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

The primary objective of the trial is to evaluate the effect of maridebart cafraglutide on the pharmacokinetics (PK) of a combined oral contraceptive (COC) in postmenopausal female participants living with overweight or obesity.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: COC; Drug: Maridebart Cafraglutide

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117-5116
      • Recruiting
      • Fortrea Clinical Research Unit - Daytona Beach
  • Texas
    • Dallas, Texas, United States, 75247-4968
      • Recruiting
      • Fortrea Clinical Research Unit - Dallas
  • Wisconsin
    • Madison, Wisconsin, United States, 53704-2526
      • Recruiting
      • Fortrea Clinical Research Unit Inc. - Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COC + Maridebart Cafraglutide; Participants will receive COC orally and maridebart cafraglutide subcutaneously (SC).	Drug: COC; Administered orally.; Drug: Maridebart Cafraglutide; Administered as SC injection.; Other Names: AMG 133

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Concentration (Cmax) of COC	Day 1 up to Day 89
Area Under the Concentration-time Curve (AUC) from Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of COC	Day 1 up to Day 89
AUC from Time Zero Extrapolated to Infinity (AUCinf) of COC	Day 1 up to Day 89

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentrations of Maridebart Cafraglutide	Up to Day 142
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Day 1 to end of trial (approximately 142 days)
Number of Participants with Serious Adverse Events (SAEs)	From screening (Day -28) up to end of trial (approximately 170 days)
Number of Participants Who Develop Anti-maridebart Cafraglutide Antibodies	Up to Day 142

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2026
• Primary Completion (Estimated): October 7, 2026
• Study Completion (Estimated): October 7, 2026

Study Registration Dates

• First Submitted: April 6, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: AMG 133; Ethinyl Estradiol; Norgestimate; Maridebart Cafraglutide
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: 20230161

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this trial will be considered beginning 18 months after the trial 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 trial.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen trial/trials 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No