HIV/AIDSPhase 2NCT03282799
Pharmacologic Strategies for the Etonogestrel Implant in HIV-Infected Women
A Phase 2 study testing etonogestrel implant in people with HIV/AIDS and Contraception, run by Catherine Anne Chappell at 1 site in Uganda.
Trial summary
This study will evaluate the frequency of ovulation and cervical mucus quality of HIV-infected Ugandan women on efavirenz-based antiretroviral therapy using either a single etonogestrel implant or two etonogestrel implants for at least one year. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- HIV/AIDS, Contraception
- What is being tested?
- etonogestrel implant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUganda
- Study dates
- 19 Feb 2019to 25 Oct 2022
- Phase
- Phase 2
- 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
- No healthy volunteers
- Adult
Who may be able to join
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Women aged 18 years to 40 years.
- Diagnosed with HIV infection.
- Medically eligible for the etonogestrel subdermal implant as a contraceptive method.
- Receiving efavirenz-based anti-retroviral therapy for a minimum of 3 months prior to screening.
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- Must agree to have concurrent highly effective non-hormonal contraception with a copper intrauterine device, if not previously medically sterilized.
- Participants must report regular menses (bleeding for 4-8 days at 21- to 35-day intervals) for the preceding 2 months.
- Participants must have a negative urine pregnancy test at entry and report no unprotected sex since the last menstrual period or in the last two weeks.
Who cannot join
- HIV RNA > 50 copies/mL at screening visit.
- Serum hemoglobin < 10.0 g/dL.
- Elevations in serum levels of alanine transaminase above 5 times the upper limit of normal.
- Elevations in serum creatinine above 2.5 times the upper limit of normal.
- Use of drugs known to be contraindicated with etonogestrel or efavirenz within 30 days of study entry. Due to the dynamic nature of drug interactions related to antiretroviral therapy, the study team will review all concomitant medications at screening for drug interactions with efavirenz and the etonogestrel implant.
- Currently pregnant or postpartum less than 30 days at study entry.
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- Breastfeeding women within 6 months of delivery.
- Use of hormonal contraception in the preceding 3 months prior to entry
- Participants determined to be ineligible for intrauterine device placement.
- Patients with a history of hypersensitivity to etonogestrel implant, undiagnosed vaginal bleeding, diagnosed or suspected sex hormone dependent neoplasia, benign or malignant liver tumor, or thromboembolic disease.
- Presence of any active clinically significant disease or life-threatening disease that, in the investigator's opinion, would compromise the subject's safety or outcome of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetic and Pharmacodynamic Evaluation of Etonogestrel Dose Escalation With Efavirenz-based Antiretroviral Therapy in HIV-infected Ugandan
This study will evaluate the frequency of ovulation and cervical mucus quality of HIV-infected Ugandan women on efavirenz-based antiretroviral therapy using either a single etonogestrel implant or two etonogestrel implants for at least one year.
Read the detailed description
This study is being done to compare the rate of ovulation when women receive two subdermal implant contraception devices containing the hormone etonogestrel (instead of only one device) while taking the HIV drug efavirenz. The etonogestrel implant is a device that is inserted under the skin on the upper arm and releases a small amount of drug into the body every day over a long period of time to prevent pregnancy for 3 years. A total of 72 non-pregnant women in Uganda, who agree to use the copper intrauterine device throughout the study, will participate in this study. Half will be assigned by chance to use one implant and half will be assigned to use two implants at the entry visit. After the entry visit to place the implant, visits will be scheduled 1 week, 4 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 21 weeks, 22, weeks, 23 weeks, 24 weeks, 36 weeks, 45 weeks, 46 weeks, 47 weeks, and 48 weeks after the implant(s) were placed. The rate of ovulation (determined by weekly endogenous progesterone concentrations in the blood during months 3, 6, and 12) will be compared between women that receive two 68 mg etonogestrel implants compared to one 68 mg etonogestrel implant in combination with efavirenz-based antiretroviral therapy. Cervical mucus quality (from cervical mucus samples collected weekly at months 3, 6, and 12), the blood concentration of etonogestrel (from blood samples collected at day 3 and weeks 1, 4, 12, 24, 36, 48) and efavirenz (from blood samples collected at enrollment and weeks 4, 12, 24, 36, 48, and the number of adverse events deemed related to etonogestrel implant use through 48 weeks will also be compared between the one- and two-implant study arms.
- Conditions
- HIV/AIDS, Contraception
- Being tested
- etonogestrel implant
- Keywords
- etonogestrel, efavirenz, antiretroviral therapy, HIV
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etonogestrel implantDrug
Also called Nexplanon, Implanon
The etonogestrel implant is an contraceptive implant that is placed into the upper arm.
| Study group | Role | What they receive |
|---|---|---|
| Standard Dose Etonogestrel Implant | Active comparator | Single 68 mg etonogestrel implant Receives: Drug: etonogestrel implant |
| Increased Dose Etonogestrel Implant | Experimental | Two 68 mg (136 mg total) etonogestrel implants Receives: Drug: etonogestrel implant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants That Ovulate During Month 3
Proportion of participants that experience at least one ovulation during month 3 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 3 (weeks 9-12). Ovulation is defined as endogenous progesterone concentrations of >3 ng/mL.
Measured: 3 months
Proportion of Participants That Ovulate During Month 6
Proportion of participants that experience at least one ovulation during month 6 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 6 (weeks 21-24). Ovulation is defined as endogenous progesterone concentrations of >3 ng/mL.
Measured: 6 months
Proportion of Participants That Ovulate During Month 12
Proportion of participants that experience at least one ovulation during month 12 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 12 (weeks 45-48). Ovulation is defined as endogenous progesterone concentrations of >3 ng/mL.
Measured: 12 months
Secondary outcomes (13)
Proportion of Cervical Mucus Scores Greater Than 10
The proportion of World Health Organization cervical mucus scores that are greater than 10 from weekly samples collected during months 3, 6 and 12 of etonogestrel implant use. A cervical mucus score greater than 10 indicates the mucus is favorable for sperm penetration or lack of contraceptive effect. The cervical mucus score ranges from 0 indicating least favorable for sperm penetration to 15 for most favorable for sperm penetration.
Measured: 12 months
Median Efavirenz Concentration at Enrollment
Median efavirenz concentrations measured in plasma samples collected at enrollment, prior to insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Measured: Day 0
Median Efavirenz Concentration at Week 4
Median efavirenz concentrations measured in plasma samples collected 4 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Measured: 4 weeks
Median Efavirenz Concentration at Week 12
Median efavirenz concentrations measured in plasma samples collected 12 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Measured: 12 weeks
Median Efavirenz Concentration at Week 24
Median efavirenz concentrations measured in plasma samples collected 24 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Measured: 24 weeks
Median Efavirenz Concentration at Week 36
Median efavirenz concentrations measured in plasma samples collected 36 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Measured: 36 weeks
Median Efavirenz Concentration at Week 48
Median efavirenz concentrations measured in plasma samples collected 48 weeks after insertion of the etonogestrel implant(s). Plasma efavirenz concentrations were quantified using a high-performance liquid chromatography assay with ultraviolet detection.
Measured: 48 weeks
Median Etonogestrel Concentration at Week 1
Median etonogestrel concentrations measured in plasma samples collected 1 week after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Measured: 1 week
Median Etonogestrel Concentration at Week 4
Median etonogestrel concentrations measured in plasma samples collected 4 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Measured: 4 weeks
Median Etonogestrel Concentration at Week 12
Median etonogestrel concentrations measured in plasma samples collected 12 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Measured: 12 weeks
Median Etonogestrel Concentration at Week 24
Median etonogestrel concentrations measured in plasma samples collected 24 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Measured: 24 weeks
Median Etonogestrel Concentration at Week 36
Median etonogestrel concentrations measured in plasma samples collected 36 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Measured: 36 weeks
Median Etonogestrel Concentration at Week 48
Median etonogestrel concentrations measured in plasma samples collected 48 weeks after insertion of the etonogestrel implant(s). Plasma etonogestrel concentrations were quantified using liquid chromatography tandem mass spectrometry.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2017
- Study start19 Feb 2019
- Primary completion22 Dec 2020
- Study completion25 Oct 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Anne Chappell
- Sponsor type
- University, hospital or other
- Collaborators
- Infectious Disease Institute, Kampala, Uganda, University of Nebraska
- Responsible party
- Sponsor-investigator, Catherine Anne Chappell, University of Pittsburgh
- Investigators
- Catherine A Chappell, MD MSc, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03282799
- Sponsor's protocol ID
- PRO17080453
- Status last verified
- Aug 2024
- First submitted
- 12 Sep 2017
- Last updated
- 5 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chappell CA, Lamorde M, Nakalema S, Kyohairwe I, Byakika-Kibwika P, Meyn LA, Pham MM, Scarsi KK. A randomized trial of double vs single-dose etonogestrel implant to overcome the interaction with efavirenz-based antiretroviral therapy. Am J Obstet Gynecol. 2024 Aug;231(2):242.e1-242.e9. doi: 10.1016/j.ajog.2024.03.001. Epub 2024 Mar 7.
PubMed 38458408
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic and Pharmacodynamic Evaluation of Etonogestrel Dose Escalation With Efavirenz-based Antiretroviral Therapy in HIV-infected Ugandan
- ClinicalTrials.gov ID
- NCT03282799
- Acronym / sponsor ID
- PRO17080453
- Conditions
- HIV/AIDS, Contraception
- Keywords
- etonogestrel, efavirenz, antiretroviral therapy, HIV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Catherine Anne ChappellUniversity, hospital or other
- Collaborators
- Infectious Disease Institute, Kampala, Uganda, University of Nebraska
- Study start
- 19 Feb 2019 (actual)
- Primary completion
- 22 Dec 2020 (actual)
- Study completion
- 25 Oct 2022 (actual)
- First posted
- 14 Sep 2017 (actual)
- Results
- Posted 5 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the frequency of ovulation and cervical mucus quality of HIV-infected Ugandan women on efavirenz-based antiretroviral therapy using either a single etonogestrel implant or two etonogestrel implants for at least one year.
Detailed description
This study is being done to compare the rate of ovulation when women receive two subdermal implant contraception devices containing the hormone etonogestrel (instead of only one device) while taking the HIV drug efavirenz. The etonogestrel implant is a device that is inserted under the skin on the upper arm and releases a small amount of drug into the body every day over a long period of time to prevent pregnancy for 3 years. A total of 72 non-pregnant women in Uganda, who agree to use the copper intrauterine device throughout the study, will participate in this study. Half will be assigned by chance to use one implant and half will be assigned to use two implants at the entry visit. After the entry visit to place the implant, visits will be scheduled 1 week, 4 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 21 weeks, 22, weeks, 23 weeks, 24 weeks, 36 weeks, 45 weeks, 46 weeks, 47 weeks, and 48 weeks after the implant(s) were placed. The rate of ovulation (determined by weekly endogenous progesterone concentrations in the blood during months 3, 6, and 12) will be compared between women that receive two 68 mg etonogestrel implants compared to one 68 mg etonogestrel implant in combination with efavirenz-based antiretroviral therapy. Cervical mucus quality (from cervical mucus samples collected weekly at months 3, 6, and 12), the blood concentration of etonogestrel (from blood samples collected at day 3 and weeks 1, 4, 12, 24, 36, 48) and efavirenz (from blood samples collected at enrollment and weeks 4, 12, 24, 36, 48, and the number of adverse events deemed related to etonogestrel implant use through 48 weeks will also be compared between the one- and two-implant study arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Dose Etonogestrel Implant | Active comparator | Drug: etonogestrel implantSingle 68 mg etonogestrel implant |
| Increased Dose Etonogestrel Implant | Experimental | Drug: etonogestrel implantTwo 68 mg (136 mg total) etonogestrel implants |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Women aged 18 years to 40 years.
- Diagnosed with HIV infection.
- Medically eligible for the etonogestrel subdermal implant as a contraceptive method.
Key exclusion criteria (11 listed)
- HIV RNA > 50 copies/mL at screening visit.
- Serum hemoglobin < 10.0 g/dL.
- Elevations in serum levels of alanine transaminase above 5 times the upper limit of normal.
- Elevations in serum creatinine above 2.5 times the upper limit of normal.
- Use of drugs known to be contraindicated with etonogestrel or efavirenz within 30 days of study entry. Due to the dynamic nature of drug interactions related to antiretroviral therapy, the study team will review all concomitant medications at screening for drug interactions with efavirenz and the etonogestrel implant.
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 |
|---|---|---|
| etonogestrel implantAlso: Nexplanon, ImplanonThe etonogestrel implant is an contraceptive implant that is placed into the upper arm. | Drug | Increased Dose Etonogestrel Implant, Standard Dose Etonogestrel Implant |
Primary outcome
Proportion of Participants That Ovulate During Month 3
Time frame: 3 months
Proportion of participants that experience at least one ovulation during month 3 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 3 (weeks 9-12). Ovulation is defined as endogenous progesterone concentrations of >3 ng/mL.
Proportion of Participants That Ovulate During Month 6
Time frame: 6 months
Proportion of participants that experience at least one ovulation during month 6 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 6 (weeks 21-24). Ovulation is defined as endogenous progesterone concentrations of >3 ng/mL.
Proportion of Participants That Ovulate During Month 12
Time frame: 12 months
Proportion of participants that experience at least one ovulation during month 12 of etonogestrel implant use. Serum progesterone concentrations are measured weekly during month 12 (weeks 45-48). Ovulation is defined as endogenous progesterone concentrations of >3 ng/mL.
13 secondary outcomes
Proportion of Cervical Mucus Scores Greater Than 10
Time frame: 12 months
Median Efavirenz Concentration at Enrollment
Time frame: Day 0
Median Efavirenz Concentration at Week 4
Time frame: 4 weeks
Median Efavirenz Concentration at Week 12
Time frame: 12 weeks
Median Efavirenz Concentration at Week 24
Time frame: 24 weeks
Median Efavirenz Concentration at Week 36
Time frame: 36 weeks
Median Efavirenz Concentration at Week 48
Time frame: 48 weeks
Median Etonogestrel Concentration at Week 1
Time frame: 1 week
Median Etonogestrel Concentration at Week 4
Time frame: 4 weeks
Median Etonogestrel Concentration at Week 12
Time frame: 12 weeks
Median Etonogestrel Concentration at Week 24
Time frame: 24 weeks
Median Etonogestrel Concentration at Week 36
Time frame: 36 weeks
Median Etonogestrel Concentration at Week 48
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38458408Chappell CA, Lamorde M, Nakalema S, Kyohairwe I, Byakika-Kibwika P, Meyn LA, Pham MM, Scarsi KK. A randomized trial of double vs single-dose etonogestrel implant to overcome the interaction with efavirenz-based antiretroviral therapy. Am J Obstet Gynecol. 2024 Aug;231(2):242.e1-242.e9. doi: 10.1016/j.ajog.2024.03.001. Epub 2024 Mar 7.
- 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.
Catherine A Chappell, MD MSc principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing etonogestrel implant in people with HIV/AIDS and Contraception, run by Catherine Anne Chappell at 1 site in Uganda.
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 9 inclusion and 11 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: finished, as of the sponsor's last update on 5 Sep 2024. 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 Uganda. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 5 Sep 2024). 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?
Proportion of Participants That Ovulate During Month 3 (time frame: 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03282799, which also lists 1 linked publication.
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 5 Sep 2024.