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

Yale University2 sites in 1 country700 target enrollmentOctober 29, 2024

ConditionsContraception Pharmacogenomic Drug Interaction

InterventionsDesogestrel / Ethinyl Estradiol Pill

DrugsDesogestrel / Ethinyl Estradiol Pill

Overview

Phase: Phase 4
Intervention: Desogestrel / Ethinyl Estradiol Pill
Conditions: Contraception
Sponsor: Yale University
Enrollment: 700
Locations: 2
Primary Endpoint: Serum etonogestrel concentration
Status: Recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The goal of this clinical trial is to evaluate how differences in specific parts of our DNA can influence how individual bodies break down the hormones contained within oral contraceptive pills, which could affect how well these birth control pills work to prevent pregnancy. The investigators are also interested in exploring how these differences in our DNA can also explain why patients taking the exact same formulation of birth control pill will experience very different side effects. The main questions it aims to answer are:

Do individuals with the CYP3A7*1C variant have increased metabolism of both desogestrel and ethinyl estradiol when taking a combined oral contraceptive pill?
Do individuals with the CYP3A7*1C variant experience higher rates of breakthrough ovulation while taking a desogestrel/ethinyl estradiol combined oral contraceptive pill?
What novel genetic loci are associated with alterations in steroid hormone pharmacokinetics and pharmacodynamics among a larger cohort of combined oral contraceptive pill users?

Participants will take a specific formulation of combined oral contraceptive pill (desogestrel/ethinyl estradiol) and undergo the following procedures:

Blood draw to measure the amount of progestin and estrogen in their system from the combined oral contraceptive pill
Questionnaires to assess side effects possibly caused by the combined oral contraceptive pill
Blood draw to measure endogenous hormone levels and biomarkers that may be affected by the combined oral contraceptive pill
A transvaginal ultrasound to measure any ovarian follicles (optional procedure)

Registry

clinicaltrials.gov

Start Date

October 29, 2024

End Date

May 1, 2028

Last Updated

8 months ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Yale University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provision of signed and dated informed consent form
•Stated willingness to comply with all study procedures and availability for the duration of the study
•Female, aged 18-45 years old
•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.
•Ability to take oral medication and be willing to adhere to the oral contraceptive pill (DSG/EE) regimen
•Body-mass index ≥18.5kg/m2
•Willing to abstain from medications and supplements known to induce/inhibit CYP3A (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort) during the study
•Normal blood pressure measurement at study screening
•Negative urine pregnancy test at study screening

Exclusion Criteria

•Currently taking any known CYP3A inducers/inhibitors (e.g., rifampin, carbamazepine, ketoconazole, St. John's wort)43
•Any medical conditions that affect liver function (e.g., hepatitis, cirrhosis)
•Contraindications to estrogen-containing contraception (based on category 3 or 4 recommendations in the CDC MEC guidelines42)
•Current breast cancer or personal history of breast cancer
•Severe decompensated cirrhosis
•Personal history of deep venous thrombosis or pulmonary embolism
•Recent major surgery with prolonged immobilization
•Diabetes with nephropathy, retinopathy, neuropathy, or other vascular disease
•Current gallbladder disease
•Migraine headaches with aura

Arms & Interventions

Combined oral contraceptive pill users

Administered a combined oral contraceptive pill containing desogestrel and ethinyl estradiol (Desogen, 0.15mg desogestrel and 0.03mg ethinyl estradiol per active pill) for at least one cycle (21 days) and up to 13 total cycles (one year)

Intervention: Desogestrel / Ethinyl Estradiol Pill

Outcomes

Primary Outcomes

Serum etonogestrel concentration

Time Frame: Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days)

Pharmacokinetic measurement for progestin

Serum ethinyl estradiol concentration

Time Frame: Measured as a trough concentration on Cycle 1, Day 22 (each cycle is 28 days)

Pharmacokinetic measurement for estrogen

Secondary Outcomes

Serum progesterone concentration(Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days))
Serum estradiol concentration(Measured on Cycle 1, Day 22 (all participants), repeated measure in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days))
Modified Hoogland score(Measured on Cycle 1, Day 22 (optional study procedure) (each cycle is 28 days))
Positive and Negative Affect Scheduled(Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeated measurements again in Cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days))
Sex hormone binding globulin levels(Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeat measurements in cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days))
Serum albumin concentration(Baseline measured at enrollment, repeat measurement at Cycle 1, Day 22 (all participants), repeat measurements in cycles 3, 6, and 13 (optional study procedures) (each cycle is 28 days))