Pharmacokinetics of Cotadutide in Participants with Hepatic Impairment

Exclusion Criteria

• All participants
• - History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to cotadutide.
• - Any clinically important abnormalities in rhythm, conduction or morphology of the 12-lead resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QT interval corrected for heart rate using Fridericia’s formula (QTcF), including abnormal ST-T-wave morphology, or left ventricular hypertrophy
• (a) Prolonged QTcF > 470 ms or family history of long QT syndrome.
• (b) PR (PQ) interval shortening < 120 ms.
• (c) PR (PQ) interval prolongation (> 220 ms) intermittent or permanent second or third degree atrioventricular (AV) block, or AV dissociation.
• (d) Persistent or intermittent complete bundle branch block, or intraventricular conduction delay with QRS > 119 ms.
• - Any evidence of additional severe or uncontrolled systemic disease or laboratory finding that makes it unsafe for the participant to participate in the study.
• - Impaired renal function, defined as estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 at Screening.
• - Any positive result on Screening for serum hepatitis B surface antigen, anti-Core HBV antibody, hepatitis C antibody, or human immunodeficiency virus (HIV).
• - Any sign and confirmation of coronavirus disease 2019 (COVID19) infection:
• - Participants with concurrent or previous use of a glucagon-like peptide-1 (GLP1) receptor agonist.
• - Use of prohibited prescribed or nonprescribed medication during the 2 weeks prior to the first administration of Investigational Medicinal Product (IMP) or longer if the medication has a long half-life.
• - History of neoplastic disease within 5 years prior to Screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer.
• - Presence of hepatocellular carcinoma or acute liver disease caused by an infection or drug toxicity.
• Participants with hepatic impairment only
• - Severe portal hypertension or surgical porto-systemic shunts.
• - Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
• - Clinically relevant hepatic encephalopathy.
• - 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 28-day Screening period.
• - Post liver transplantation.
• - Platelet count < 50 × 109/L and/or neutrophil count < 1.2 × 109/L and/or hemoglobin < 8.5 g/dL or INR >2.3.
• Participants with normal hepatic function only
• - History or presence of hepatic disease or evidence of other known forms of known chronic liver disease.
• - History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• - Urinary albumin-to-creatinine ratio > 3 mg/μmol.