Pharmacology, Clinical
Conditions
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
Interventions
10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| fu for BAY 84-3174 | At 4 hours after dosing | Fraction of free (unbound) drug in plasma or serum after single dose administration |
| Cmax for BAY 84-3174 | Pre-dose up to approximately 6 weeks after dosing | Maximum observed drug concentration in measured matrix after single dose administration |
| AUC for BAY 84-3174 | Pre-dose up to approximately 6 weeks after dosing | Area under the concentration vs. time curve from zero to infinity after single dose administration |
| Cmax,norm for BAY 84-3174 | Pre-dose up to approximately 6 weeks after dosing | Cmax divided by dose per body weight after single dose administration |
| AUCnorm for BAY 84-3174 | Pre-dose up to approximately 6 weeks after dosing | AUC divided by dose per body weight after single dose administration |
| Cmax,u for BAY 84-3174 | Pre-dose up to approximately 6 weeks after dosing | Cmax of unbound drug after single dose administration |
| AUCu for BAY 84-3174 | Pre-dose up to approximately 6 weeks after dosing | AUC of unbound drug after single dose administration |
Secondary
| Measure | Time frame |
|---|---|
| Number of subjects with treatment-emergent adverse events (TEAEs) | Up to approximately 6 weeks after dosing |
Countries
Germany
Outcome results
None listed