Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics

NCT ID: NCT02531321

Last Updated: 2019-05-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2016-11-01

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.

Conditions

Contraception; HIV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Levonorgestrel and Ethinyl Estradiol

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Levonorgestrel and Ethinyl Estradiol

Intervention Type: DRUG

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.

Interventions

Levonorgestrel and Ethinyl Estradiol

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Nicole Bender

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Southern California

Los Angeles, California, United States

Countries

United States

Other Identifiers

HS-15-00112

Identifier Type: -

Identifier Source: org_study_id