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Completed

NCT Number: NCT02865538

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

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.

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Key information

Conditions

Post-menopausal Vasomotor Symptoms Hot Flashes Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

45 year–65 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Avail Clinical Research, DeLand, Florida, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

BAY3427080

Drug

Other names: NT-814

Placebo (for BAY3427080)

Drug

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of BAY3427080

    Time frame: 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)

    Cmax is the maximum observed plasma concentration of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.

  2. Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of BAY3427080

    Time frame: 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 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.

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

    Time frame: 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)

    AUC from time zero extrapolated to infinity of BAY3427080 was presented. AUC0-∞ was only estimated following the Day 1 dose.

  4. Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-τ) of BAY3427080

    Time frame: 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 (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.

  5. Terminal Elimination Half-life (t½) of BAY3427080

    Time frame: 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 of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.

  6. Apparent Clearance (CL/F) of BAY3427080

    Time frame: 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 of BAY3427080 was presented. Blood samples were taken within 30 minutes prior to dose administration.

  7. Number of Participants With Clinically Significant Abnormalities Detected Upon Physical Examination.

    Time frame: At day 14

    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).

  8. Number of Participants With Clinically Significant Abnormalities on the 12-lead ECGs

    Time frame: At day 14

    Reported results are cardiovascular system-examination findings at day 14. Clinically significance was decided by investigator. The findings are presented as abnormal (clinically significant).

  9. Number of Participants With Arrhythmias as Assessed by Continuous Holter Monitoring.

    Time frame: Baseline (day -1) and day 14

    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.

  10. Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Standing)

    Time frame: Baseline and day 14

    Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.

  11. Change From Baseline at Day 14 in Vital Signs: Diastolic Blood Pressure (Sitting)

    Time frame: Baseline and day 14

    Diastolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.

  12. Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Standing)

    Time frame: Baseline and day 14

    Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in standing position.

  13. Change From Baseline at Day 14 in Vital Signs: Systolic Blood Pressure (Sitting)

    Time frame: Baseline and day 14

    Systolic Blood Pressure was measured just prior to dosing (approx. 30 mins) in sitting position.

  14. Change From Baseline at Day 14 in Vital Signs: Pulse Rate

    Time frame: Baseline and day 14

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

  15. Change From Baseline at Day 14 in Vital Signs: Respiratory Rate

    Time frame: Baseline and day 14

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

  16. Change From Baseline at Day 14 in Vital Signs: Oxygen Saturation

    Time frame: Baseline and day 14

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

  17. Change From Baseline at Day 14 in Vital Signs: Oral Body Temperature

    Time frame: Baseline and day 14

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

  18. Change From Baseline at Day 14 in Vital Signs: Weight

    Time frame: Baseline and day 14

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

  19. Change From Baseline at Day 15 for Laboratory Hormones Results : Adrenocorticotropic Hormone (ADTH) and Estradiol.

    Time frame: Baseline and day 15

    Blood samples for the assessment of ACTH and Estradiol were collected upon participants admission to the unit.

  20. Change From Baseline at Day 15 for Laboratory Hormones Results: Follicle Stimulating Hormone

    Time frame: Baseline and day 15

    Blood samples for the assessment of Follicle Stimulating were collected upon participants admission to the unit.

  21. Change From Baseline at Day 15 for Laboratory Hormones Results : Triiodothyronine Uptake

    Time frame: Baseline and day 15

    Blood samples for the assessment of Triiodothyronine were collected upon participants admission to the unit.

  22. Change From Baseline at Day 15 for Laboratory Hormones Results: Thyrotropin

    Time frame: Baseline and day 15

    Blood samples for the assessment of Thyrotropin were collected upon participants admission to the unit.

  23. Change From Baseline at Day 15 for Laboratory Hormones Results : Cortisol, Testosterone, Thyroxine and Triiodothyronine

    Time frame: Baseline and day 15

    Blood samples for the assessment of Cortisol, Testosterone, Thyroxine and Triiodothyronine were collected upon participants admission to the unit.

  24. Change From Baseline at Day 14 for Clinical Laboratory Parameters LIPIDS : Cholesterol, Triglycerides, HDL Cholesterol and LDL Cholesterol.

    Time frame: Baseline and day 14

    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.

  25. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Immature Granulocytes.

    Time frame: Baseline and day 14

    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.

  26. Change From Baseline at Day 14 for Clinical Laboratory Parameters HEMATOLOGY: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Immature Granulocytes and Platelets.

    Time frame: Baseline and day 14

    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.

  27. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration

    Time frame: Baseline and day 14

    Blood samples for the assessment of Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HB)concentration were collected upon participants admission to the unit.

  28. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes

    Time frame: Baseline and day 14

    Blood samples for the assessment of Erythrocytes were collected upon participants admission to the unit.

  29. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume.

    Time frame: Baseline and day 14

    Blood samples for the assessment of Erythrocytes Mean Corpuscular Volume and Mean Platelet Volume were collected upon participants admission to the unit.

  30. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Mean Corpuscular Hemoglobin

    Time frame: Baseline and day 14

    Blood samples for the assessment of Erythrocytes Mean Corpuscular Hemoglobin were collected upon participants admission to the unit.

  31. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Erythrocytes Distribution Width.

    Time frame: Baseline and day 14

    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%

  32. Change From Baseline at Day 14 for Laboratory Parameters HEMATOLOGY: Hematocrit.

    Time frame: Baseline and day 14

    Blood samples for the assessment of Hematocrit were collected upon participants admission to the unit.

  33. Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Protein and Albumin.

    Time frame: Baseline and day 14

    Blood samples for the assessment of Protein and Albumin were collected upon participants admission to the unit.

  34. Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase and Creatine Kinase

    Time frame: Baseline and day 14

    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.

  35. Change From Baseline at Day 14 for Laboratory Parameters CHEMISTRY: Urate, Bilirubin and Creatinine.

    Time frame: Baseline and day 14

    Blood samples for the assessment of Urate, Bilirubin and Creatinine were collected upon participants admission to the unit.

  36. Change From Baseline at Day 14 for Clinical Laboratory Parameters CHEMISTRY: Sodium, Potassium, Chloride, Bicarbonate, Calcium, Phosphate, Glucose, Magnesium and Urea Nitrogen.

    Time frame: Baseline and day 14

    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.

  37. Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate African at Baseline

    Time frame: At Baseline

    Blood samples for the assessment of Glomerular Filtration Rate African were collected upon participants admission to the unit.

  38. Laboratory Parameters CHEMISTRY: Glomerular Filtration Rate Caucasian at Baseline

    Time frame: At Baseline

    Blood samples for the assessment of Glomerular Filtration Rate Caucasian were collected upon participants admission to the unit.

  39. Change From Baseline at Day 14 for COAGULATION: Prothrombin International Normalized Ratio (INR)

    Time frame: Baseline and day 14

    Blood samples for the assessment of Prothrombin International Normalized Ratio were collected upon participants admission to the unit.

  40. Change From Baseline at Day 14 for COAGULATION: Prothrombin Time and Activated Partial Thromboplastin Time

    Time frame: Baseline and day 14

    Blood samples for the assessment of Prothrombin Time and Activated Partial Thromboplastin Time were collected upon participants admission to the unit.

  41. Heart Rate (HR) - Change From Baseline (Day -1) at Day 14

    Time frame: Baseline (day -1) and 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.

  42. Mean PR Interval - Change From Baseline (Day -1) at Day 14

    Time frame: Baseline (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.

  43. Mean QRS Duration - Change From Baseline (Day -1) at Day 14

    Time frame: Baseline (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.

  44. Mean QT Interval - Change From Baseline (Day -1) at Day 14

    Time frame: Baseline (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.

  45. Mean QTcF Interval (Fridericia's Correction Formula, QTcF) - Change From Baseline (Day -1) at Day 14

    Time frame: Baseline (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.

  46. Mean QTcB Interval (Bazett's Correction Formula, QTcB) - Change From Baseline (Day -1) at Day 14

    Time frame: Baseline (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.

  47. Nature and Severity of Adverse Events (AEs) up to Day 21

    Time frame: On or after first drug administration up to end of study (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.

  48. Withdrawals Due to AEs up to Day 21

    Time frame: On or after first drug administration up to end of study (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.

Secondary outcomes

  1. Change in Frequency of Hot Flushes From Baseline (Day -1) at Days 7, 14 as Assessed by Skin Conductance

    Time frame: Baseline (day -1) and days 7, 14

    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.

  2. 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

    Time frame: Baseline (week -1) and Week 1 ,Week 2

    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.

  3. Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Severity of Hot Flushes as Measured by Twice Daily Paper Diary

    Time frame: Baseline (week -1) and weeks 1, Week 2

    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.

  4. Change From Baseline (Week -1) at Weeks 1, 2 in Average Daily Hot Flushes Severity Score as Measured by Twice Daily Paper Diary.

    Time frame: Baseline (week -1) and week 1 , 2

    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.

  5. Change in Frequency From Baseline (Day -1), at Days 7, 14 of Hot Flushes as Measured by Continuous Day Time Diary.

    Time frame: Baseline(day -1) and Day 7, 14

    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.

  6. Change From Baseline (Week -1) at Weeks 1, 2 in Night-time Awakenings (NTA) Secondary to Hot Flushes as Measured by Paper Diary

    Time frame: Baseline (week-1) and weeks 1 , 2

    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.

  7. Change From Baseline (Day-1) to Day 1 and Day 7 in Luteinizing Hormone (AUC0-8)

    Time frame: 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)

    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.

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Collaborators

  • Nerre Therapeutics Ltd.

Registry information

Official study title

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

Acronym: RELENT-1

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Aug 12, 2016
Registry last updated
Feb 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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