How maridebart cafraglutide affects absorption of a combined oral contraceptive in postmenopausal women with overweight or obesity

A Phase 1, Open-label Study to Assess the Effect of Maridebart Cafraglutide (AMG 133) on the Pharmacokinetics of Oral Contraceptives in Postmenopausal Female Participants Living With Overweight or Obesity

This trial will test whether maridebart cafraglutide changes how a combined oral contraceptive (norgestimate and ethinyl estradiol) is absorbed and processed in postmenopausal women aged 45–65 who have overweight or obesity.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 45 Years to 65 Years
• Sex: Female
• Sponsor: Amgen (Industry-sponsored)
• Locations: 3 sites (Daytona Beach, Florida and 2 other locations)
• Trial ID: NCT07523711 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study measures the pharmacokinetics of a combined oral contraceptive when given with maridebart cafraglutide in postmenopausal women living with overweight or obesity. Eligible participants (ages 45–65, BMI 25.0–35.0 kg/m², stable weight) will receive the oral contraceptive and maridebart cafraglutide according to the protocol with serial blood sampling to quantify drug concentrations over time. Safety monitoring will include laboratory tests, vital signs, and ECGs, and participants with significant comorbidities or recent pancreatitis will be excluded. The primary endpoint is the change in PK parameters of the oral contraceptive (for example AUC and Cmax) when co-administered with maridebart cafraglutide.

Who should consider this trial

Good fit: Postmenopausal females aged 45–65 with BMI 25.0–35.0 kg/m², stable body weight, and no major medical problems or diabetes are ideal candidates.

Not a fit: People with diabetes, endocrine causes of obesity, recent or active pancreatitis, significant abnormal labs or ECGs, or BMI outside the 25–35 range would be ineligible and are unlikely to benefit from participation.

Why it matters

Potential benefit: If the drug does not alter contraceptive levels unduly, the results could help clinicians and patients use maridebart cafraglutide safely alongside combined oral contraceptives.

How similar studies have performed: Drug–drug pharmacokinetic studies have been performed for other weight-management agents and GLP-1–related compounds showing variable effects on oral drug absorption, but maridebart cafraglutide's specific interaction with combined oral contraceptives has not been established.

Eligibility criteria

Inclusion Criteria

1. Participants must be postmenopausal females 45 to 65 years of age. Postmenopausal status must be confirmed based on the protocol-defined criteria.
2. Body mass index must be 25.0 to 35.0 kg/m².
3. Body weight must be stable, with less than 5 kg self-reported change in the 3 months before screening.
4. Participants must not have changed their diet or started a nutritional lifestyle modification program within 3 months before screening.
5. Other inclusion criteria may apply.

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.
23. Other exclusion criteria may apply.

Where this trial is running

Daytona Beach, Florida and 2 other locations

• Fortrea Clinical Research Unit - Daytona Beach — Daytona Beach, Florida, United States (Recruiting)
• Fortrea Clinical Research Unit - Dallas — Dallas, Texas, United States (Recruiting)
• Fortrea Clinical Research Unit Inc. - Madison — Madison, Wisconsin, United States (Recruiting)

Study contacts

• Study coordinator: Amgen Call Center

Conditions Overweight; Obesity; Maridebart Cafraglutide; AMG 133; Norgestimate; Ethinyl Estradiol