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

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

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

Study Overview

• Status: Terminated
• Conditions: Pharmacology, Clinical
• Intervention / Treatment: Drug: Neladenoson bialanate (BAY 1067197)

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • CRS Clinical-Research-Services Kiel GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neladenoson bialanate, control group; 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); 10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174
Experimental: Neladenoson bialanate, mild hepatic impairment; Subjects with Child Pugh score 5 or 6 received a single immediate-release (IR) tablet dose of 10 mg neladenoson bialanate in the fasted state	Drug: Neladenoson bialanate (BAY 1067197); 10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174
Experimental: Neladenoson bialanate, moderate hepatic impairment; Subjects with Child Pugh score 7-9 received a single IR tablet dose of 10 mg neladenoson bialanate in the fasted state	Drug: Neladenoson bialanate (BAY 1067197); 10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fu for BAY 84-3174	Fraction of free (unbound) drug in plasma or serum after single dose administration	At 4 hours after study drug administration
AUC for BAY 84-3174	Area under the concentration vs. time curve from zero to infinity after single dose administration	Pre-dose up to 49 days after study drug administration
AUCu for BAY 84-3174	AUC of unbound drug after single dose administration	Pre-dose up to 49 days after study drug administration
AUCnorm for BAY 84-3174	AUC divided by dose per body weight after single dose administration	Pre-dose up to 49 days after study drug administration
Cmax for BAY 84-3174	Maximum observed drug concentration in measured matrix after single dose administration	Pre-dose up to 49 days after study drug administration
Cmax,u for BAY 84-3174	Cmax of unbound drug after single dose administration	Pre-dose up to 49 days after study drug administration
Cmax,norm for BAY 84-3174	Cmax divided by dose per body weight after single dose administration	Pre-dose up to 49 days after study drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with treatment-emergent adverse events (TEAEs)	Up to 49 days after study drug administration

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2017
• Primary Completion (Actual): August 22, 2018
• Study Completion (Actual): December 17, 2018

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 15139; 2017-000482-74 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No