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

Exclusion Criteria

• •1. 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.
• •2. History of diabetes, active diabetes, or hemoglobin A1c 6.5% or higher.
• •3. Endocrine disorders that can cause obesity, such as Cushing's syndrome.
• •4. 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.
• •5. Bleeding or clotting disorders, abnormal coagulation tests, or a history of venous or arterial blood clots or conditions that increase clot risk.
• •6. LDL cholesterol greater than 159 mg/dL.
• •7. Migraine with aura, normal pressure hydrocephalus, or ischemic optic neuropathy.
• •8. Malignancy within the past 5 years, except nonmelanoma skin cancer.
• •9. Unexplained postmenopausal vaginal bleeding, untreated endometrial disease, or other gynecologic conditions that could worsen with estrogen/progestin therapy.
• •10. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, or uncontrolled thyroid disease.
• •11. Gastroparesis, inability to swallow oral medication, clinically important gastrointestinal disease, malabsorption, uncontrolled inflammatory bowel disease, certain gastrointestinal surgeries, or recent bariatric surgery.
• •12. 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 blood pressure or pulse rate.
• •13. Allergy, hypersensitivity, intolerance, or contraindication to maridebart cafraglutide, ethinyl estradiol, or orgestimate.
• •14. Reduced kidney function with estimated glomerular filtration rate 60 mL/min/1.73 m² 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.
• •15. Hemoglobin or hematocrit below the lower limit of normal.
• •16. Positive HIV test, or positive hepatitis B surface antigen or hepatitis C antibody at screening.
• •17. 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.
• •18. Positive pregnancy test at screening or check-in.
• •19. 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.
• •20. Recent participation in another investigational study, prior participation in this study, or prior exposure to maridebart cafraglutide.
• •21. 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.
• •22. Recent blood, plasma, or platelet donation.