Clinical trial NCT04320771: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pharmacology, Clinical
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-03-25
Enrollment: 18
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). 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

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Cmax for BAY 84-3174
timeFrame: Pre-dose up to approximately 6 weeks after dosing
measure: AUC for BAY 84-3174
timeFrame: Pre-dose up to approximately 6 weeks after dosing
measure: Cmax,norm for BAY 84-3174
timeFrame: Pre-dose up to approximately 6 weeks after dosing
measure: AUCnorm for BAY 84-3174
timeFrame: Pre-dose up to approximately 6 weeks after dosing
measure: Cmax,u for BAY 84-3174
timeFrame: Pre-dose up to approximately 6 weeks after dosing
measure: AUCu for BAY 84-3174
timeFrame: Pre-dose up to approximately 6 weeks after dosing
measure: fu for BAY 84-3174
timeFrame: At 4 hours after dosing
Secondary outcomes:
measure: Number of subjects with treatment-emergent adverse events (TEAEs)
timeFrame: Up to approximately 6 weeks after dosing
Other outcomes:
Locations:
city: München
country: Germany
facility: APEX GmbH
state: Bayern
city: Kiel
country: Germany
facility: CRS Clinical-Research-Services Kiel GmbH
state: Schleswig-Holstein
Study officials:
References: