Clinical trial NCT02865538: Evaluation of the Pharmacokinetics and Safety of BAY3427080 (NT-814) in Post-Menopausal Women With Vasomotor Symptoms
Official title: Evaluation of the Pharmacokinetics and Safety of NT-814 in Post-Menopausal Women With Vasomotor Symptoms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Post-menopausal Vasomotor Symptoms
Keywords: Hot flashes
Post-menopausal
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Nerre Therapeutics Ltd.
First posted: 2016-08-12
Enrollment: 76
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of BAY3427080
timeFrame: 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)
measure: Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of BAY3427080
timeFrame: 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)
measure: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of BAY3427080
timeFrame: 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)
measure: Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-τ) of BAY3427080
timeFrame: 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)
measure: Terminal Elimination Half-life (t½) of BAY3427080
timeFrame: 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)
measure: Apparent Clearance (CL/F) of BAY3427080
timeFrame: 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)
measure: Number of Participants With Clinically Significant Abnormalities Detected Upon Physical Examination.
timeFrame: At day 14
measure: Number of Participants With Clinically Significant Abnormalities on the 12-lead ECGs
timeFrame: At day 14
measure: Number of Participants With Arrhythmias as Assessed by Continuous Holter Monitoring.
timeFrame: Baseline (day -1) and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Standing)
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Sitting)
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Standing)
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Sitting)
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Pulse Rate
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Respiratory Rate
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Oxygen Saturation
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Oral Body Temperature
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 in Vital Signs: Weight
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 15 for Laboratory Hormones Results : Adrenocorticotropic Hormone (ADTH) and Estradiol.
timeFrame: Baseline and day 15
measure: Change From Baseline at Day 15 for Laboratory Hormones Results: Follicle Stimulating Hormone
timeFrame: Baseline and day 15
measure: Change From Baseline at Day 15 for Laboratory Hormones Results : Triiodothyronine Uptake
timeFrame: Baseline and day 15
measure: Change From Baseline at Day 15 for Laboratory Hormones Results: Thyrotropin
timeFrame: Baseline and day 15
measure: Change From Baseline at Day 15 for Laboratory Hormones Results : Cortisol, Testosterone, Thyroxine and Triiodothyronine
timeFrame: Baseline and day 15
measure: Change From Baseline at Day 14 for Clinical Laboratory Parameters LIPIDS : Cholesterol, Triglycerides, HDL Cholesterol and LDL Cholesterol.
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Immature Granulocytes.
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Clinical Laboratory Parameters HEMATOLOGY: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Immature Granulocytes and Platelets.
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume.
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Distribution Width.
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hematocrit.
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Protein and Albumin.
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase and Creatine Kinase
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Urate, Bilirubin and Creatinine.
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for Clinical Laboratory Parameters CHEMISTRY: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Phosphate, Glucose, Magnesium and Urea Nitrogen.
timeFrame: Baseline and day 14
measure: Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate African at Baseline
timeFrame: At Baseline
measure: Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate Caucasian at Baseline
timeFrame: At Baseline
measure: Change From Baseline at Day 14 for COAGULATION: Prothrombin International Normalized Ratio (INR)
timeFrame: Baseline and day 14
measure: Change From Baseline at Day 14 for COAGULATION: Prothrombin Time and Activated Partial Thromboplastin Time
timeFrame: Baseline and day 14
measure: Heart Rate (HR) - Change From Baseline (Day -1) at Day 14
timeFrame: Baseline (day -1) and day 14
measure: Mean PR Interval - Change From Baseline (Day -1) at Day 14
timeFrame: Baseline (day -1) and day 14
measure: Mean QRS Duration - Change From Baseline (Day -1) at Day 14
timeFrame: Baseline (day -1) and day 14
measure: Mean QT Interval - Change From Baseline (Day -1) at Day 14
timeFrame: Baseline (day -1) and day 14
measure: Mean QTcF Interval (Fridericia's Correction Formula, QTcF) - Change From Baseline (Day -1) at Day 14
timeFrame: Baseline (day -1) and day 14
measure: Mean QTcB Interval (Bazett's Correction Formula, QTcB) - Change From Baseline (Day -1) at Day 14
timeFrame: Baseline (day -1) and day 14
measure: Nature and Severity of Adverse Events (AEs) up to Day 21
timeFrame: On or after first drug administration up to end of study (Day 21).
measure: Withdrawals Due to AEs up to Day 21
timeFrame: On or after first drug administration up to end of study (Day 21)
Secondary outcomes:
measure: Change in Frequency of Hot Flushes From Baseline (Day -1) at Days 7, 14 as Assessed by Skin Conductance
timeFrame: Baseline (day -1) and days 7, 14
measure: 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
timeFrame: Baseline (week -1) and Week 1 ,Week 2
measure: Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Severity of Hot Flushes as Measured by Twice Daily Paper Diary
timeFrame: Baseline (week -1) and weeks 1, Week 2
measure: Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Hot Flushes Severity Score as Measured by Twice Daily Paper Diary.
timeFrame: Baseline (week -1) and week 1 , 2
measure: Change in Frequency From Baseline (Day -1), at Days 7, 14 of Hot Flushes as Measured by Continuous Day Time Diary.
timeFrame: Baseline(day -1) and Day 7, 14
measure: Change From Baseline (Week -1) at Weeks 1, 2 in Night-time Awakenings (NTA) Secondary to Hot Flushes as Measured by Paper Diary
timeFrame: Baseline (week-1) and weeks 1 , 2
measure: Change From Baseline (Day-1) to Day 1 and Day 7 in Luteinizing Hormone (AUC0-8)
timeFrame: 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)
Other outcomes:
Locations:
city: DeLand
country: United States
facility: Avail Clinical Research
state: Florida
city: Miami
country: United States
facility: QPS/MRA (Miami Clinical Research)
state: Florida
city: San Antonio
country: United States
facility: ICON Clinical Research Unit
state: Texas
Study officials:
References:
citation: 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.