Clinical trial NCT02531321: Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics
Official title: Effects of Protease Inhibitor Use on Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics in HIV-positive Women
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Contraception
HIV
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2015-08-24
Enrollment: 17
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: 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

Primary outcomes:
measure: Levonorgestrel Area Under the Curve
timeFrame: 24 days
Secondary outcomes:
measure: Ethinyl Estradiol Area Under the Curve
timeFrame: 24 days
measure: Serum Progesterone Level >3ng/dL Reflecting Ovulation
timeFrame: 21 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
Study officials:
References: