Inclusion Criteria:
- Body weight of at least 50 kg and body mass index within the range of 18 and 35 kg/m^2 (inclusive).
- Female of non-childbearing potential or male
Participants with Moderate Hepatic Impairment and Moderate Renal Impairment only (Cohort 1)
- An estimated glomerular filtration rate (eGFR) in the range of 30 to 45 mL/min/1.73m^2 (inclusive) as determined using the Chronic Kidney Disease Epidemiology Collaboration formula, at Screening. Retesting for eGFR may be repeated twice during Screening Period.
- Confirmed clinical diagnosis of cirrhosis with either ascites or moderate hepatic impairment (Childs-Pugh B). Supporting documents confirming the participant's hepatic impairment must be available. The participant must be classified by the Investigator or usual practitioner as Child-Pugh Class B or having radiographic or clinical evidence of ascites of any grade.
- Stable hepatic impairment (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 28 days prior to Screening, as determined by the Investigator or usual practitioner).
Healthy Participants only (Cohort 2)
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and clinical laboratory tests.
- An eGFR of ≥ 90 mL/min/1.73m^2 as determined using the CKD-EPI formula at Screening.
- No clinically significant liver or kidney disease as judged by the Investigator.
Exclusion Criteria:
Medical Conditions
- Any evidence of a clinically significant disease which in the Investigator's opinion makes it undesirable for the participant to participate in the study.
- History of alcohol abuse or excessive intake of alcohol within 6 months prior to the Screening visit. Definition of excessive intake: an average weekly intake of >7 drinks/week for men or > 3.5 drinks/week for women. One drink is equivalent to (16 g of alcohol).
- Positive alcohol or drug of abuse at Screening.
- Participants with a history of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, to drugs with a similar chemical structure or class to zibotentan.
- Participants with known hypersensitivity/allergic reaction to paracetamol.
- Any signs or confirmation of coronavirus disease-19 infection.
Participants with Moderate Hepatic Impairment and Moderate Renal Impairment only (Cohort 1)
- Presence of unstable medical (eg, diabetes, epilepsy) or psychological conditions which, in the opinion of the Investigator, would compromise the participant's safety or successful participation in this study.
- Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within 28 days prior to dosing (eg, infection of ascites, fever, or active gastrointestinal bleeding).
- Severe hepatic impairment (Child-Pugh Class C Hepatic impairment), an isolated aspartate aminotransferase (AST) or alanine aminotransferase (ALT)> 5 x the upper limit of normal (ULN); or total bilirubin > 2 x ULN at time of enrolment or a concurrent increased AST and ALT of > 3 x the ULN together with a total bilirubin of > 2 x ULN. An isolated increase in bilirubin in participants with known Gilbert's syndrome is not a reason for exclusion.
- Acute liver disease caused by drug toxicity or by an infection.
- Presence of a hepatocellular carcinoma.
- Liver or renal transplantation or planned within the next 3 months at Screening.
- Receiving renal replacement therapy.
- Recent acute or subacute renal function deterioration (eg, participants with large fluctuations of creatinine values, as judged by the Investigator, and documented within 28 days prior to Screening).
- New York Heart Association functional heart failure Class III or intravenous or with unstable heart failure requiring hospitalisation for optimisation of heart failure treatment and who are not yet stable on heart failure therapy within 6 months prior to Screening.
- Abnormal resting vital signs (after resting for 10 minutes) of supine systolic blood pressure> 180 mmHg or < 100 Hg; or diastolic blood pressure> 110 mmHg or < 50 mmHg.
- Change in dose regimen of medically-required medication within the 14 days before dosing.
Healthy Participants only (Cohort 2)
- History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
Prior/Concomitant Therapy
- Use of strong or moderate inhibitors or inducers of CYP3A4 within 28 days prior to dose of zibotentan.
- Use of phosphate binders (eg, aluminium hydroxide and calcium carbonate) and acid reducing agents such as cholestyramine/colestipol, ranitidine/nizatidine, or proton pump inhibitors within 3 days before and 12 hours after dosing with zibotentan.