Pharmacokinetics of Mitiperstat in Participants With Hepatic Impairment

• Status: Not yet recruiting
• Trial end date: 2024-08-20
• Target enrollment: 0
• Participant gender: All

Summary

This study will assess the effect of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of mitiperstat.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca

Criteria

Inclusion Criteria:

• Participant must be ≥ 18 to ≤ 85 years (inclusive), at the time of signing the informed consent.

• Weight ≥ 50kg and BMI ≥ 18 kg/m2 up to < 40 kg/m2.

• Male or females of non-childbearing potential.

• Contraceptive use by males should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

1. Male participants:

Use of a condom plus an additional contraceptive method until the end of relevant systemic exposure in the exposed male plus 90 days.

2. Female participants:

Females not of child-bearing potential are defined as females who are either permanently sterilised, or who are postmenopausal.

• Capable of giving signed informed consent.

Participants with hepatic impairment only:

• Supporting documents confirming that the participant has liver cirrhosis with hepatic impairment must be available.

• Diagnosis of chronic and stable hepatic impairment.

Exclusion Criteria:

• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and HIV.

• History of substance dependence or a positive screen for drugs of abuse, likely to impact participant safety or compliance with study procedures.

• History of alcohol abuse or excessive intake of alcohol in the last 12 months.

• Abnormal vital signs, after 10 minutes supine rest at screening or Day -1.

• Any clinically important abnormalities in rhythm, conduction or morphology of the resting 12-lead ECG at screening or Day -1:

• Vulnerable participants.

• For female participants only: currently pregnant or breast-feeding.

Participants with hepatic impairment only

• Participants with previous transjugular intrahepatic portosystemic shunt (TIPS).

• Severe ascites defined as ascites requiring paracentesis and albumin at 4-week intervals or less.

• Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the screening period.

• Any evidence of additional severe or uncontrolled systemic disease or laboratory finding that makes it unsafe for the participant to participate in the study.

• Change in dose regimen of medically-required medication within the last 2 weeks before pre-study examination.

• Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.

• Clinically relevant hepatic encephalopathy.

• Oesophageal variceal bleeding in prior 3 months.

• Platelet count < 50 × 109/L and/or neutrophil count < 1.2 × 109/L and/or haemoglobin < 85 g/L.

• Post liver transplantation.

• History of acute or chronic pancreatitis, or pancreatic amylase or lipase greater than twice the ULN at screening.