Effect of Maridebart Cafraglutide on How Oral Contraceptives Are Absorbed and Processed in the Body in Postmenopausal Female Participants Living With Overweight or Obesity

Prior treatment

• Recent use of medications that could affect study participation, including most prescription or over-the-counter medications, systemic hormone replacement therapy, certain contraceptive hormones, CYP enzyme inducers or inhibitors, GLP-1 receptor or GIP receptor agents, and nonpermitted herbal products, vitamins, or supplements.
• Recent participation in another investigational study, prior participation in this study, or prior exposure to maridebart cafraglutide.
• Tobacco or nicotine use within 3 months before check-in, positive cotinine test, history of alcoholism or drug abuse, positive alcohol or illicit drug testing, recent illicit drug use, or unwillingness to avoid illicit drugs or cannabinoids during the study.

Other illness

• Endocrine disorders that can cause obesity, such as Cushing's syndrome.
• Bleeding or clotting disorders, abnormal coagulation tests, or a history of venous or arterial blood clots or conditions that increase clot risk.
• Malignancy within the past 5 years, except nonmelanoma skin cancer.
• Unexplained postmenopausal vaginal bleeding, untreated endometrial disease, or other gynecologic conditions that could worsen with estrogen/progestin therapy.
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, or uncontrolled thyroid disease.
• Gastroparesis, inability to swallow oral medication, clinically important gastrointestinal disease, malabsorption, uncontrolled inflammatory bowel disease, certain gastrointestinal surgeries, or recent bariatric surgery.
• Allergy, hypersensitivity, intolerance, or contraindication to maridebart cafraglutide, ethinyl estradiol, or orgestimate.
• Positive HIV test, or positive hepatitis B surface antigen or hepatitis C antibody at screening.
• Lifetime history of suicide attempt, non-suicidal self-injury within 5 years, or unstable major depressive disorder or other severe psychiatric disorder within 2 years.

Lab values

• History or evidence of any clinically significant medical condition, abnormal physical exam, ECG, vital sign, or laboratory finding that could increase risk or interfere with study participation.
• History of diabetes, active diabetes, or hemoglobin A1c 6.5% or higher.
• History of acute or chronic pancreatitis within 1 year before check-in, pancreatic enzyme elevations greater than 2 times the upper limit of normal, or fasting triglycerides greater than 300 mg/dL.
• LDL cholesterol greater than 159 mg/dL.
• Clinically significant cardiovascular disease, clinically significant arrhythmia, long QT syndrome, QTcF greater than 470 msec, second- or third-degree atrioventricular block, or clinically important abnormal pulse rate or systolic blood pressure \> 150 mmHg or \< 90 mmHg, diastolic blood pressure \> 95 mmHg or \< 50 mmHg.
• Reduced kidney function with estimated glomerular filtration rate 60 mL/min/1.73 m\^2 or lower, ALT or AST greater than 2 times the upper limit of normal, or a history of acute or chronic liver disease, hepatic adenoma, or hepatic carcinoma.
• Hemoglobin or hematocrit below the lower limit of normal.
• Recent blood, plasma, or platelet donation.

Other

• Migraine with aura, normal pressure hydrocephalus, or ischemic optic neuropathy.
• Positive pregnancy test at screening or check-in.
• Other exclusion criteria may apply.

• Participants must be postmenopausal females 45 to 65 years of age. Postmenopausal status must be confirmed based on the protocol-defined criteria.
• Body mass index must be ≥ 25.0 and ≤ 38.0 kg/m\^2.
• Body weight must be stable, with less than 5 kg self-reported change in the 3 months before screening.
• Participants must not have changed their diet or started a nutritional lifestyle modification program within 3 months before screening.
• Other inclusion criteria may apply.