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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Pharmacology, Clinical

Intervention / Treatment
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* Drug: Neladenoson bialanate (BAY 1067197)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neladenoson bialanate, mild renal impairment<br>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 | Drug: Neladenoson bialanate (BAY 1067197)<br>* 10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174<br>|
| Experimental: Neladenoson bialanate, moderate renal impairment<br>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 | Drug: Neladenoson bialanate (BAY 1067197)<br>* 10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174<br>|
| Experimental: Neladenoson bialanate, severe renal impairment<br>Subjects with eGFR <30 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state | Drug: Neladenoson bialanate (BAY 1067197)<br>* 10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174<br>|
| Experimental: Neladenoson bialanate, control group<br>Healthy subjects matched for age, gender and body weight received a single IR tablet dose of 10 mg neladenoson bialanate in the fasted state | Drug: Neladenoson bialanate (BAY 1067197)<br>* 10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for BAY 84-3174 | Maximum observed drug concentration in measured matrix after single dose administration | Pre-dose up to approximately 6 weeks after dosing | 
| AUC for BAY 84-3174 | Area under the concentration vs. time curve from zero to infinity after single dose administration | Pre-dose up to approximately 6 weeks after dosing | 
| Cmax,norm for BAY 84-3174 | Cmax divided by dose per body weight after single dose administration | Pre-dose up to approximately 6 weeks after dosing | 
| AUCnorm for BAY 84-3174 | AUC divided by dose per body weight after single dose administration | Pre-dose up to approximately 6 weeks after dosing | 
| Cmax,u for BAY 84-3174 | Cmax of unbound drug after single dose administration | Pre-dose up to approximately 6 weeks after dosing | 
| AUCu for BAY 84-3174 | AUC of unbound drug after single dose administration | Pre-dose up to approximately 6 weeks after dosing | 
| fu for BAY 84-3174 | Fraction of free (unbound) drug in plasma or serum after single dose administration | At 4 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with treatment-emergent adverse events (TEAEs) |  | Up to approximately 6 weeks after dosing |