A Study to Evaluate AMG 133 in Participants With Varying Degrees of Hepatic Impairment or Normal Hepatic Function

Inclusion criteria

• Adults 18 to 75 years of age, male or female.
• Body mass index ≥ 22 kg/m^2 at screening.
• For participants with normal hepatic function:

• In good health with no clinically significant findings from medical history, physical exam, electrocardiogram (ECG), vital signs, or laboratory tests.
• Systolic blood pressure (BP) 90-150 mmHg and diastolic BP 50-100 mmHg; pulse 40-110 bpm.
• Stable body weight (< 5 kg change) and no recent dietary modifications within 3 months.
• For participants with hepatic impairment:

• Documented Child-Pugh Class A (mild), B (moderate), or C (severe) hepatic impairment.
• Clinically stable chronic liver disease (e.g., cirrhosis, hepatitis B, alcoholic liver disease, or stable hepatitis C).
• Systolic BP ≤ 170 mmHg and diastolic BP ≤ 100 mmHg.
• Willing to use reliable contraception (if of childbearing potential) or practice abstinence through 16 weeks after dosing.

Exclusion criteria

• Any unstable medical condition (e.g., recent hospitalization or major surgery).
• History of acute or chronic pancreatitis within 1 year or lipase/amylase > 2× ULN at screening.
• Endocrine disorder that can cause obesity (e.g., Cushing's syndrome).
• Significant cardiac conditions (e.g., clinically meaningful arrhythmias, 2nd/3rd-degree AV block, QT Interval Corrected Using Fridericia's Formula (QTcF) >450 msec men / >470 msec women for normal hepatic group; > 490 msec men / > 500 msec women for hepatic impairment).
• Estimated glomerular filtration rate < 60 mL/min/1.73 m^2 (normal/mild) or < 50 mL/min/1.73 m^2 (moderate/severe impairment).
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
• Uncontrolled thyroid disease or clinically significant gastroparesis.
• Prior bariatric surgery within 6 months.
• Poor venous access.
• Positive Human Immunodeficiency Virus (HIV) test.
• Hypersensitivity to AMG 133 or its components.
• Current use of GLP-1 or GIP receptor agents within 3 months.
• Pregnancy or lactation, or unwillingness to follow contraception requirements.
• History of substance or alcohol abuse within 1 year or current alcohol intake > 21 units/week (men) or > 14 units/week (women).
• Positive test for hepatitis B surface antigen or active hepatitis C (with unstable disease).
• Diabetes mellitus not meeting glycemic cutoffs (hemoglobin A1C ≥ 6.5 % for normal hepatic group or > 11 % for hepatic impairment group).
• Active malignancy (within 18 months for hepatic impairment group; within 5 years for normal hepatic group).
• Hepatic encephalopathy Grade ≥ 3 (uncontrolled) or severe uncontrolled ascites.
• Organ transplant recipients or those on immunosuppressants.
• Participation in another clinical trial within 30 days or 5 drug half-lives (whichever is longer).