Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics

May 7, 2019 updated by: Nicole Bender, University of Southern California

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

Terminated

Conditions

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.

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

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Actual)

November 1, 2016

Study Completion (Actual)

November 1, 2016

Study Registration Dates

First Submitted

August 19, 2015

First Submitted That Met QC Criteria

August 20, 2015

First Posted (Estimate)

August 24, 2015

Study Record Updates

Last Update Posted (Actual)

May 31, 2019

Last Update Submitted That Met QC Criteria

May 7, 2019

Last Verified

May 1, 2019

More Information

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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