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 of 10 mg Immediate Release Tablet in Participants With Renal Impairment and Healthy Participants Matched for Age-, Gender-, and Weight

Pharmacology, Clinical Clinical Trial

Official title:

Investigation of Pharmacokinetics, Safety and Tolerability of Neladenoson Bialanate in Male and Female Subjects With Renal Impairment and in Age-, Gender-, and Weight-matched Healthy Subjects Following a Single Oral Dose of 10 mg Neladenoson Bialanate Given as IR Tablet in a Single-center, Nonrandomized, Non-controlled, Non-blinded, Study With Group Stratification

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04320771
• Other study ID #: 15138
• Secondary ID: 2017-000795-28
• Status: Terminated
• Phase: Phase 1
• Start date: November 2, 2017
• Est. completion date: December 17, 2018

Study information

• Verified date: March 2020
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: December 17, 2018
• Est. primary completion date: August 8, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Pharmacology, Clinical
• Renal Insufficiency

Intervention

Drug:
• Neladenoson bialanate (BAY 1067197)
10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174

Locations

Country	Name	City	State
Germany	CRS Clinical-Research-Services Kiel GmbH	Kiel	Schleswig-Holstein
Germany	APEX GmbH	München	Bayern

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax for BAY 84-3174	Maximum observed drug concentration in measured matrix after single dose administration	Pre-dose up to approximately 6 weeks after dosing
Primary	AUC for BAY 84-3174	Area under the concentration vs. time curve from zero to infinity after single dose administration	Pre-dose up to approximately 6 weeks after dosing
Primary	Cmax,norm for BAY 84-3174	Cmax divided by dose per body weight after single dose administration	Pre-dose up to approximately 6 weeks after dosing
Primary	AUCnorm for BAY 84-3174	AUC divided by dose per body weight after single dose administration	Pre-dose up to approximately 6 weeks after dosing
Primary	Cmax,u for BAY 84-3174	Cmax of unbound drug after single dose administration	Pre-dose up to approximately 6 weeks after dosing
Primary	AUCu for BAY 84-3174	AUC of unbound drug after single dose administration	Pre-dose up to approximately 6 weeks after dosing
Primary	fu for BAY 84-3174	Fraction of free (unbound) drug in plasma or serum after single dose administration	At 4 hours after dosing
Secondary	Number of subjects with treatment-emergent adverse events (TEAEs)		Up to approximately 6 weeks after dosing

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