Contraceptive Pills for Discontinuing Implants

Overseen By Jeanelle Sheeder, PhD

Age: < 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: Etonogestrel implant

Must not be taking: Estrogen birth control

Disqualifiers: Pregnancy desire, Moving plans, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 months

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether providing individuals who recently started using an etonogestrel implant (a type of birth control) with a supply of oral contraceptive pills (Ethinyl Estradiol / Norgestimate) can better manage unwanted bleeding compared to standard advice and care. The aim is to determine if the pills increase the likelihood of continued implant use. Participants will be divided into two groups: one receives the pills and a plan for managing bleeding, while the other receives regular counseling. Individuals aged 14 to 22 who have just started using the implant for the first time may be suitable candidates. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand its benefits for more patients, offering an opportunity to contribute to valuable research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What is the safety track record for Ethinyl Estradiol / Norgestimate Oral Tablet?

Research has shown that the combination of ethinyl estradiol and norgestimate, common ingredients in birth control pills, is generally safe. The FDA has approved these pills as effective for preventing pregnancy, confirming their thorough testing for safety and effectiveness.

Studies indicate that most people tolerate these pills well. Common side effects may include nausea, headaches, or spotting between periods. Serious side effects are rare, but it is important to be aware of them, such as an increased risk of blood clots, especially for smokers or those over 35.

Overall, these pills have a strong safety record, particularly for those without specific health conditions that could cause issues. Prospective trial participants or those considering this medication should discuss their health history with a healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the use of Ethinyl Estradiol/Norgestimate oral tablets for managing bothersome bleeding in individuals discontinuing contraceptive implants because it offers a targeted approach to an often frustrating side effect. Unlike the standard care options, which primarily involve monitoring or contraceptive implant removal, this treatment provides a proactive solution by using a specific protocol of combined oral contraceptive pills. The treatment combines 35mcg ethinyl estradiol with norgestimate, which is known for its efficacy in regulating menstrual cycles. This combination could help stabilize bleeding patterns more effectively than current methods, making it a potentially valuable option for those experiencing this common issue.

What evidence suggests that this trial's treatments could be effective for implant discontinuation?

Research has shown that the combination of ethinyl estradiol and norgestimate effectively reduces breakthrough bleeding, a common issue with contraceptive implants. In this trial, participants in the COCR arm will receive this combination to address bothersome bleeding. Studies found that the occurrence of breakthrough bleeding or spotting decreased over time for users of this pill, from 16.3% at the beginning to 7.7% after a year. This indicates that most users experienced less bleeding as they continued taking the pills. The pills work best when taken exactly as directed, which is crucial for maximum effectiveness. This treatment is already approved and widely used for other conditions, demonstrating its effectiveness in managing contraceptive side effects. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for young individuals aged 14 to 22.9 who are using the etonogestrel implant as a contraceptive for the first time. It's not suitable for those with estrogen-related contraindications, plans to move away within a year, or a desire to become pregnant in the next year.

Inclusion Criteria

You are between ages of 14 to 22.9 years

Started etonogestrel implant for the first time and have never used the implant before

Exclusion Criteria

There is any contraindication to estrogen containing birth control

Plans to move from the area in next 12 months and is not able to come to the clinic

You plan to become pregnant within the next year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard counseling or the COCR intervention, which includes advance provision of combined oral contraceptive pills and a bleeding rescue regimen

12 months

Regular follow-ups as needed

Follow-up

Participants are monitored for satisfaction with the contraceptive implant and healthcare interactions related to the implant

12 months

3 visits (in-person) at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ethinyl Estradiol / Norgestimate Oral Tablet

Trial Overview

The study tests if giving out combined oral contraceptive pills (COCs) and a bleeding rescue regimen alongside standard counseling reduces premature discontinuation of contraceptive implants compared to just counseling alone.

How Is the Trial Designed?

Group I: COCR Arm Experimental Treatment 1 Intervention

Participants in the COCR arm will receive three packs of combined oral contraceptive pills (35mcg ethinyl estradiol/norgestimate) and a specific protocol for their use for bothersome bleeding.

Group II: SOC Arm Active Control 1 Intervention

Participants in the SC arm will be offered care according to our standardized protocol, which may include STI testing, reassurance and monitoring, prescription of COCs if desired, or removal.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

In a study of 300 women comparing two oral contraceptives, Brevicon users experienced significantly more intermenstrual bleeding than those using Norinyl 1/35, which could influence their choice to continue using the method.

Despite the differences in side effects, both contraceptives had high discontinuation rates after 11 months, with 68.2% for Norinyl 1/35 and 75.2% for Brevicon, primarily due to menstrual problems and other personal reasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative clinical trial of Norinyl 1/35 versus Brevicon in Rio Clara, Brazil. Albuquerque, LA., Albuquerque, EG., Waszak, CS., et al.[2019]

In a study involving 19 healthy women, raltegravir did not significantly affect the pharmacokinetics of the estrogen and progestin components of the oral contraceptive norgestimate-ethinyl estradiol, indicating that it can be safely co-administered without requiring dose adjustments.

The study found that co-administration of raltegravir and the contraceptive was well tolerated, with no serious adverse effects reported, suggesting a favorable safety profile for this combination in HIV-infected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women. Anderson, MS., Hanley, WD., Moreau, AR., et al.[2021]

Cyclessa, a new low-dose triphasic contraceptive, demonstrated comparable contraceptive efficacy to Ortho-Novum 7/7/7 while providing significantly better cycle control, including fewer instances of breakthrough bleeding and spotting.

Women using Cyclessa experienced less weight gain and a smaller increase in body mass index compared to those using Ortho-Novum 7/7/7, indicating a favorable safety profile for Cyclessa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, cycle control, and safety of two triphasic oral contraceptives: Cyclessa (desogestrel/ethinyl estradiol) and ortho-Novum 7/7/7 (norethindrone/ethinyl estradiol): a randomized clinical trial. Kaunitz, AM.[2019]

In a large study of 59,701 women over 342,348 menstrual cycles, the oral contraceptive norgestimate/ethinyl estradiol demonstrated a very low use-efficacy Pearl index of 0.25 pregnancies per 100 woman-years, indicating high effectiveness in preventing pregnancy.

The contraceptive was well-tolerated, with minimal side effects and significant reductions in bleeding intensity for 32% of women, while only 1% experienced amenorrhea and low rates of spotting (4%) and breakthrough bleeding (3%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open, multicenter study of 59,701 women. Runnebaum, B., Grunwald, K., Rabe, T.[2022]

The contraceptive patch (Ortho Evra) delivers consistent levels of norelgestromin and ethinyl estradiol, maintaining effective hormone concentrations for up to 10 days, even if a scheduled change is missed for two days.

The patch's pharmacokinetics are stable across different application sites and conditions, such as heat and exercise, and do not interact with tetracycline, ensuring reliable contraceptive efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic overview of Ortho Evra/Evra. Abrams, LS., Skee, D., Natarajan, J., et al.[2019]

Both monophasic and triphasic formulations of ethinyl estradiol plus norgestimate have been shown to provide effective contraception, with efficacy comparable to other oral contraceptives, based on numerous clinical studies.

Both formulations demonstrated favorable metabolic effects, such as increasing good cholesterol (HDL) and reducing the LDL/HDL ratio, while showing minimal impact on weight gain, blood pressure, and carbohydrate metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a monophasic and a triphasic oral contraceptive containing norgestimate. Corson, SL.[2019]

The study analyzed the plasma concentration profiles of three oral contraceptive steroid preparations in Egyptian women, finding that peak plasma concentrations of the estrogen component (EE2) varied significantly among the preparations, with Ovral showing the highest levels.

Despite differences in estrogen content, the pharmacokinetic parameters such as half-life, oral clearance, and volume of distribution were similar across the contraceptives, indicating that the kinetic profiles in healthy Egyptian women are comparable to those in other ethnic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of oral contraceptive steroids in Egyptian women: studies with Ovral, Nordette and Norminest. el-Raghy, I., Back, DJ., Makeram, M., et al.[2019]

Norgestimate/ethinyl estradiol, a new oral contraceptive, shows excellent contraceptive efficacy with a Pearl index of 0.25, indicating a very low failure rate.

This contraceptive has a low impact on carbohydrate and lipid metabolism and does not significantly affect blood coagulation factors, suggesting a potentially lower risk of cardiovascular disease compared to other oral contraceptives, although caution is advised for patients with a history of vascular or thrombotic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Norgestimate: a clinical overview of a new progestin. Bringer, J.[2019]

Norgestimate combined with ethinyl estradiol is an effective low-dose oral contraceptive that offers cycle control similar to older formulations while having low androgenic activity, as confirmed by several phase II and III clinical studies.

This combination has been shown to improve lipid profiles by increasing high-density lipoprotein cholesterol and enhancing the low-density/high-density lipoprotein ratio, unlike norgestrel, which has adverse effects on these lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A norgestimate-containing oral contraceptive: review of clinical studies. Kafrissen, ME.[2019]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/12814811/

Efficacy, safety and cycle control of five oral contraceptive ...

Breakthrough bleeding and/or spotting (BBS; % total cycles) was 17.2% for ORTHO TRI-CYCLEN Lo and 14.4% for ORTHO TRI-CYCLEN. The mean number of days of BBS/ ...

2.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2013/019653Orig1s046,%20019697Orig1s042lbl.pdf

TABLETS (norgestimate/ethinyl estradiol) and ORTHO-CYCLEN

To achieve maximum contraceptive effectiveness, ORTHO TRI-CYCLEN®. Tablets and ORTHO-CYCLEN® Tablets must be taken exactly as directed and at intervals not ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0010782406003283

Combined hormonal contraceptive trials: variable data ...

Combined hormonal contraceptive trials: variable data collection and bleeding assessment methodologies influence study outcomes and physician perception☆,.

4.

researchgate.net

researchgate.net/publication/11679217_Comparison_of_a_novel_norgestimateethinyl_estradiol_oral_contraceptive_Ortho_Tri-Cyclen_Lo_with_the_oral_contraceptive_Loestrin_Fe_120

Comparison of a novel norgestimate/ethinyl estradiol oral ...

At representative Cycles 1, 3, 6, 9, and 13, breakthrough bleeding and spotting rates were 16.3, 11.5, 10.3, 7.9, and 7.7%, respectively, in the ...

5.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2005/021690s000_PRNTLBL.pdf

ortho tri-cyclen® tablets

Norgestimate, in combination with ethinyl estradiol, does not counteract the estrogen-induced increases in sex hormone binding globulin (SHBG), resulting in ...

6.

rxlist.com

rxlist.com/ortho-tri-cyclen-drug.htm

Ortho Tri-Cyclen - norgestimate and ethinyl estradiol

ORTHO TRI-CYCLEN is indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral ...

7.

mayoclinic.org

mayoclinic.org/drugs-supplements/ethinyl-estradiol-and-norgestimate-oral-route/description/drg-20061380

Ethinyl estradiol and norgestimate (oral route)

It is a birth control pill that contains two types of hormones, ethinyl estradiol and norgestimate, and when taken properly, prevents pregnancy.

8.

drugs.com

drugs.com/ppa/ethinyl-estradiol-and-norgestimate.html

Ethinyl Estradiol and Norgestimate

Menstrual bleeding (menorrhagia). Based on the American College of Obstetricians and Gynecologists Practice Bulletin on Noncontraceptive Uses of ...

9.

reference.medscape.com

reference.medscape.com/drug/mononessa-ortho-cyclen-norgestimate-ethinyl-estradiol-342754

norgestimate/ethinyl estradiol (Rx)

1 hormonally active tablet daily for 21 days, then 1 inert tablet daily for 7 days; cycle repeated; start Sunday after onset of menstruation.