (day -1) and day 14
Primary	Mean QTcF Interval (Fridericia's Correction Formula, QTcF) - Change From Baseline (Day -1) at 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.	Baseline (day -1) and day 14
Primary	Mean QTcB Interval (Bazett's Correction Formula, QTcB) - Change From Baseline (Day -1) at 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.	Baseline (day -1) and day 14
Primary	Nature and Severity of Adverse Events (AEs) up to 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.	On or after first drug administration up to end of study (Day 21).
Primary	Withdrawals Due to AEs up to 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.	On or after first drug administration up to end of study (Day 21)
Secondary	Change in Frequency of Hot Flushes From Baseline (Day -1) at Days 7, 14 as Assessed by Skin Conductance	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.	Baseline (day -1) and days 7, 14
Secondary	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	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.	Baseline (week -1) and Week 1 ,Week 2
Secondary	Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Severity of Hot Flushes as Measured by Twice Daily Paper Diary	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.	Baseline (week -1) and weeks 1, Week 2
Secondary	Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Hot Flushes Severity Score as Measured by Twice Daily Paper Diary.	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.	Baseline (week -1) and week 1 , 2
Secondary	Change in Frequency From Baseline (Day -1), at Days 7, 14 of Hot Flushes as Measured by Continuous Day Time Diary.	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.	Baseline(day -1) and Day 7, 14
Secondary	Change From Baseline (Week -1) at Weeks 1, 2 in Night-time Awakenings (NTA) Secondary to Hot Flushes as Measured by Paper Diary	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.	Baseline (week-1) and weeks 1 , 2
Secondary	Change From Baseline (Day-1) to Day 1 and Day 7 in Luteinizing Hormone (AUC0-8)	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.	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)