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

• Sponsor: Bayer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04322253
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arms: 3
• Actual Duration (Months): 15.8
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Pharmacology, Clinical	Drug: Neladenoson bialanate (BAY 1067197)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: Aug 24, 2017
• Actual Primary Completion Date: Aug 22, 2018
• Actual Study Completion Date: Dec 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
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
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

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

3. AUCu for BAY 84-3174 [Pre-dose up to 49 days after study drug administration]

   AUC of unbound drug after single dose administration

4. 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

5. 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

6. Cmax,u for BAY 84-3174 [Pre-dose up to 49 days after study drug administration]

   Cmax of unbound drug after single dose administration

7. 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

Secondary Outcome Measures

1. Number of subjects with treatment-emergent adverse events (TEAEs) [Up to 49 days after study drug administration]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CRS Clinical-Research-Services Kiel GmbH	Kiel	Schleswig-Holstein	Germany	24105

Sponsors and Collaborators

• Bayer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT04322253
• Other Study ID Numbers: 15139; 2017-000482-74
• First Posted: Mar 26, 2020
• Last Update Posted: Mar 26, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Mar 26, 2020