ContraceptionPhase 4NCT02531321
Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics
A Phase 4 study testing Levonorgestrel and Ethinyl Estradiol in people with Contraception and HIV, run by University of Southern California at 1 site in United States.
Trial summary
The project is a two-arm prospective cohort and pharmacokinetic study comparing levonorgestrel and ethinyl estradiol pharmacokinetics in HIV-positive women taking antiretroviral regimens that include ritonavir to those in women who take regimens known not to interact with combined oral contraceptives. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Contraception, HIV
- What is being tested?
- Levonorgestrel and Ethinyl Estradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2015to 1 Nov 2016
- 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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- HIV positive
- Female
- Age 18-45
- Using any of the following medication regimens: no ARV medication, entry inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), integrase inhibitors, and CCR5 agonists. Acceptable NRTI combinations include zidovudine (ZDV), lamivudine (3TC), emtricitabine (FTC), didanosine (ddl), stavudine (d4T), abacavir (ABC), and tenofovir disoproxil fumarate (TDF)
- Ovulatory (mid-luteal progesterone >3ng/dL)
- Not planning to conceive during the study period
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- Willing to abstain from grapefruit products
- If taking ritonavir, willing to use alternate non-hormonal contraception
- BMI < or = 40
- Able to consent in English or Spanish
- No change in medication regimen for at least 21 days prior to study entry and no planned change during the study period
- CD4 > or =200, and/or not considered profoundly immuncompromised by primary HIV provider
Who cannot join
- Using on the combination of ZDV at d4T
- Platelets <50,000
- AST or ALT > twice upper limit of normal
- Bilirubin > twice upper limit of normal
- Use of other CYP3A4 inducing or inhibiting medications
- Pregnant or breastfeeding in last 30 days
Show all 14Show fewer
- Use of DepoProvera in last 180 days
- Use of any other hormonal contraception in last 30 days
- Undiagnosed vaginal bleeding or invasive cancer of the reproductive tract
- ->50% change in tobacco use in the last month
- Initiation or titration of methadone therapy in the last month
- Uncontrolled thyroid disease
- Contraindication to estrogen use
- Inability to comply with study protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California
Los Angeles, California, 90033
About this study
Official title: Effects of Protease Inhibitor Use on Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics in HIV-positive Women
The project is a two-arm prospective cohort and pharmacokinetic study comparing levonorgestrel and ethinyl estradiol pharmacokinetics in HIV-positive women taking antiretroviral regimens that include ritonavir to those in women who take regimens known not to interact with combined oral contraceptives. In addition, the prevalence of ovulation will be measured in each group. Participants will take a combined oral contraceptive containing levonorgestrel and ethinyl estradiol for 21 days, during which they will undergo twice-weekly serum progesterones. On the final day, they will complete a pharmacokinetic study. The investigators hypothesize that levonorgestrel levels, as measured by area-under-the-curve from 0 to 72 hours, will be increased in women on ritonavir, while ethinyl estradiol levels will be decreased and ovulation, defined by a serum progesterone of at least 3 ng/mL, will be unchanged.
This study will be the first to evaluate the effects of ritonavir on the pharmacokinetics of a combined oral contraceptive containing the progestin levonorgestrel. In addition, no previous studies have rigorously assessed ovulation in women taking protease inhibitors and combined oral contraceptives. As a result, this study will provide new information correlating pharmacokinetic changes with effects on ovulation.
- Conditions
- Contraception, HIV
- Being tested
- Levonorgestrel and Ethinyl Estradiol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levonorgestrel and Ethinyl EstradiolDrug
All participants will take a combined oral contraceptive containing 150mcg levonorgestrel and 30mcg ethinyl estradiol for 21 days. Pharmacokinetics and pharmacodynamics will be compared between participants using antiretroviral regimens including ritonavir-boosted protease inhibitors and those using regimens that do not interact with oral contraceptives.
| Study group | Role | What they receive |
|---|---|---|
| Ritonavir | Experimental | Participants taking antiretroviral regimens including ritonavir-boosted protease inhibitors will take a combined oral contraceptive containing 150mcg levonorgestrel and 30mcg ethinyl estradiol for 21 days. Receives: Drug: Levonorgestrel and Ethinyl Estradiol |
| Control | Active comparator | Participants taking antiretroviral regimens known not to interact with oral contraceptives will take a combined oral contraceptive containing 150mcg levonorgestrel and 30mcg ethinyl estradiol for 21 days. Receives: Drug: Levonorgestrel and Ethinyl Estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levonorgestrel Area Under the Curve
Levonorgestrel AUC from 0 to 72 hours
Measured: 24 days
Secondary outcomes (2)
Ethinyl Estradiol Area Under the Curve
Ethinyl estradiol area under the curve from 0 to 72 hours
Measured: 24 days
Serum Progesterone Level >3ng/dL Reflecting Ovulation
Progesterone >3ng/dL at any time during pill use
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2015 (estimated)
- Study startAug 2015
- Primary completionNov 2016
- Study completion1 Nov 2016
Why it stopped: Difficulty recruiting
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 ContraceptionStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicole Bender, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02531321
- Sponsor's protocol ID
- HS-15-00112
- Status last verified
- May 2019
- First submitted
- 19 Aug 2015
- Last updated
- 31 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Protease Inhibitor Use on Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics in HIV-positive Women
- ClinicalTrials.gov ID
- NCT02531321
- Acronym / sponsor ID
- HS-15-00112
- Conditions
- Contraception, HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty recruiting
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- Nov 2016 (actual)
- Study completion
- 1 Nov 2016 (actual)
- First posted
- 24 Aug 2015 (estimated)
- Results
- Posted 31 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The project is a two-arm prospective cohort and pharmacokinetic study comparing levonorgestrel and ethinyl estradiol pharmacokinetics in HIV-positive women taking antiretroviral regimens that include ritonavir to those in women who take regimens known not to interact with combined oral contraceptives. In addition, the prevalence of ovulation will be measured in each group. Participants will take a combined oral contraceptive containing levonorgestrel and ethinyl estradiol for 21 days, during which they will undergo twice-weekly serum progesterones. On the final day, they will complete a pharmacokinetic study. The investigators hypothesize that levonorgestrel levels, as measured by area-under-the-curve from 0 to 72 hours, will be increased in women on ritonavir, while ethinyl estradiol levels will be decreased and ovulation, defined by a serum progesterone of at least 3 ng/mL, will be unchanged.
This study will be the first to evaluate the effects of ritonavir on the pharmacokinetics of a combined oral contraceptive containing the progestin levonorgestrel. In addition, no previous studies have rigorously assessed ovulation in women taking protease inhibitors and combined oral contraceptives. As a result, this study will provide new information correlating pharmacokinetic changes with effects on ovulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ritonavir | Experimental | Drug: Levonorgestrel and Ethinyl EstradiolParticipants taking antiretroviral regimens including ritonavir-boosted protease inhibitors will take a combined oral contraceptive containing 150mcg levonorgestrel and 30mcg ethinyl estradiol for 21 days. |
| Control | Active comparator | Drug: Levonorgestrel and Ethinyl EstradiolParticipants taking antiretroviral regimens known not to interact with oral contraceptives will take a combined oral contraceptive containing 150mcg levonorgestrel and 30mcg ethinyl estradiol for 21 days. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- HIV positive
- Female
- Age 18-45
- Using any of the following medication regimens: no ARV medication, entry inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), integrase inhibitors, and CCR5 agonists. Acceptable NRTI combinations include zidovudine (ZDV), lamivudine (3TC), emtricitabine (FTC), didanosine (ddl), stavudine (d4T), abacavir (ABC), and tenofovir disoproxil fumarate (TDF)
- Ovulatory (mid-luteal progesterone >3ng/dL)
Key exclusion criteria (14 listed)
- Using on the combination of ZDV at d4T
- Platelets <50,000
- AST or ALT > twice upper limit of normal
- Bilirubin > twice upper limit of normal
- Use of other CYP3A4 inducing or inhibiting medications
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 |
|---|---|---|
| Levonorgestrel and Ethinyl EstradiolAll participants will take a combined oral contraceptive containing 150mcg levonorgestrel and 30mcg ethinyl estradiol for 21 days. Pharmacokinetics and pharmacodynamics will be compared between participants using antiretroviral regimens including ritonavir-boosted protease inhibitors and those using regimens that do not interact with oral contraceptives. | Drug | Control, Ritonavir |
Primary outcome
Levonorgestrel Area Under the Curve
Time frame: 24 days
Levonorgestrel AUC from 0 to 72 hours
2 secondary outcomes
Ethinyl Estradiol Area Under the Curve
Time frame: 24 days
Serum Progesterone Level >3ng/dL Reflecting Ovulation
Time frame: 21 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 Levonorgestrel and Ethinyl Estradiol in people with Contraception and HIV, run by University of Southern California 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 12 inclusion and 14 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 31 May 2019. 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 31 May 2019). 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?
Levonorgestrel Area Under the Curve (time frame: 24 days). 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 31 May 2019.