Drug InteractionPhase 4NCT01980342
Pharmacokinetics and Pharmacodynamics of the Etonogestrel Contraceptive Implant When Co-administered With Efavirenz
A Phase 4 study testing Efavirenz in people with Drug Interaction, run by Johns Hopkins University at 1 site in United States.
Trial summary
This study evaluates whether there is an interaction between etonogestrel, the progestin hormone released by the contraceptive implant Nexplanon, and efavirenz, a common medication used to treat HIV. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction
- What is being tested?
- Efavirenz
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to 4 Apr 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy women aged 18-40 years who have a Nexplanon®/Implanon® in place that is palpable on exam, had the device placed between 12 and 24 months prior to enrollment, and can provide documentation of when the implant was placed
- Able to speak and read English
- Documented HIV-negative status within 30 days of enrollment
- BMI between 18.5 and 24.9 kg/m2
- Willingness to take a two-week course of efavirenz
- Willingness to comply with study visit schedule (as described below), including blood sampling, transvaginal ultrasounds, and cervical mucus assessment
Show all 22Show fewer
- Negative urine human chorionic gonadotropin pregnancy test at study entry
- Normal laboratory values within 30 days of study entry, as specified below:
- White blood cell count ≥ 4500 and ≤ 11000 cells/mm3
- Platelet count ≥ 100,000 platelets/mm3
- Hemoglobin ≥ 8.0 g/dL
- International normalized ratio (INR) ≤ 1.8
- Aspartate transaminase (SGOT) and alanine aminotransferase (SGPT) ≤ 3 times the upper limit of normal (ULN) (upper limit of normal)
- Creatinine ≤ 1.5 x ULN
- Serum amylase ≤ 1.5 x ULN
- Total bilirubin ≤ 2.0 x ULN
- Agree to use an additional reliable method of contraception while participating in the study. Acceptable methods include:
- Abstinence
- Condoms (male or female) with or without spermicide
- Pre-existing sterilization of subject or her male partner
- Willingness to abstain from alcohol consumption during the study period
- Willingness to abstain from any grapefruit product or supplement for the duration of the study.
Who cannot join
- Breastfeeding
- Hypersensitivity to efavirenz
- History of seizure disorder
- Initiated, discontinued, or changed doses of drugs that are cytochrome P450 isoenzyme 3A4 (CYP3A4) inducers or inhibitors within 30 days of study entry.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University Bayview Medical Center
Baltimore, Maryland, 21224
About this study
This study evaluates whether there is an interaction between etonogestrel, the progestin hormone released by the contraceptive implant Nexplanon, and efavirenz, a common medication used to treat HIV. The endpoints measured in this study will help determine if such an interaction leads to decreased contraceptive efficacy of the contraceptive implant.
Read the detailed description
Women now make up nearly half of the world's HIV-infected population, and many of these women with HIV are of reproductive age. There is a growing need to provide effective contraception for those women who want or need to be protected against pregnancy. However, there is concern for decreased contraceptive efficacy in women on antiretroviral therapy who rely on hormonal contraception due to drug-drug interactions. Of particular concern is a possible interaction with etonogestrel, the active hormone in a long-acting reversible contraceptive implant. We propose a pilot study to evaluate the effect of efavirenz (EFV), a commonly used non-nucleoside reverse transcriptase inhibitor, on the pharmacokinetics of the etonogestrel implant. We will recruit 18 healthy women who have had the implant in place for 12 to 24 months. They will be asked to take a two-week course of efavirenz. During these two weeks and for four additional weeks, we will monitor semi-weekly etonogestrel concentrations, and serum, ultrasound, and cervical mucus markers of ovulation. We will also assess efavirenz concentration at baseline and at the end of the two-week treatment course. We will derive pharmacokinetic parameters and compare concentrations across time points. Results will help to inform the design of larger studies, and of similar studies with different antiretroviral medications. We hypothesize that taking efavirenz while using the etonogestrel contraceptive implant will not result in an increased incidence of ovulation.
- Conditions
- Drug Interaction
- Being tested
- Efavirenz
- Keywords
- Long acting reversible contraception, HIV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EfavirenzDrug
Also called Sustiva
Healthy women who are using Nexplanon will be asked to take a 2-week course of reduced-dose efavirenz (400 mg daily).
| Study group | Role | What they receive |
|---|---|---|
| Efavirenz | Experimental | Healthy, reproductive-age women using the etonogestrel contraceptive implant who will take a two-week course of efavirenz 400 mg orally each night. Receives: Drug: Efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Concentration of Etonogestrel Before and After Two Weeks of Efavirenz
We will draw a baseline serum etonogestrel immediately prior to a participant starting the 2-week course of efavirenz. Serial blood samples will subsequently be drawn over the next 6 weeks to assess for changes in serum etonogestrel concentration. We will be looking to see if the serum etonogestrel concentration decreases below the level necessary for reliable ovulation suppression.
Measured: 6 weeks
Secondary outcomes (4)
Serum Efavirenz Concentrations at the Start and End of the 2-week Dosing Period
We will assess serum efavirenz concentrations at the beginning and end of the 2-week dosing period. By comparing these concentrations to historical controls, we will determine whether taking efavirenz while using the etonogestrel implant alters the serum concentration of efavirenz.
Measured: 2 weeks
Serum Hormone Markers of Ovulation
We will test serial blood samples for levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and progesterone to determine whether the etonogestrel implant is able to suppress ovulation during and after a course of efavirenz.
Measured: 6 weeks
Transvaginal Ultrasound to Assess for Ovarian Follicular Development
For the entire 6 week period of the study, participants will undergo twice-weekly transvaginal ultrasound to assess for the development of ovarian follicles. This direct assessment of follicular development will be combined with serum hormone concentrations to determine if efavirenz increases the incidence of ovulation in women using the etonogestrel implant for contraception.
Measured: 6 weeks
Cervical Mucus Quality
Cervical mucus quality will be assessed twice weekly throughout the study period. The etonogestrel implant exerts a secondary contraceptive effect by causing cervical mucus to become thick and sticky, and therefore less permissive to the movement of sperm through the female genital tract. We will assess whether efavirenz causes a change in cervical mucus quality that would make sperm penetration more likely, and therefore indicate a reduction in the implant's contraceptive effect.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2013 (estimated)
- Study startOct 2014
- Primary completion4 Apr 2018
- Study completion4 Apr 2018
Why it stopped: loss of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Drug InteractionStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- American College of Obstetricians and Gynecologists, The Campbell Foundation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01980342
- Sponsor's protocol ID
- NA_00087585
- Status last verified
- May 2018
- First submitted
- 4 Nov 2013
- Last updated
- 11 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamics of the Etonogestrel Contraceptive Implant When Co-administered With Efavirenz
- ClinicalTrials.gov ID
- NCT01980342
- Acronym / sponsor ID
- NA_00087585
- Conditions
- Drug Interaction
- Keywords
- Long acting reversible contraception, HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: loss of funding
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- American College of Obstetricians and Gynecologists, The Campbell Foundation
- Study start
- Oct 2014
- Primary completion
- 4 Apr 2018 (actual)
- Study completion
- 4 Apr 2018 (actual)
- First posted
- 8 Nov 2013 (estimated)
- Results
- Posted 11 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates whether there is an interaction between etonogestrel, the progestin hormone released by the contraceptive implant Nexplanon, and efavirenz, a common medication used to treat HIV. The endpoints measured in this study will help determine if such an interaction leads to decreased contraceptive efficacy of the contraceptive implant.
Detailed description
Women now make up nearly half of the world's HIV-infected population, and many of these women with HIV are of reproductive age. There is a growing need to provide effective contraception for those women who want or need to be protected against pregnancy. However, there is concern for decreased contraceptive efficacy in women on antiretroviral therapy who rely on hormonal contraception due to drug-drug interactions. Of particular concern is a possible interaction with etonogestrel, the active hormone in a long-acting reversible contraceptive implant. We propose a pilot study to evaluate the effect of efavirenz (EFV), a commonly used non-nucleoside reverse transcriptase inhibitor, on the pharmacokinetics of the etonogestrel implant. We will recruit 18 healthy women who have had the implant in place for 12 to 24 months. They will be asked to take a two-week course of efavirenz. During these two weeks and for four additional weeks, we will monitor semi-weekly etonogestrel concentrations, and serum, ultrasound, and cervical mucus markers of ovulation. We will also assess efavirenz concentration at baseline and at the end of the two-week treatment course. We will derive pharmacokinetic parameters and compare concentrations across time points. Results will help to inform the design of larger studies, and of similar studies with different antiretroviral medications. We hypothesize that taking efavirenz while using the etonogestrel contraceptive implant will not result in an increased incidence of ovulation.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Efavirenz | Experimental | Drug: EfavirenzHealthy, reproductive-age women using the etonogestrel contraceptive implant who will take a two-week course of efavirenz 400 mg orally each night. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- Healthy women aged 18-40 years who have a Nexplanon®/Implanon® in place that is palpable on exam, had the device placed between 12 and 24 months prior to enrollment, and can provide documentation of when the implant was placed
- Able to speak and read English
- Documented HIV-negative status within 30 days of enrollment
- BMI between 18.5 and 24.9 kg/m2
- Willingness to take a two-week course of efavirenz
Key exclusion criteria (4 listed)
- Breastfeeding
- Hypersensitivity to efavirenz
- History of seizure disorder
- Initiated, discontinued, or changed doses of drugs that are cytochrome P450 isoenzyme 3A4 (CYP3A4) inducers or inhibitors within 30 days of study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EfavirenzAlso: SustivaHealthy women who are using Nexplanon will be asked to take a 2-week course of reduced-dose efavirenz (400 mg daily). | Drug | Efavirenz |
Primary outcome
Serum Concentration of Etonogestrel Before and After Two Weeks of Efavirenz
Time frame: 6 weeks
We will draw a baseline serum etonogestrel immediately prior to a participant starting the 2-week course of efavirenz. Serial blood samples will subsequently be drawn over the next 6 weeks to assess for changes in serum etonogestrel concentration. We will be looking to see if the serum etonogestrel concentration decreases below the level necessary for reliable ovulation suppression.
4 secondary outcomes
Serum Efavirenz Concentrations at the Start and End of the 2-week Dosing Period
Time frame: 2 weeks
Serum Hormone Markers of Ovulation
Time frame: 6 weeks
Transvaginal Ultrasound to Assess for Ovarian Follicular Development
Time frame: 6 weeks
Cervical Mucus Quality
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Efavirenz in people with Drug Interaction, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum Concentration of Etonogestrel Before and After Two Weeks of Efavirenz (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.