The primary objective of the trial is to evaluate the effect of AMG 133 versus placebo on acetaminophen pharmacokinetics (PK), a marker for gastric emptying, in participants living with overweight or obesity.

Inclusion Criteria:

• Male or female participants between 18 and 65 years of age.

  a. Females must not be pregnant or lactating.

• Body mass index between ≥ 27 to < 40 kg/m^2.

Exclusion Criteria:

• History or evidence of clinically significant disorder, condition, or disease not otherwise excluded that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
• History of or active diabetes or Hemoglobin A1C ≥ 6.5% (≥ 48 mmol/mol).
• History or evidence of endocrine disorder.
• History of acute or chronic pancreatitis within 1 year, or elevation in serum lipase/amylase (> 2 x the upper limit of normal [ULN]), or fasting serum triglyceride level of > 500 mg/dL.
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
• Uncontrolled thyroid disease.
• History of or current signs of gastroparesis.
• History or current signs or symptoms of cardiovascular disease.
• History suggestive of esophageal, gastric, or duodenal ulceration or bowel disease; or a history of gastrointestinal surgery other than uncomplicated appendectomy or hernia repair.
• History of gastrointestinal tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, gastric/jejunal tube feeds, or uncontrolled inflammatory gastrointestinal disease.
• History of hypersensitivity, intolerance, or allergy to AMG 133 or related/similar compounds or acetaminophen or their ingredients.
• Any contraindication to acetaminophen according to the applicable labelling.
• Inability to swallow oral medication.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x the upper limit of normal.
• Use of any over-the-counter or prescription medications within 30 days or 5 half-lives.
• Current use or prior use of any glucagon-like peptide 1 receptor (GLP-1R) agonist, or glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist or antagonist within the past 3 months.
• Current or prior use of all herbal medicines (e.g., St. John's wort), vitamins, and supplements consumed by the participant within the 30 days prior to enrollment.
• Participant has received a dose of an investigational medicinal product (IMP) within the past 30 days or 5 half-lives.
• Have previously completed or withdrawn from this study or any other study investigating AMG 133 or have previously received the IMP.
• Current use of acute or chronic medication known to affect gastric emptying.

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.