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A Study to Learn How the Study Treatment BAY1753011 Moves Into, Through and Out of the Body, How it Works, How Safe it is, and How it Affects the Body When Given Once as Tablet in Male and Female Participants With Reduced Kidney Function Compared to Matched Participants With Normal Kidney Function

Primary Purpose

Congestive Heart Failure, Renal Impairment

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Pecavaptan (BAY1753011)
Pecavaptan (BAY1753011)
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Congestive Heart Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Male or female White participants (women without childbearing potential) Aged from ≥18 years body mass index above or equal 18.5 kg/m2 and below or equal 36 kg/m2 at the first screening visit Participants with renal impairment: with an eGFR <90 mL/min/1.73 m^2 determined from serum creatinine 21-3 days prior to dosing using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation Age-, weight- and gender- matched control group Exclusion Criteria: An anatomical abnormality of the gut that could affect the retention times of the drug in the stomach/gut adversely Conditions or concomitant treatment that might adversely affect the gastric pH level Pancreatic dysfunction/insufficiency Febrile illness within 4 week prior to admission to study center Known hypersensitivity to the study drugs Known severe allergies, non-allergic drug reactions, or multiple drug allergies Participants with a medical disorder, condition or history of such that would impair the participant's ability to participate or complete this study in the opinion of the investigator or the Sponsor Concomitant treatment from 2 weeks before study drug administration until end of follow-up with drugs that may impact the PK of BAY 1753011:Strong and moderate inducers or inhibitors of CYP3A4Moderate and strong inhibitors of P-gp transport Probenecid and valproic acid Concomitant treatment with potassium-sparing diuretic (with the exception of mineralocorticoid- receptor antagonist [MRA]) that cannot be stopped prior to randomization and for the duration of the treatment period Although no clinical study data are available for BAY 1753011, drugs for the treatment of hyperphosphatemia such as sevelamer or lanthanum should not be given from 24 h before until 24 h after dosing, as they are known to bind many anionic drugs Acute renal failure Active nephritis Severe infection or any clinically significant illness within 4 weeks prior to dosing Impairment of any other major organ system other than the kidney Clinically relevant findings in the ECG such as a second- or third-degree atrioventricular (AV) block, prolongation of the QTc-interval over 480 msec Systolic blood pressure below 100 or above 160 mmHg Diastolic blood pressure below 50 or above 100 mmHg Heart rate below 50 or above 100 beats/ min

Sites / Locations

  • APEX GmbH
  • CRS Clinical-Research-Services Kiel GmbH

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Healthy

Mild renal impairment

Moderate renal impairment

Severe renal impairment

Arm Description

Age-, weight- and gender- matched control group of healthy volunteers received a single oral dose of 30 mg BAY1753011 tablet.

Subjects with mild renal impairment received a single oral dose of 30 mg BAY1753011 tablet.

Subjects with moderate renal impairment received a single oral dose of 30 mg BAY1753011 tablet.

Subjects with severe renal impairment received a single oral dose of 15 mg BAY1753011 tablet.

Outcomes

Primary Outcome Measures

Area under the concentration versus time curve from zero to infinity divided by dose of total BAY1753011 in plasma after single dose administration (AUC/D)
Dose-normalized AUC (AUC/D) of BAY1753011 was investigated as the dose for the severe renal impairment group was reduced to 15 mg.
Maximum observed drug concentration divided by dose of total BAY1753011 in plasma after single dose administration (Cmax/D)
Dose-normalized Cmax (Cmax/D) of BAY1753011 was investigated as the dose for the severe renal impairment group was reduced to 15 mg.
Area under the concentration versus time curve from zero to infinity divided by dose of unbound BAY1753011 in plasma after single dose administration (AUCu/D)
Dose-normalized AUCu (AUCu/D) of BAY1753011 was investigated as the dose for the severe renal impairment group was reduced to 15 mg.
Maximum observed drug concentration divided by dose of unbound BAY1753011 in plasma after single dose administration (Cmax,u/D)
Dose-normalized Cmax,u (Cmax,u/D) of BAY1753011 was investigated as the dose for the severe renal impairment group was reduced to 15 mg.

Secondary Outcome Measures

Number of participants with treatment-emergent adverse events

Full Information

First Posted
October 26, 2022
Last Updated
October 26, 2022
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT05599997
Brief Title
A Study to Learn How the Study Treatment BAY1753011 Moves Into, Through and Out of the Body, How it Works, How Safe it is, and How it Affects the Body When Given Once as Tablet in Male and Female Participants With Reduced Kidney Function Compared to Matched Participants With Normal Kidney Function
Official Title
Investigation of Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of a Single Oral Dose of 30 mg BAY 1753011 Given as IR Tablet in Male and Female Participants in a Multicenter, Non-randomized, Non-controlled, Non-blinded Study With Group Stratification in Participants With Renal Impairment and Control Group Matched for Age-, Gender-, and Weight
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
November 25, 2019 (Actual)
Primary Completion Date
January 22, 2021 (Actual)
Study Completion Date
May 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Researchers are looking for a better way to treat people with heart failure. Heart failure is a condition which occurs when the heart does not pump blood as well as it should leading to shortness of breath, tiredness, and ankle swelling. The study treatment BAY1753011 is under development to treat heart failure. It is thought to reduce the action of a hormone called vasopressin that is naturally produced in the body. People with heart failure often have elevated levels of vasopressin. This is known to result in worsening of the heart failure condition. People with heart failure often also have reduced kidney functions. As kidneys play a role in removal of drugs from the body, reduced kidney function may result in higher blood levels of BAY1753011. The main purpose of this study was to learn how BAY1753011 moved into, through and out of the body in participants with different degrees of reduced kidney function compared to matched participants (age, gender, and weight) with normal kidney function. To answer this, the researchers compared: the (average) total level of BAY1753011 in the blood (also called AUC) the (average) highest level of BAY1753011 in the blood (also called Cmax) between the different groups with reduced kidney function (mild/moderate/severe) and the control group (normal kidney function). In addition, the researchers wanted to know how safe BAY1753011 was and the degree to which overt medical problems caused by it could be tolerated (also called tolerability) by the different groups of participants. These medical problems are also known as "adverse events". Doctors keep track of all medical problems that happen in studies, even if they do not think they might be related to the study treatments. All participants took a single dose of BAY1753011 in tablet form by mouth. Each participant was in the study for approximately 3 to 4 weeks, including an in-house phase of 5 days and 4 nights with one treatment day. During the study, the doctors and their study team: did physical examinations checked vital signs such as blood pressure, heart rate, body temperature and number of breaths within a minute (respiratory rate) examined heart health using electrocardiogram (ECG) took blood and urine samples counted the number of toilet visits during the night

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congestive Heart Failure, Renal Impairment

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Healthy
Arm Type
Experimental
Arm Description
Age-, weight- and gender- matched control group of healthy volunteers received a single oral dose of 30 mg BAY1753011 tablet.
Arm Title
Mild renal impairment
Arm Type
Experimental
Arm Description
Subjects with mild renal impairment received a single oral dose of 30 mg BAY1753011 tablet.
Arm Title
Moderate renal impairment
Arm Type
Experimental
Arm Description
Subjects with moderate renal impairment received a single oral dose of 30 mg BAY1753011 tablet.
Arm Title
Severe renal impairment
Arm Type
Experimental
Arm Description
Subjects with severe renal impairment received a single oral dose of 15 mg BAY1753011 tablet.
Intervention Type
Drug
Intervention Name(s)
Pecavaptan (BAY1753011)
Intervention Description
30 mg, immediate release tablet, single dose, oral
Intervention Type
Drug
Intervention Name(s)
Pecavaptan (BAY1753011)
Intervention Description
15 mg, immediate release tablet, single dose, oral
Primary Outcome Measure Information:
Title
Area under the concentration versus time curve from zero to infinity divided by dose of total BAY1753011 in plasma after single dose administration (AUC/D)
Description
Dose-normalized AUC (AUC/D) of BAY1753011 was investigated as the dose for the severe renal impairment group was reduced to 15 mg.
Time Frame
From pre-dose until 144 hours post dose
Title
Maximum observed drug concentration divided by dose of total BAY1753011 in plasma after single dose administration (Cmax/D)
Description
Dose-normalized Cmax (Cmax/D) of BAY1753011 was investigated as the dose for the severe renal impairment group was reduced to 15 mg.
Time Frame
From pre-dose until 144 hours post dose
Title
Area under the concentration versus time curve from zero to infinity divided by dose of unbound BAY1753011 in plasma after single dose administration (AUCu/D)
Description
Dose-normalized AUCu (AUCu/D) of BAY1753011 was investigated as the dose for the severe renal impairment group was reduced to 15 mg.
Time Frame
From pre-dose until 144 hours post dose
Title
Maximum observed drug concentration divided by dose of unbound BAY1753011 in plasma after single dose administration (Cmax,u/D)
Description
Dose-normalized Cmax,u (Cmax,u/D) of BAY1753011 was investigated as the dose for the severe renal impairment group was reduced to 15 mg.
Time Frame
From pre-dose until 144 hours post dose
Secondary Outcome Measure Information:
Title
Number of participants with treatment-emergent adverse events
Time Frame
After first application of study medication up to 10 days after the study medication

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female White participants (women without childbearing potential) Aged from ≥18 years body mass index above or equal 18.5 kg/m2 and below or equal 36 kg/m2 at the first screening visit Participants with renal impairment: with an eGFR <90 mL/min/1.73 m^2 determined from serum creatinine 21-3 days prior to dosing using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation Age-, weight- and gender- matched control group Exclusion Criteria: An anatomical abnormality of the gut that could affect the retention times of the drug in the stomach/gut adversely Conditions or concomitant treatment that might adversely affect the gastric pH level Pancreatic dysfunction/insufficiency Febrile illness within 4 week prior to admission to study center Known hypersensitivity to the study drugs Known severe allergies, non-allergic drug reactions, or multiple drug allergies Participants with a medical disorder, condition or history of such that would impair the participant's ability to participate or complete this study in the opinion of the investigator or the Sponsor Concomitant treatment from 2 weeks before study drug administration until end of follow-up with drugs that may impact the PK of BAY 1753011:Strong and moderate inducers or inhibitors of CYP3A4Moderate and strong inhibitors of P-gp transport Probenecid and valproic acid Concomitant treatment with potassium-sparing diuretic (with the exception of mineralocorticoid- receptor antagonist [MRA]) that cannot be stopped prior to randomization and for the duration of the treatment period Although no clinical study data are available for BAY 1753011, drugs for the treatment of hyperphosphatemia such as sevelamer or lanthanum should not be given from 24 h before until 24 h after dosing, as they are known to bind many anionic drugs Acute renal failure Active nephritis Severe infection or any clinically significant illness within 4 weeks prior to dosing Impairment of any other major organ system other than the kidney Clinically relevant findings in the ECG such as a second- or third-degree atrioventricular (AV) block, prolongation of the QTc-interval over 480 msec Systolic blood pressure below 100 or above 160 mmHg Diastolic blood pressure below 50 or above 100 mmHg Heart rate below 50 or above 100 beats/ min
Facility Information:
Facility Name
APEX GmbH
City
München
State/Province
Bayern
ZIP/Postal Code
81241
Country
Germany
Facility Name
CRS Clinical-Research-Services Kiel GmbH
City
Kiel
State/Province
Schleswig-Holstein
ZIP/Postal Code
24105
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
Links:
URL
https://clinicaltrials.bayer.com/
Description
Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Learn more about this trial

A Study to Learn How the Study Treatment BAY1753011 Moves Into, Through and Out of the Body, How it Works, How Safe it is, and How it Affects the Body When Given Once as Tablet in Male and Female Participants With Reduced Kidney Function Compared to Matched Participants With Normal Kidney Function

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