Termination of the development project for Neladenoson bialanate

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

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

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

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.