Phase 2 N=76 Randomized Quadruple-blind Treatment

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

Post-menopausal Vasomotor Symptoms

Bottom Line

View on ClinicalTrials.gov: NCT02865538 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Feb 2021

Primary outcome: Primary: Maximum Observed Plasma Concentration (Cmax) of BAY3427080 — 502.62; 731.69; 911.48; 1576.01 ng/mL

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: BAY3427080 (Drug); Placebo (for BAY3427080) (Drug)
Age: Adult, Older Adult · 45+ yrs
Sex: Female
Sponsor: Bayer
Primary completion: Mar 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Maximum Observed Plasma Concentration (Cmax) of BAY3427080	502.62; 731.69; 911.48; 1576.01; 548.60; 809.48	—
PRIMARY Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of BAY3427080	1.360; 1.320; 1.521; 1.471; 1.432; 1.623	—
PRIMARY Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of BAY3427080	2018.68; 1545.58; 1151.87; 6249.52	—
PRIMARY Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-τ) of BAY3427080	1400.167; 2341.882; 3012.793; 6527.569; 2506.97; 4472.76	—
PRIMARY Terminal Elimination Half-life (t½) of BAY3427080	2.409; 1.903; 3.965; 3.142; 2.443; 3.303	—
PRIMARY Apparent Clearance (CL/F) of BAY3427080	24.769; 64.700; 130.223; 48.004; 19.944; 22.358	—
PRIMARY Number of Participants With Clinically Significant Abnormalities Detected Upon Physical Examination.	1; 0; 2; 1; 2	—
PRIMARY Number of Participants With Clinically Significant Abnormalities on the 12-lead ECGs	0; 0; 1; 0; 0	—
PRIMARY Number of Participants With Arrhythmias as Assessed by Continuous Holter Monitoring.	0; 0; 1; 0; 0; 2	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Standing)	80.11; 76.07; 77.67; 78.93; 77.92; 1.11	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Sitting)	77.72; 74.27; 77.20; 74.80; 74.15; 0.11	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Standing)	117.83; 114.60; 121.33; 118.87; 114.77; 5.11	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Sitting)	116.39; 113.80; 119.07; 117.20; 114.15; 4.17	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Pulse Rate	69.89; 66.00; 69.20; 68.40; 72.62; 1.06	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Respiratory Rate	15.39; 15.47; 15.73; 15.60; 15.85; -0.11	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Oxygen Saturation	98.50; 98.40; 97.87; 97.67; 97.31; -0.61	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Oral Body Temperature	36.77; 36.65; 36.79; 36.71; 36.77; -0.04	—
PRIMARY Change From Baseline at Day 14 in Vital Signs: Weight	73.25; 70.85; 73.47; 72.10; 72.73; 0.36	—
PRIMARY Change From Baseline at Day 15 for Laboratory Hormones Results : Adrenocorticotropic Hormone (ADTH) and Estradiol.	5.34; 4.17; 3.87; 3.55; 3.27; -0.49	—
PRIMARY Change From Baseline at Day 15 for Laboratory Hormones Results: Follicle Stimulating Hormone	76.01; 100.87; 77.78; 88.77; 70.59; 5.98	—
PRIMARY Change From Baseline at Day 15 for Laboratory Hormones Results : Triiodothyronine Uptake	32.300; 30.800; 30.838; 30.671; -0.720; -0.700	—
PRIMARY Change From Baseline at Day 15 for Laboratory Hormones Results: Thyrotropin	2.658; 1.800; 2.451; 2.785; 2.330; -0.959	—
PRIMARY Change From Baseline at Day 15 for Laboratory Hormones Results : Cortisol, Testosterone, Thyroxine and Triiodothyronine	348.60; 337.16; 345.91; 251.66; 230.42; 15.94	—
PRIMARY Change From Baseline at Day 14 for Clinical Laboratory Parameters LIPIDS : Cholesterol, Triglycerides, HDL Cholesterol and LDL Cholesterol.	5.434; 5.471; 5.391; 5.804; 5.393; 0.088	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Immature Granulocytes.	56.53; 53.31; 55.65; 54.78; 50.92; -0.29	—
PRIMARY Change From Baseline at Day 14 for Clinical Laboratory Parameters HEMATOLOGY: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Immature Granulocytes and Platelets.	6.73; 6.54; 6.75; 6.78; 6.60; -0.60	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration	128.9; 132.4; 128.7; 127.7; 132.2; -11.8	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes	4.467; 4.525; 4.459; 4.365; 4.518; -0.421	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume.	87.87; 87.69; 87.71; 89.42; 88.63; 0.44	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Hemoglobin	28.89; 29.50; 28.79; 29.39; 28.89; 0.09	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Distribution Width.	27.81; 25.52; 35.82; 30.59; 31.48; -0.15	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hematocrit.	39.18; 39.63; 38.99; 38.85; 40.02; -3.51	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Protein and Albumin.	71.8; 72.2; 74.3; 70.5; 69.2; -4.0	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase and Creatine Kinase	1.587; 1.397; 1.364; 1.397; 1.407; -0.129	—
PRIMARY Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Urate, Bilirubin and Creatinine.	297.43; 318.23; 261.74; 275.34; 212.17; -11.90	—
PRIMARY Change From Baseline at Day 14 for Clinical Laboratory Parameters CHEMISTRY: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Phosphate, Glucose, Magnesium and Urea Nitrogen.	140.7; 140.3; 140.0; 142.3; 140.0; -0.9	—
PRIMARY Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate African at Baseline	1.628; 1.759; 1.580; 1.557; 1.666	—
PRIMARY Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate Caucasian at Baseline	1.343; 1.450; 1.300; 1.290; 1.378	—
PRIMARY Change From Baseline at Day 14 for COAGULATION: Prothrombin International Normalized Ratio (INR)	0.993; 1.013; 1.007; 0.991; 0.993; -0.007	—
PRIMARY Change From Baseline at Day 14 for COAGULATION: Prothrombin Time and Activated Partial Thromboplastin Time	11.17; 11.05; 11.91; 11.51; 11.47; -0.15	—
PRIMARY Heart Rate (HR) - Change From Baseline (Day -1) at Day 14	65.7; 61.6; 65.3; 64.5; 65.0; 68.5	—
PRIMARY Mean PR Interval - Change From Baseline (Day -1) at Day 14	165.3; 152.6; 165.3; 166.6; 162.6; 163.3	—
PRIMARY Mean QRS Duration - Change From Baseline (Day -1) at Day 14	88.8; 93.6; 84.7; 89.2; 89.5; 88.7	—
PRIMARY Mean QT Interval - Change From Baseline (Day -1) at Day 14	421.8; 426.4; 412.6; 421.8; 411.3; 412.4	—
PRIMARY Mean QTcF Interval (Fridericia's Correction Formula, QTcF) - Change From Baseline (Day -1) at Day 14	432.7; 429.0; 422.3; 431.1; 421.8; 429.2	—
PRIMARY Mean QTcB Interval (Bazett's Correction Formula, QTcB) - Change From Baseline (Day -1) at Day 14	438.6; 430.7; 427.6; 436.1; 417.3; 438.1	—
PRIMARY Nature and Severity of Adverse Events (AEs) up to Day 21	13; 7; 11; 10; 11; 12	—
PRIMARY Withdrawals Due to AEs up to Day 21	0; 0; 0; 0; 0; 0	—
SECONDARY Change in Frequency of Hot Flushes From Baseline (Day -1) at Days 7, 14 as Assessed by Skin Conductance	5.486; 8.680; 7.787; 3.200; 5.583; -0.857	—
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	10.44; 12.70; 12.04; 10.22; 9.90; -2.53	—
SECONDARY Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Severity of Hot Flushes as Measured by Twice Daily Paper Diary	2.32; 2.31; 2.20; 2.16; 2.19; -0.30	0.4641
SECONDARY Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Hot Flushes Severity Score as Measured by Twice Daily Paper Diary.	28.06; 33.74; 32.52; 27.87; 26.75; -6.99	0.0900
SECONDARY Change in Frequency From Baseline (Day -1), at Days 7, 14 of Hot Flushes as Measured by Continuous Day Time Diary.	-2.8; -1.4; -5.1; -8.3; -5.8; -3.6	0.3796
SECONDARY Change From Baseline (Week -1) at Weeks 1, 2 in Night-time Awakenings (NTA) Secondary to Hot Flushes as Measured by Paper Diary	4.51; 5.61; 5.41; 4.74; 4.76; -0.77	0.1482
SECONDARY Change From Baseline (Day-1) to Day 1 and Day 7 in Luteinizing Hormone (AUC0-8)	295.4; 295.5; 290.8; 309.5; 261.1; 14.4	0.3768

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02865538). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.