Clinical trial NCT04322253: 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 in Participants With Liver Impairment and Healthy Participants Matched for Age-, Gender-, and Weight
Official title: Investigation of the Pharmacokinetics, Safety, and Tolerability of Neladenoson Bialanate in Subjects With Hepatic Impairment (Classified as Child Pugh A and B) and in Age-, Weight-, and Gender-matched Healthy Subjects, Following a Single Oral Dose in a Single-center, Non-randomized, Non-controlled, Non-blinded Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pharmacology, Clinical
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-03-26
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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).

Primary outcomes:
measure: fu for BAY 84-3174
timeFrame: At 4 hours after study drug administration
measure: AUC for BAY 84-3174
timeFrame: Pre-dose up to 49 days after study drug administration
measure: AUCu for BAY 84-3174
timeFrame: Pre-dose up to 49 days after study drug administration
measure: AUCnorm for BAY 84-3174
timeFrame: Pre-dose up to 49 days after study drug administration
measure: Cmax for BAY 84-3174
timeFrame: Pre-dose up to 49 days after study drug administration
measure: Cmax,u for BAY 84-3174
timeFrame: Pre-dose up to 49 days after study drug administration
measure: Cmax,norm for BAY 84-3174
timeFrame: Pre-dose up to 49 days after study drug administration
Secondary outcomes:
measure: Number of subjects with treatment-emergent adverse events (TEAEs)
timeFrame: Up to 49 days after study drug administration
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: CRS Clinical-Research-Services Kiel GmbH
state: Schleswig-Holstein
Study officials:
References: