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
About this trial
This is an interventional basic science trial for Pharmacology, Clinical
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
Sites / Locations
- APEX GmbH
- CRS Clinical-Research-Services Kiel GmbH
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Neladenoson bialanate, mild renal impairment
Neladenoson bialanate, moderate renal impairment
Neladenoson bialanate, severe renal impairment
Neladenoson bialanate, control group
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
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
Subjects with eGFR <30 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state
Healthy subjects matched for age, gender and body weight received a single IR tablet dose of 10 mg neladenoson bialanate in the fasted state