- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02531321
Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90033
- University of Southern California
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ritonavir
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.
|
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.
|
Active Comparator: Control
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.
|
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Levonorgestrel Area Under the Curve
Time Frame: 24 days
|
Levonorgestrel AUC from 0 to 72 hours
|
24 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ethinyl Estradiol Area Under the Curve
Time Frame: 24 days
|
Ethinyl estradiol area under the curve from 0 to 72 hours
|
24 days
|
Serum Progesterone Level >3ng/dL Reflecting Ovulation
Time Frame: 21 days
|
Progesterone >3ng/dL at any time during pill use
|
21 days
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Estrogens
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptives, Oral, Combined
- Contraceptives, Oral
- Contraceptive Agents, Female
- Contraceptives, Oral, Synthetic
- Contraceptives, Oral, Hormonal
- Levonorgestrel
- Estradiol
- Ethinyl Estradiol
- Ethinyl estradiol, levonorgestrel drug combination
Other Study ID Numbers
- HS-15-00112
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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