Back to resultsStudy on the Safety of Neladenoson Bialanate, How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Dug Given as a Single Oral Dose of 10 mg Immediate Release Tablet in Participants With Renal Impairment and Healthy Participants Matched for Age-, Gender-, and Weight
Primary Purpose
Pharmacology, Clinical
Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Neladenoson bialanate (BAY 1067197)
Sponsored by
About this trial
This is an interventional basic science trial for Pharmacology, Clinical
Eligibility Criteria
Inclusion Criteria:
All subjects:
- Male or female White subjects (women without childbearing potential), aged 18 to 79 years (inclusive), body mass index 18 to 34 kg/m² (both inclusive)
Subjects with renal impairment:
- Estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m² determined from serum creatinine 2-14 days prior to dosing using the Modification of Diet in Renal Disease equation
- Stable renal disease, i.e. a serum creatinine value determined at least 3 months before the pre-study visit should not vary by more than 25% from the serum creatinine value determined at the pre-study visit.
Healthy subjects:
- Age-, weight- and gender matched healthy subjects
Exclusion Criteria:
- An anatomical abnormality of the gut (e.g. gut surgery, continent ileostomy) that could affect the retention times of the drug in the stomach/gut adversely
- Gastric vagotomy or other condition that might adversely affect the gastric pH level
- Pancreatic dysfunction/insufficiency
- Febrile illness within 1 week prior to admission to study center
- Use of the following co-medications
From 2 weeks before administration until end of follow-up:
- Cytochrome P450 (CYP)3A4 inhibitors (Of note: grapefruit is a strong CYP3A4 inhibitor)
- CYP3A4 inducers
- CYP2C8 inhibitors (Of note: clopidogrel is a strong CYP2C8 inhibitor)
- Theophylline
On the day of dosing with neladenoson bialanate:
- Drugs that undergo significant systemic metabolism over gut wall uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) substrates (e.g. irinotecan)
- Major breast cancer resistance protein (BCRP) substrates
- Regular daily consumption of more than 1 L - Plasmapheresis within 4 weeks before study drug administration
- Therapies (e.g. physiotherapy, acupuncture, etc.) within 1 week before study drug administration
- History of relevant and not cured cardiac rhythm disorders (i.e. Wolff-Parkinson-White syndrome, intermittent second- or third-degree AV block)
- Positive urine drug screening
- Subjects tested to be positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus
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
Neladenoson bialanate, mild renal impairment
Neladenoson bialanate, moderate renal impairment
Neladenoson bialanate, severe renal impairment
Neladenoson bialanate, control group
Arm Description
Subjects with eGFR ≥60 - <90 mL/min/1.73 received a single immediate-release (IR) tablet dose of 10 mg of neladenoson bialanate in the fasted state
Subjects with eGFR ≥30 - <60 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state
Subjects with eGFR <30 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state
Healthy subjects matched for age, gender and body weight received a single IR tablet dose of 10 mg neladenoson bialanate in the fasted state
Outcomes
Primary Outcome Measures
Cmax for BAY 84-3174
Maximum observed drug concentration in measured matrix after single dose administration
AUC for BAY 84-3174
Area under the concentration vs. time curve from zero to infinity after single dose administration
Cmax,norm for BAY 84-3174
Cmax divided by dose per body weight after single dose administration
AUCnorm for BAY 84-3174
AUC divided by dose per body weight after single dose administration
Cmax,u for BAY 84-3174
Cmax of unbound drug after single dose administration
AUCu for BAY 84-3174
AUC of unbound drug after single dose administration
fu for BAY 84-3174
Fraction of free (unbound) drug in plasma or serum after single dose administration
Secondary Outcome Measures
Number of subjects with treatment-emergent adverse events (TEAEs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04320771
Brief Title
Study on the Safety of Neladenoson Bialanate, How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Dug Given as a Single Oral Dose of 10 mg Immediate Release Tablet in Participants With Renal Impairment and Healthy Participants Matched for Age-, Gender-, and Weight
Official Title
Investigation of Pharmacokinetics, Safety and Tolerability of Neladenoson Bialanate in Male and Female Subjects With Renal Impairment and in Age-, Gender-, and Weight-matched Healthy Subjects Following a Single Oral Dose of 10 mg Neladenoson Bialanate Given as IR Tablet in a Single-center, Nonrandomized, Non-controlled, Non-blinded, Study With Group Stratification
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
Termination of the development project for Neladenoson bialanate
Study Start Date
November 2, 2017 (Actual)
Primary Completion Date
August 8, 2018 (Actual)
Study Completion Date
December 17, 2018 (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
Neladenoson bialanate is currently under clinical development for a condition in which the heart has trouble pumping blood through the body (chronic heart failure). Renal impairment which co-occurs in patients with heart failure is a common condition in which the kidneys are not filtering the blood as well as they should. The goal of the study is to learn more about the safety of neladenoson bialanate, how it is tolerated and the way the body absorbs, distributes and excretes the study dug given as a single oral dose of 10 mg immediate release tablet in participants with renal impairment and healthy participants matched for age-, gender-, and weight
Detailed Description
Study was originally designed with 4 arms (normal renal function, mild, moderate, and severe renal impairment), however as the study was prematurely terminated, there was no participant with normal renal function enrolled
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pharmacology, Clinical
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Neladenoson bialanate, mild renal impairment
Arm Type
Experimental
Arm Description
Subjects with eGFR ≥60 - <90 mL/min/1.73 received a single immediate-release (IR) tablet dose of 10 mg of neladenoson bialanate in the fasted state
Arm Title
Neladenoson bialanate, moderate renal impairment
Arm Type
Experimental
Arm Description
Subjects with eGFR ≥30 - <60 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state
Arm Title
Neladenoson bialanate, severe renal impairment
Arm Type
Experimental
Arm Description
Subjects with eGFR <30 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state
Arm Title
Neladenoson bialanate, control group
Arm Type
Experimental
Arm Description
Healthy subjects matched for age, gender and body weight received a single IR tablet dose of 10 mg neladenoson bialanate in the fasted state
Intervention Type
Drug
Intervention Name(s)
Neladenoson bialanate (BAY 1067197)
Intervention Description
10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174
Primary Outcome Measure Information:
Title
Cmax for BAY 84-3174
Description
Maximum observed drug concentration in measured matrix after single dose administration
Time Frame
Pre-dose up to approximately 6 weeks after dosing
Title
AUC for BAY 84-3174
Description
Area under the concentration vs. time curve from zero to infinity after single dose administration
Time Frame
Pre-dose up to approximately 6 weeks after dosing
Title
Cmax,norm for BAY 84-3174
Description
Cmax divided by dose per body weight after single dose administration
Time Frame
Pre-dose up to approximately 6 weeks after dosing
Title
AUCnorm for BAY 84-3174
Description
AUC divided by dose per body weight after single dose administration
Time Frame
Pre-dose up to approximately 6 weeks after dosing
Title
Cmax,u for BAY 84-3174
Description
Cmax of unbound drug after single dose administration
Time Frame
Pre-dose up to approximately 6 weeks after dosing
Title
AUCu for BAY 84-3174
Description
AUC of unbound drug after single dose administration
Time Frame
Pre-dose up to approximately 6 weeks after dosing
Title
fu for BAY 84-3174
Description
Fraction of free (unbound) drug in plasma or serum after single dose administration
Time Frame
At 4 hours after dosing
Secondary Outcome Measure Information:
Title
Number of subjects with treatment-emergent adverse events (TEAEs)
Time Frame
Up to approximately 6 weeks after dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
All subjects:
Male or female White subjects (women without childbearing potential), aged 18 to 79 years (inclusive), body mass index 18 to 34 kg/m² (both inclusive)
Subjects with renal impairment:
Estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m² determined from serum creatinine 2-14 days prior to dosing using the Modification of Diet in Renal Disease equation
Stable renal disease, i.e. a serum creatinine value determined at least 3 months before the pre-study visit should not vary by more than 25% from the serum creatinine value determined at the pre-study visit.
Healthy subjects:
Age-, weight- and gender matched healthy subjects
Exclusion Criteria:
An anatomical abnormality of the gut (e.g. gut surgery, continent ileostomy) that could affect the retention times of the drug in the stomach/gut adversely
Gastric vagotomy or other condition that might adversely affect the gastric pH level
Pancreatic dysfunction/insufficiency
Febrile illness within 1 week prior to admission to study center
Use of the following co-medications
From 2 weeks before administration until end of follow-up:
Cytochrome P450 (CYP)3A4 inhibitors (Of note: grapefruit is a strong CYP3A4 inhibitor)
CYP3A4 inducers
CYP2C8 inhibitors (Of note: clopidogrel is a strong CYP2C8 inhibitor)
Theophylline
On the day of dosing with neladenoson bialanate:
Drugs that undergo significant systemic metabolism over gut wall uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) substrates (e.g. irinotecan)
Major breast cancer resistance protein (BCRP) substrates
Regular daily consumption of more than 1 L - Plasmapheresis within 4 weeks before study drug administration
Therapies (e.g. physiotherapy, acupuncture, etc.) within 1 week before study drug administration
History of relevant and not cured cardiac rhythm disorders (i.e. Wolff-Parkinson-White syndrome, intermittent second- or third-degree AV block)
Positive urine drug screening
Subjects tested to be positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus
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
Undecided
IPD Sharing Plan Description
Availability of this study's data will 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.
Links:
URL
http://clinicaltrials.bayer.com/
Description
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Learn more about this trial
Study on the Safety of Neladenoson Bialanate, How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Dug Given as a Single Oral Dose of 10 mg Immediate Release Tablet in Participants With Renal Impairment and Healthy Participants Matched for Age-, Gender-, and Weight
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