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). Liver impairment is a condition in which the liver is not working 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 neladenoson bialanate in participants with liver impairment and healthy participants matched for age-, gender-, and weight
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 and female Caucasian subjects between 18 and 79 years of age (both inclusive) with a body mass index above/equal 18.0 and below/equal 34.0 kg/m² Subjects with hepatic impairment * Subjects with documented liver cirrhosis confirmed by histopathology, e.g., previous liver biopsy, laparoscopy, ultrasound, or fibroscan * Subjects with hepatic impairment as per Child Pugh system * Subjects with stable liver disease during the last 2 months Healthy subjects * Healthy subjects with mean age and body weight not varying by more than ±10 years and ±10 kg from the groups of subjects with mild and moderate hepatic impairment, respectively.
Exclusion criteria
* Medical history of continent ileostomy. * Febrile illness within 1 week prior to admission to study center. * Known hypersensitivity to the study drug (active substances or excipients of the preparation). * Subjects with diagnosed malignancy within the past 5 years. * Use of any systemic or topical medicine or substances which oppose the study objectives or which might influence them, in particular: Starting from screening on, but minimum from 2 weeks before the study drug administration until the follow-up visit: * CYP3A4 inducers * CYP3A4 inhibitors * Potent CYP2C8 inhibitors * Major uridine diphosphate-glucuronosyltransferase isoenzyme 1A1 (UGT1A1) substrate (irinotecan) On the day of administration of neladenoson bialanate: * Major breast cancer resistance protein (BCRP) substrates * Regular daily consumption of more than 500 mL of usual beer or the equivalent quantity of of more than 2 units of alcohol in another form - Intake of ethanol containing food and beverages from 48 h prior to admission to the study center until 96 h after study drug administration, afterwards not more than 2 units of alcohol per day until follow-up examination. * Intake of food and beverages containing grapefruit or pomelo from 14 days prior to study drug administration up to the last time point of PK sampling. * Therapies (e.g. physiotherapy, acupuncture, etc.) within 1 week before study drug administration. * Positive urine drug screening. * Positive results for human immune deficiency - Abnormal (clinically significant) thyroid stimulating hormone (TSH).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax,norm for BAY 84-3174 | Pre-dose up to 49 days after study drug administration | Cmax divided by dose per body weight after single dose administration |
| fu for BAY 84-3174 | At 4 hours after study drug administration | Fraction of free (unbound) drug in plasma or serum after single dose administration |
| AUC for BAY 84-3174 | Pre-dose up to 49 days after study drug administration | Area under the concentration vs. time curve from zero to infinity after single dose administration |
| AUCu for BAY 84-3174 | Pre-dose up to 49 days after study drug administration | AUC of unbound drug after single dose administration |
| AUCnorm for BAY 84-3174 | Pre-dose up to 49 days after study drug administration | AUC divided by dose per body weight after single dose administration |
| Cmax for BAY 84-3174 | Pre-dose up to 49 days after study drug administration | Maximum observed drug concentration in measured matrix after single dose administration |
| Cmax,u for BAY 84-3174 | Pre-dose up to 49 days after study drug administration | Cmax of unbound drug after single dose administration |
Secondary
| Measure | Time frame |
|---|---|
| Number of subjects with treatment-emergent adverse events (TEAEs) | Up to 49 days after study drug administration |
Countries
Germany
Outcome results
None listed