Hepatic Impairment
Conditions
Keywords
Liver disease
Brief summary
The primary objective of the trial is to evaluate the pharmacokinetics (PK) of AMG 133 after a single subcutaneous (SC) dose in participants with mild, moderate, or severe hepatic impairment compared to participants with normal hepatic function.
Interventions
DRUGAMG 133
Participants will receive AMG 133 SC.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Adults 18 to 75 years of age, male or female. 2. Body mass index ≥ 22 kg/m\^2 at screening. 3. 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. 4. 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. 5. Willing to use reliable contraception (if of childbearing potential) or practice abstinence through 16 weeks after dosing.
Exclusion criteria
1. Any unstable medical condition (e.g., recent hospitalization or major surgery). 2. History of acute or chronic pancreatitis within 1 year or lipase/amylase \> 2× ULN at screening. 3. Endocrine disorder that can cause obesity (e.g., Cushing's syndrome). 4. 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). 5. Estimated glomerular filtration rate \< 60 mL/min/1.73 m\^2 (normal/mild) or \< 50 mL/min/1.73 m\^2 (moderate/severe impairment). 6. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. 7. Uncontrolled thyroid disease or clinically significant gastroparesis. 8. Prior bariatric surgery within 6 months. 9. Poor venous access. 10. Positive Human Immunodeficiency Virus (HIV) test. 11. Hypersensitivity to AMG 133 or its components. 12. Current use of GLP-1 or GIP receptor agents within 3 months. 13. Pregnancy or lactation, or unwillingness to follow contraception requirements. 14. History of substance or alcohol abuse within 1 year or current alcohol intake \> 21 units/week (men) or \> 14 units/week (women). 15. Positive test for hepatitis B surface antigen or active hepatitis C (with unstable disease). 16. Diabetes mellitus not meeting glycemic cutoffs (hemoglobin A1C ≥ 6.5 % for normal hepatic group or \> 11 % for hepatic impairment group). 17. Active malignancy (within 18 months for hepatic impairment group; within 5 years for normal hepatic group). 18. Hepatic encephalopathy Grade ≥ 3 (uncontrolled) or severe uncontrolled ascites. 19. Organ transplant recipients or those on immunosuppressants. 20. Participation in another clinical trial within 30 days or 5 drug half-lives (whichever is longer).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of AMG 133 | Up to Day 120 |
| Area Under the Plasma Concentration-time Curve (AUC) from Time Zero to Time of Last Quantifiable Concentration (AUClast) of AMG 133 | Up to Day 120 |
| AUC from Time Zero to Infinity (AUCinf) of AMG 133 | Up to Day 120 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Up to Day 120 |
| Number of Participants Who Experience Serious Adverse Events (SAEs) | Up to Day 120 |
| Number of Participants Who Develop Anti-AMG 133 Antibodies | Up to Day 120 |
Countries
United States
Contacts
STUDY_DIRECTORMD
Amgen
Outcome results
None listed