Evaluating how genetics affect the effectiveness of oral contraceptive pills

Influence of Genetics Variants on the Pharmacokinetics and Pharmacodynamics of Combined Oral Contraceptive Pill Users

This study is testing if a specific genetic variation affects how well oral contraceptive pills work for women aged 18-45.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 700 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: Yale University (Academic / other)
• Locations: 2 sites (Aurora, Colorado and 1 other locations)
• Trial ID: NCT06334315 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to investigate how genetic variations, specifically the CYP3A7*1C variant, influence the metabolism of hormones in oral contraceptive pills, potentially affecting their efficacy and side effects. The study will assess whether individuals with this genetic variant metabolize desogestrel and ethinyl estradiol differently and if they experience higher rates of breakthrough ovulation. By understanding these genetic factors, the trial seeks to identify novel genetic loci associated with variations in hormone pharmacokinetics and pharmacodynamics. Participants will be women aged 18-45 who are in good health and willing to adhere to the study protocols.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy women aged 18-45 who are willing to take oral contraceptives and comply with study protocols.

Not a fit: Patients currently taking medications that induce or inhibit CYP3A may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized contraceptive options that are more effective and have fewer side effects for women based on their genetic makeup.

How similar studies have performed: Other studies have explored pharmacogenomics in contraceptive efficacy, but this specific approach focusing on the CYP3A7*1C variant is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Female, aged 18-45 years old
4. In good general health as evidenced by medical history and no need for regular intensive medical interventions (e.g., inpatient admissions, surgical treatments). The Principal Investigator will be responsible for determining good general health for potential participants with complicated medical histories.
5. Ability to take oral medication and be willing to adhere to the oral contraceptive pill (DSG/EE) regimen
6. Body-mass index ≥18.5kg/m2
7. Willing to abstain from medications and supplements known to induce/inhibit CYP3A (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort) during the study
8. Normal blood pressure measurement at study screening
9. Negative urine pregnancy test at study screening

Exclusion Criteria:

1. Currently taking any known CYP3A inducers/inhibitors (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort)43
2. Any medical conditions that affect liver function (e.g., hepatitis, cirrhosis)
3. Contraindications to estrogen-containing contraception (based on category 3 or 4 recommendations in the CDC MEC guidelines42)

   1. Current breast cancer or personal history of breast cancer
   2. Severe decompensated cirrhosis
   3. Personal history of deep venous thrombosis or pulmonary embolism
   4. Recent major surgery with prolonged immobilization
   5. Diabetes with nephropathy, retinopathy, neuropathy, or other vascular disease
   6. Current gallbladder disease
   7. Migraine headaches with aura
   8. History of malabsorptive bariatric surgery
   9. History of cholestasis due to past oral contraceptive pill use
   10. Personal history of hypertension
   11. Personal history of ischemic heart disease
   12. Known thrombogenic mutations
   13. Personal history of focal nodular hyperplasia of the liver, hepatocellular adenoma, or malignant hepatoma
   14. Multiple sclerosis with prolonged immobility
   15. History of peripartum cardiomyopathy
   16. Current tobacco smoker and age ≥35 years
   17. History of complicated solid organ transplantation
   18. Personal history of stroke
   19. Personal history of superficial venous thrombosis
   20. Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies
   21. Complicated valvular heart disease
   22. Current use of fosamprenavir or lamotrigine
4. Use of injectable contraceptive method within 6 months or current use of an ENG implant
5. Childbirth within 6 months

Where this trial is running

Aurora, Colorado and 1 other locations

• University of Colorado Anschutz Medical Campus — Aurora, Colorado, United States (Not_yet_recruiting)
• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Aaron M Lazorwitz, MD, PhD — Yale University
• Study coordinator: Aaron M Lazorwitz, MD, PhD

Conditions Contraception; Pharmacogenomic Drug Interaction