Oral Contraceptive Pill (OCP) Pharmacogenomics

NCT06334315 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: 2000037337R01HD111436
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 2

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)

Conditions

Contraception; Pharmacogenomic Drug Interaction

Outcome Measures

Primary Outcomes (2)

• Serum etonogestrel concentration

  Pharmacokinetic measurement for progestin

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

• Serum ethinyl estradiol concentration

  Pharmacokinetic measurement for estrogen

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

Secondary Outcomes (6)

• 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)

• 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)

• 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)

Study Arms (1)

Combined oral contraceptive pill users

EXPERIMENTAL

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)

Drug: Desogestrel / Ethinyl Estradiol Pill

Interventions

Desogestrel / Ethinyl Estradiol Pill DRUG

Standard pill packs containing 21 active pills and 7 placebo pills

Combined oral contraceptive pill users

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• History of malabsorptive bariatric surgery
• History of cholestasis due to past oral contraceptive pill use
• Personal history of hypertension
• Personal history of ischemic heart disease
• Known thrombogenic mutations

Sponsors & Collaborators

• Yale University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Interventions

Desogestrel; Ethinyl Estradiol

Intervention Hierarchy (Ancestors)

Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Norpregnatrienes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Aaron M Lazorwitz, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aaron M Lazorwitz, MD, PhD

CONTACT

2037854688; aaron.lazorwitz@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 28, 2024
• Study Start: October 29, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: De-identified data will be uploaded to dbGaP within one year of completion of the study and will be available indefinitely
• Access Criteria: Per dbGaP requirements

Locations

US (2)