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

NCT02865538 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 21681
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 3

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.

Conditions

Post-menopausal Vasomotor Symptoms

Keywords

Hot flashes; Post-menopausal

Outcome Measures

Primary Outcomes (48)

• 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)

• 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)

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

  AUC from time zero extrapolated to infinity of BAY3427080 was presented. AUC0-∞ 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)

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

• 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)

• 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)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Change From Baseline at Day 14 in Vital Signs: Weight

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

  Baseline and day 14

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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).

• 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 Outcomes (7)

• 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

• 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

• 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

• 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

• 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

Study Arms (5)

BAY3427080 Placebo

PLACEBO COMPARATOR

Drug: Placebo (for BAY3427080)

50mg BAY3427080

EXPERIMENTAL

Drug: BAY3427080

100mg BAY3427080

EXPERIMENTAL

Drug: BAY3427080

150mg BAY3427080

EXPERIMENTAL

Drug: BAY3427080

300mg BAY3427080

EXPERIMENTAL

Drug: BAY3427080

Interventions

BAY3427080 DRUG

Also known as: NT-814

100mg BAY3427080; 150mg BAY3427080; 300mg BAY3427080; 50mg BAY3427080

Placebo (for BAY3427080) DRUG

BAY3427080 Placebo

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Post-menopausal female subjects experiencing frequent moderate to severe hot flashes.Menopause will be defined as:
• months of spontaneous amenorrhea;
• OR at least 6 weeks' post-surgical bilateral oophorectomy with or without hysterectomy.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead
• Nerre Therapeutics Ltd.: collaborator

Study Sites (3)

Avail Clinical Research

DeLand, Florida, 32720, United States

Location

QPS/MRA (Miami Clinical Research)

Miami, Florida, 33143, United States

Location

ICON Clinical Research Unit

San Antonio, Texas, 78209, United States

Location

Related Publications (1)

• Trower M, Anderson RA, Ballantyne E, Joffe H, Kerr M, Pawsey S. Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial. Menopause. 2020 May;27(5):498-505. doi: 10.1097/GME.0000000000001500.

  PMID: 32068688 DERIVED

MeSH Terms

Conditions

Hot Flashes

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2016
• First Posted: August 12, 2016
• Study Start: August 1, 2016
• Primary Completion: March 28, 2017
• Study Completion: March 28, 2017
• Last Updated: February 7, 2025
• Results First Posted: February 16, 2021

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)