A Study to Learn How the Study Treatment Asundexian Moves Into, Through and Out of the Body, How it Works, How Safe it is, and How it Affects the Body in Participants With Mild or Moderate Reduction of Liver Function Compared to Participants With Normal Liver Function

This is an interventional basic science trial for Prevention of Thromboembolic Events Read More

Inclusion Criteria:

All participants:

• Participant must be more than 18 years of age inclusive, at the time of signing the informed consent.
• Body mass index (BMI) within the range 18.0 and 35.0 kg2 (inclusive).
• Race: White (Note: Clinical Data Interchange Standards Consortium definition of White: Denotes a person with European, Middle Eastern, or North African ancestral origin who identifies, or is identified, as White [FDA]).
• Male and/or female participants.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Participants With Hepatic Impairment:

• Participants with documented liver cirrhosis confirmed by histopathology (e.g., previous liver biopsy), laparoscopy, or by ultrasound, or fibroscan.
• Participants with hepatic impairment (Child Pugh A or B).
• Participants with stable liver disease in the last 2 months prior to screening.

Participants of age-, weight-, and gender-matched group :

• Participants with normal hepatic function.
• Mean age and body weight in the control group and in the two groups with hepatic impairment (Child Pugh A and B) should not vary by more than ±10 years and ±10 kg.
• Gender-matched (the gender distribution in the control group should be as similar as possible to the groups with hepatic impairment).

Exclusion Criteria:

All participants:

• Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study intervention will not be normal except for hepatic impairment in participants with hepatic impairment.
• Known severe allergies e.g., allergies to more than 3 allergens, allergies affecting the lower respiratory tract - allergic asthma, allergies requiring therapy with corticosteroids (except for topical use), urticaria or significant non-allergic drug reactions.
• History of known or suspected malignant tumors except completely resected basal cell cancer of the skin (excision >6 months before screening).
• Tendency for vasovagal reactions (e.g. after venipuncture) or history of syncope after venipuncture.
• Participants with untreated, unstable thyroid disorders as evidenced by clinically relevant deviation from normal ranges of thyroid stimulating hormone (TSH) and signs/symptoms of a thyroid disorder at screening.

Participants With Hepatic Impairment:

• Evidence of hepatic encephalopathy related to chronic liver disease > grade 2
• Congestive heart failure of New York Heart Association grade III or IV.
• Participants with percutaneous transluminal coronary angioplasty or coronary artery bypass graft less than 6 months prior to administration of study intervention.
• History of conspicuous bleeding within the past 3 months.
• Severe ascites of more than 6 L (estimated by ultrasound).
• Participants with primary and secondary biliary cirrhosis.
• Participants with sclerosing cholangitis.
• Clinically relevant findings in the electrocardiogram (ECG) such as a second- or third-degree atrioventricular (AV) block or a prolongation of the QTcF-interval (Fridericia's correction) over 480 ms (males and females).
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in conjunction with gamma glutamyl transpeptidase (GGT) equal or above 4 times the upper limit of normal (ULN) (an isolated elevation of GGT above 4 times ULN will not exclude the participant).
• Serum albumin below 2 g/dL.
• Prothrombin time (Quick test) below 40%
• Participants with diabetes mellitus with a glycated hemoglobin (HbA1c) above 10%.
• Chronic kidney disease with an estimated glomerular filtration rate (eGFR) equal or below 40 mL/min/1.73 m^2 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).

Participants of age-, weight-, and gender-matched group:

• A history of relevant diseases with the exception of mild, well controlled hypertension, dyslipoproteinemia and thyroid disorders.
• History of Morbus Meulengracht (Gilbert´s syndrome) and impairment of bile secretion/flow (cholestasis, also history of it).
• Relevant history of liver disorders which could increase the individual risk for the participant.
• Hepatic impairment or active liver disease, which may include unexplained persistent transaminase elevations.
• Renal impairment with an eGFR below age-appropriate values (CKD-EPI).
• Clinically relevant findings in the ECG, such as relevant arrhythmic or conduction disturbances (e.g., AV block grad II or III, QRS complex ≥120 ms), QTcF interval (Fridericia's correction) >450 ms (males) or >470 ms (females) at screening.
• Liver markers (e.g., ALT, AST, alkaline phosphatase, gamma glutamyl transpeptidase or total bilirubin) above 1.5 x ULN at screening.
• HbA1c above 6.7%.