Birth Control Pills and DNA Interaction

Recruiting at 2 trial locations

Overseen By Aaron Lazorwitz, MD, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Yale University

Must be taking: Oral contraceptives

Must not be taking: CYP3A inducers/inhibitors

Disqualifiers: Liver disease, Breast cancer, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 months

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how DNA affects the body's processing of birth control pills, specifically those containing desogestrel and ethinyl estradiol. Researchers aim to determine if certain DNA differences influence the pill's effectiveness in preventing pregnancy and the variation in side effects among individuals. Participants will take the pill for up to a year, with blood tests and optional ultrasounds to monitor hormone levels and side effects. Women who have used birth control pills but not injectable contraceptives or implants recently, and who do not smoke or have certain health issues, might be suitable candidates. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial requires participants to stop taking medications and supplements known to affect CYP3A, such as rifampin, carbamazepine, ketoconazole, and St. John's wort, during the study.

What is the safety track record for this treatment?

Research shows that the birth control pills in this trial, containing desogestrel and ethinyl estradiol, are generally safe for most people. These pills are widely used to prevent pregnancy and have FDA approval.

However, studies have found some risks, such as an increased chance of blood clots. This risk is well-known and associated with many types of birth control pills. Despite this, many people use these pills without serious problems. Discuss any concerns with a healthcare provider, especially if there is a family history of blood clots.

Overall, while some side effects are known, many people tolerate this treatment well. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike other birth control options, which often focus solely on preventing pregnancy, the combination of desogestrel and ethinyl estradiol in this pill is being explored for its unique interaction with DNA. Researchers are excited about this treatment because it could provide insights into how hormonal contraceptives might influence genetic material, potentially leading to more personalized and effective birth control solutions. This exploration into the DNA interaction is what sets this treatment apart from other standard contraceptives, which primarily include options like the combination pill with different active ingredients or progestin-only pills.

What evidence suggests that this treatment might be an effective birth control method?

Research has shown that the combined birth control pill containing desogestrel and ethinyl estradiol, which participants in this trial will use, is about 99% effective at preventing pregnancy when used correctly. The pill prevents the egg from fully developing, stopping fertilization. Studies have found that individuals who take these pills as directed have a low chance of unintended pregnancies. Additionally, this type of birth control is well-researched and widely used, with only minor side effects like irregular bleeding for some users. Overall, this combination pill is considered highly effective for preventing pregnancy. ^{1 2 6 7 8}

Who Is on the Research Team?

Aaron M Lazorwitz, MD, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals using a specific birth control pill (desogestrel/ethinyl estradiol). It's focused on how genetic differences affect the body's processing of these hormones and their effectiveness in preventing pregnancy. Participants will have blood tests, answer questionnaires about side effects, and may opt for an ultrasound to check ovarian follicles.

Inclusion Criteria

Body-mass index ≥18.5kg/m2

Normal blood pressure measurement at study screening

Negative urine pregnancy test at study screening

Exclusion Criteria

Use of injectable contraceptive method within 6 months or current use of an ENG implant

Childbirth within 6 months

History of complicated solid organ transplantation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are administered a combined oral contraceptive pill containing desogestrel and ethinyl estradiol for at least one cycle (21 days) and up to 13 total cycles (one year)

12 months

Monthly visits for blood draws and questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment, including optional transvaginal ultrasound and repeated blood draws

4 weeks

1-2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Desogestrel / Ethinyl Estradiol Pill

Trial Overview

The study is testing how the CYP3A7*1C gene variant affects metabolism of hormones in oral contraceptives and if it leads to more cases of breakthrough ovulation. It also seeks new genetic factors that influence hormone levels among users of these pills.

How Is the Trial Designed?

Group I: Combined oral contraceptive pill users Experimental Treatment 1 Intervention

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)

Desogestrel / Ethinyl Estradiol Pill is already approved in United States, European Union for the following indications:

Approved in United States as Desogen for:

• Prevention of pregnancy

Approved in European Union as Desogen for:

• Prevention of pregnancy

Approved in United States as Kariva for:

• Prevention of pregnancy

Approved in United States as Reclipsen for:

• Prevention of pregnancy

Approved in United States as Azurette for:

• Prevention of pregnancy

Approved in United States as Cyclessa for:

• Prevention of pregnancy

Approved in United States as Isibloom for:

• Prevention of pregnancy

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

The study involving 1,221 women over 11,656 cycles showed that the oral contraceptive containing 150 micrograms of desogestrel and 30 micrograms of ethinyl estradiol was highly effective, with no pregnancies due to method failure.

The contraceptive was well tolerated, with less than 2% of participants discontinuing due to bleeding irregularities, and it showed no adverse effects on cervical health, blood pressure, or body weight, indicating its safety and acceptability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter efficacy and safety study of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol. Walling, M.[2019]

In a study of 350 contraceptive implant users, self-reported race and ethnicity were found to be strong indicators of genetically determined ancestry, suggesting that these social factors are important in understanding progestin-related side effects.

The analysis revealed no significant associations between genetically determined ancestry or self-reported race/ethnicity and serum etonogestrel concentrations, indicating that these factors do not affect the pharmacokinetics of the contraceptive implant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applicability of ancestral genotyping in pharmacogenomic research with hormonal contraception. Lazorwitz, A., Aquilante, CL., Shortt, JA., et al.[2022]

Desogestrel, combined with ethinyl estradiol in the oral contraceptive Marvelon, demonstrated a low use-effectiveness rate of 0.58 Pearl Units across 4074 cycles involving 219 women, indicating its reliability as a contraceptive method.

The study reported no serious side effects associated with the contraceptive, and the drug-related discontinuation rate was relatively low at 12.8% over six months, suggesting good tolerability among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with an ethinyl estradiol-desogestrel oral contraceptive. Van Trappen, Y., Duvivier, P., Thiery, M., et al.[2013]

Oral contraceptive steroids can have significant drug interactions, where certain medications, especially enzyme-inducing anticonvulsants like phenobarbital and rifampicin, can reduce the effectiveness of contraceptives, potentially leading to breakthrough bleeding or unintended pregnancy.

Conversely, some substances like ascorbic acid and paracetamol can increase blood levels of ethinylestradiol, the active component in many oral contraceptives, which may affect contraceptive efficacy, particularly in women taking high doses of these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic drug interactions with oral contraceptives. Back, DJ., Orme, ML.[2018]

The desogestrel-only pill Cerazette effectively inhibits ovulation even when taken up to 12 hours late, with only 1% of the 103 women in the study experiencing ovulation during treatment.

Return to ovulation after stopping Cerazette takes at least 7 days, highlighting its reliability as a contraceptive method compared to traditional progestagen-only pills.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance of ovulation inhibition with the 75-microg desogestrel-only contraceptive pill (Cerazette) after scheduled 12-h delays in tablet intake. Korver, T., Klipping, C., Heger-Mahn, D., et al.[2013]

The clinical trial with 1,159 women demonstrated that an oral contraceptive containing 150 micrograms of desogestrel and 30 micrograms of ethinyl estradiol is highly effective for preventing pregnancy over 15,222 observed cycles.

The contraceptive showed good cycle control with no serious side effects reported, and minor complaints were less frequent compared to cycles without treatment, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial of an oral contraceptive containing desogestrel and ethinyl estradiol. Weijers, MJ.[2013]

Desogestrel 75 micrograms/day demonstrated superior contraceptive efficacy compared to levonorgestrel 30 micrograms/day, with a Pearl index of 0.14 versus 1.17, indicating fewer pregnancies among users.

Both contraceptive methods had similar safety profiles and overall acceptability, but desogestrel users experienced a more varied bleeding pattern, including higher rates of amenorrhea and infrequent bleeding, especially at the start of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind study comparing the contraceptive efficacy, acceptability and safety of two progestogen-only pills containing desogestrel 75 micrograms/day or levonorgestrel 30 micrograms/day. Collaborative Study Group on the Desogestrel-containing Progestogen-only Pill. [2019]

New generation oral contraceptives like desogestrel and gestodene are similarly effective in preventing pregnancy and managing menstrual cycles, while also offering a better metabolic profile compared to older contraceptives.

Desogestrel-containing contraceptives have shown effectiveness in treating mild to moderate acne and hirsutism, and their varying estrogen doses allow for personalized treatment options based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classification and comparison of oral contraceptives containing new generation progestogens. Newton, JR.[2019]

Mothers taking combined oral contraceptives can safely breast-feed, as the concentrations of hormones like levonorgestrel and ethinylestradiol in breast milk are low.

Newer progestogens such as desogestrel, gestodene, and norgestimate show good bioavailability, but their effectiveness can be influenced by factors like sex hormone binding globulin (SHBG) levels and interactions with other medications, which may affect contraceptive efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of contraceptive steroids. An update. Shenfield, GM., Griffin, JM.[2018]

A study involving 43 healthy women taking different types of low-dose oral contraceptive pills for 12 menstrual cycles found no significant increase in chromosomal aberrations or sister chromatid exchange compared to a control group.

The three types of oral contraceptives tested (desogestrel, norgestrel, and gestodene) did not show any statistically significant differences in their genotoxic effects, suggesting they are safe in terms of chromosomal integrity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of genetic damage in human lymphocytes of women using oral contraceptives. Mahrous, HS.[2020]

Drospirenone and ethinylestradiol, components of common oral contraceptives, were found to cause DNA damage in human breast cells and female mouse bone marrow cells, indicating potential genotoxic effects.

The study revealed that the combination of these two drugs increased DNA damage, suggesting that long-term use of these contraceptives may elevate the risk of cancer development in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotoxic effects of drospirenone and ethinylestradiol in human breast cells (in vitro) and bone marrow cells of female mice (in vivo). Mir, AH., Dumka, VK., Sultan, F., et al.[2022]

Citations

1.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK430882/

Oral Contraceptive Pills - StatPearls - NCBI Bookshelf - NIH

Currently, 3 types of oral contraceptive pills are broadly prescribed: combined estrogen-progesterone, progesterone-only, and continuous or extended-use pills.

2.

mayoclinic.org

mayoclinic.org/drugs-supplements/desogestrel-and-ethinyl-estradiol-oral-route/description/drg-20061362

Desogestrel and ethinyl estradiol (oral route) - Side effects ...

It works by stopping a woman's egg from fully developing each month. The egg can no longer accept a sperm and fertilization (pregnancy) is prevented. No ...

3.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2022/021090s009lbl.pdf

CYCLESSA® Tablets (desogestrel and ethinyl estradiol ...

Oral contraceptives are highly effective. Table 2 lists the typical unintended pregnancy rates for users of combination oral contraceptives and other methods of ...

4.

goodrx.com

goodrx.com/kariva/what-is?srsltid=AfmBOoqFuo0RTn7HbDNC5p5K0_GJorvifD-XvkFoEDOHwt0pp26tWdfM

Kariva (Desogestrel / Ethinyl estradiol): Uses, Side Effects, ...

This means that this birth control is about 99% effective at preventing pregnancy if you take it daily around the same time each day. But your chance of getting ...

5.

contraceptionjournal.org

contraceptionjournal.org/article/S0010-7824(98)00030-4/pdf

A Comprehensive Review of Desogent (Desogestrel and ...

The results of multicenter studies included in the. Desogen NDA40 demonstrated (Figure 5) only minor differences in the incidence of irregular bleeding among ...

6.

dailymed.nlm.nih.gov

dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7dbc4cdf-4ce2-5c66-343f-df381f56692a

Isibloom ® (Desogestrel and Ethinyl Estradiol Tablets, USP ...

The FDA has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral® (1 dose is 2 white pills), Alesse® ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2017/020071s025lbl.pdf

DESOGEN Tablets - accessdata.fda.gov

Patients should be counseled that this product does not protect against HIV infection. (AIDS) and other sexually transmitted diseases. DESCRIPTION. DESOGEN. ®.

8.

goodrx.com

goodrx.com/kariva/what-is?srsltid=AfmBOorMGZcG5SzdqBOUy3bMVo2c7oncH5RIsEHxKVmDpWaLq2wwZ5tr

Kariva (Desogestrel / Ethinyl estradiol): Uses, Side Effects, ...

Kariva is a combined oral contraceptive (COC) that's taken by mouth every day to prevent pregnancy. It contains 2 medications: desogestrel (a progestin) and ...