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

NCT04320771 | Terminated Phase 1

• 2 other identifiers: 151382017-000795-28
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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

Conditions

Pharmacology, Clinical

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• 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

• Cmax,u for BAY 84-3174

  Cmax of unbound drug after single dose administration

  Pre-dose up to approximately 6 weeks after dosing

• AUCu for BAY 84-3174

  AUC of unbound drug after single dose administration

  Pre-dose up to approximately 6 weeks after dosing

• fu for BAY 84-3174

  Fraction of free (unbound) drug in plasma or serum after single dose administration

  At 4 hours after dosing

Secondary Outcomes (1)

• Number of subjects with treatment-emergent adverse events (TEAEs)

  Up to approximately 6 weeks after dosing

Study Arms (4)

Neladenoson bialanate, mild renal impairment

EXPERIMENTAL

Subjects with eGFR ≥60 - \<90 mL/min/1.73 received a single immediate-release (IR) tablet dose of 10 mg of neladenoson bialanate in the fasted state

Drug: Neladenoson bialanate (BAY 1067197)

Neladenoson bialanate, moderate renal impairment

EXPERIMENTAL

Subjects with eGFR ≥30 - \<60 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state

Drug: Neladenoson bialanate (BAY 1067197)

Neladenoson bialanate, severe renal impairment

EXPERIMENTAL

Subjects with eGFR \<30 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state

Drug: Neladenoson bialanate (BAY 1067197)

Neladenoson bialanate, control group

EXPERIMENTAL

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)

Interventions

Neladenoson bialanate (BAY 1067197) DRUG

10 mg as a single IR tablet dose. Active metabolite: BAY 84-3174

Neladenoson bialanate, control group; Neladenoson bialanate, mild renal impairment; Neladenoson bialanate, moderate renal impairment; Neladenoson bialanate, severe renal impairment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (2)

APEX GmbH

München, Bavaria, 81241, Germany

Location

CRS Clinical-Research-Services Kiel GmbH

Kiel, Schleswig-Holstein, 24105, Germany

Location

Related Links

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

MeSH Terms

Interventions

neladenoson bialanate

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 25, 2020
• Study Start: November 2, 2017
• Primary Completion: August 8, 2018
• Study Completion: December 17, 2018
• Last Updated: March 26, 2020

Record last verified: 2020-03

Locations

DE (2)