A Trial to Assess Bioavailability of AMG 133 in Participants With Overweight or Obesity

1. Provide signed and dated informed consent before any study procedures.
2. Be male or female, 18 to 65 years old, at screening.
3. May have well-controlled conditions such as obstructive sleep apnea, high blood pressure, high cholesterol, or hypothyroidism on stable treatment for ≥ 3 months. Other mild, stable health conditions may be allowed with investigator and medical monitor approval.
4. Body mass index (BMI) between 25 and 40 kg/m² at screening.
5. Stable body weight (less than 5 kg change by self-report) during the 3 months before screening.
6. No major changes in diet or lifestyle (such as new weight-loss or exercise programs) during the past 3 months.

Exclusion Criteria:

1. Any significant medical condition or abnormal test result that could increase risk or interfere with study participation, based on investigator judgment.
2. Diabetes (any type except past gestational diabetes) or Hemoglobin A1c (HbA1c) ≥ 6.5%.
3. Endocrine disorders that can cause obesity (for example, Cushing's syndrome).
4. Pancreatitis within the past year, or abnormal pancreatic blood tests (lipase/amylase > 2 × normal) or fasting triglycerides > 500 mg/dL.
5. Cancer within 5 years (except treated non-melanoma skin cancer or in-situ cervical/breast lesions).
6. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
7. Uncontrolled thyroid disease (thyroid stimulating hormone [TSH] > 6.0 or \< 0.4 mIU/L). Participants on stable thyroid-replacement therapy for ≥ 3 months may be included if TSH is in range.
8. History or current signs of gastroparesis (delayed stomach emptying).
9. Weight-loss surgery within 6 months before check-in.
10. Heart or blood-vessel disease (aside from controlled high blood pressure or cholesterol), such as heart attack, angina, valve disease, or prior bypass/stent.
11. Clinically significant abnormal heart rhythm on electrocardiogram (ECG) at screening or check-in.
12. QT corrected for heart rate using Fridericia's method (QTcF) > 450 ms (males) or > 470 ms (females), or a history of long QT syndrome.
13. Second- or third-degree heart block.
14. Blood pressure > 150/95 mmHg or \< 90/50 mmHg, or pulse > 110 bpm. A single repeat is allowed if values normalize.
15. Allergy or hypersensitivity to AMG 133 or its ingredients.
16. Poor veins for blood draws.
17. Kidney function (estimated glomerular filtration rate [eGFR]) ≤ 60 mL/min/1.73 m\^2.
18. Liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) > 2X normal.
19. Positive test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) (exceptions apply for prior vaccination or resolved hepatitis B virus [HBV] infection).
20. Current or recent (within 6 months) suicidal thoughts, suicide attempts, or major psychiatric illness, including depression.

21. Use of any prescription or over-the-counter medicines within 30 days or 5 half-lives (whichever is longer) before check-in, except:

    • Acetaminophen ≤ 2 g/day for pain
    • Hormone replacement (e.g., estrogen, thyroid) or hormonal contraception
    • Stable treatments (≥ 3 months) for high blood pressure, high cholesterol, or other mild, well-controlled conditions approved by the investigator and medical monitor.
22. Use of any glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic polypeptide (GIP) receptor agonist/antagonist within 3 months.
23. Use of herbal medicines, vitamins, or supplements within 30 days, unless approved by the investigator and sponsor.
24. Consumption of poppy-seed-containing foods within 7 days before check-in.
25. Alcohol abuse or regular intake > 21 units/week (men) or > 14 units/week (women), or drug abuse within 1 year. (1 unit = 12 oz beer, 1.5 oz liquor, 5 oz wine.)
26. Alcohol use within 48 hours before check-in, or unwillingness to limit alcohol to ≤ 1 unit/day from discharge through study end.
27. Strenuous exercise or a new exercise program within 7 days before check-in.
28. Positive drug screen or tetrahydrocannabinol (THC) test, or unwillingness to avoid illicit drugs/THC through end of study.
29. Positive pregnancy test at screening or check-in.
30. Breastfeeding, or planning to breastfeed within 16 weeks after receiving AMG 133.
31. Men and women unwilling to use required contraception through 16 weeks after receiving AMG 133.
32. Men unwilling to abstain from sperm donation or women unwilling to abstain from egg donation through 16 weeks after receiving AMG 133.
33. Men with female partners of childbearing potential unwilling to inform their partner and adhere to contraception requirements.
34. Men with pregnant partners (or partners planning pregnancy) unwilling to use effective contraception or abstain from intercourse through 16 weeks after receiving AMG 133.
35. Participation in another investigational drug study within 30 days or 5 half-lives (whichever is longer).
36. Previous participation in any study of AMG 133.
37. Blood donation within 3 months, plasma within 2 weeks, or platelets within 6 weeks before check-in.
38. Unwillingness to follow study requirements or restrictions.
39. Any other reason, in the investigator's opinion, that makes participation unsuitable.