Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity

Inclusion Criteria

• Participant has provided informed consent before initiation of any study-specific activities/procedures.
• Age ≥ 18 years to ≤ 65 years, at the time of signing the informed consent.
• Except for obesity, otherwise healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and ECGs on day -2 (cohorts 1-6, cohort 11-13) or day -1 (cohorts 7-10) and screening.
• Body mass index between ≥ 30.0 kg/m^2 and ≤ 40.0 kg/m^2.
• Have a stable body weight ( 40 IU/L or according to the definition of "postmenopausal range" for the laboratory involved; OR
• History of hysterectomy; OR
• History of bilateral oophorectomy.
• For patients in cohorts 7-10 only, participants must have a smartphone device with the capability of downloading apps or other digital tools required for this cohort.

Exclusion Criteria

• History or clinical evidence of diabetes mellitus, including hemoglobin A1c (HbA1c) > 6.5% and/or a fasting glucose ≥ 125 mg/dl (6.9 mmol/L) at screening.
• Triglycerides ≥ 5.65 mmol/L (ie, 500 mg/dL) at screening.
• Screening calcitonin ≥ 50 ng/L.
• Hepatic liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin levels > 1.5 times the upper limit of normal (ULN) at screening. If ALT is > 1.5 x the ULN at screening AND the AST, alkaline phosphatase, and total bilirubin levels are within normal limits, then participant may be eligible for enrollment after a discussion with the medical monitor.
• History or clinical evidence of bleeding diathesis or any coagulation disorder, including prothrombin time (PT), activated partial thromboplastin time (PTT), international normalized ratio (INR), or platelet count outside of the laboratory's normal reference range at screening. If a single value (PT, PTT, INR, or platelet count) is outside the normal reference range at screening and the participant does not have evidence of any other bleeding or coagulation disorder, then the participant may be eligible for enrollment after a discussion with the medical monitor.
• History of gastrointestinal abnormality that could affect gastrointestinal motility (including small bowel or colonic resection, inflammatory bowel disease, irritable bowel disease, and colon or gastrointestinal tract cancer).
• Participants with a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 or a personal history of nonfamilial medullary thyroid carcinoma.
• Participants with a history of confirmed chronic pancreatitis or idiopathic acute pancreatitis.
• Participants with a history of gall bladder disease (ie, cholelithiasis or cholecystitis) not treated with cholecystectomy.
• Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid stimulating hormone > 6 mIU/L or 450 msec in males or > 470 msec in females or history of long QT syndrome.
• Participants with a history of renal impairment or renal disease and/or estimated glomerular filtration rate ≤ 60 mL/min/1.73 m^2.
• Obesity induced by other endocrinologic disorders (eg, Cushing's Syndrome).
• Previous surgical treatment for obesity (excluding liposuction if performed >1 year before study entry) and/or participants with recent (within 6 months) or planned endoscopic treatment for obesity.
• History of major depressive disorder.
• History of other severe psychiatric disorders, eg schizophrenia, bipolar disorder.
• Any lifetime history of a suicidal attempt or of any suicidal behavior.
• Surgery scheduled for the study duration period, except for minor surgical procedures, at the discretion of the investigator.
• Positive results for human immunodeficiency virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus RNA. For hepatitis C, hepatitis C antibody testing is done at screening, followed by hepatitis C virus RNA by polymera