Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics

Phase 4

Terminated

• Conditions: HIV; Contraception
• Interventions: Drug: Levonorgestrel and Ethinyl Estradiol

• Registration Number: NCT02531321
• Lead Sponsor: University of Southern California

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2015-08
• Study First Submitted: 2015-08-19
• Study First Submitted QC: 2015-08-20
• Study First Posted: 2015-08-24
• Primary Completion: 2016-11
• Study Completion: 2016-11-01
• Status Verified: 2019-05
• Results First Submitted: 2019-05-07
• Results First Submitted QC: 2019-05-07
• Last Update Submitted: 2019-05-07
• Results First Posted: 2019-05-31
• Last Update Posted: 2019-05-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 17

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ritonavir	Levonorgestrel and Ethinyl Estradiol	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.
Control	Levonorgestrel and Ethinyl Estradiol	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.

Primary Outcome Measures

Name	Time	Method
Levonorgestrel Area Under the Curve	24 days	Levonorgestrel AUC from 0 to 72 hours

Secondary Outcome Measures

Name	Time	Method
Ethinyl Estradiol Area Under the Curve	24 days	Ethinyl estradiol area under the curve from 0 to 72 hours
Serum Progesterone Level >3ng/dL Reflecting Ovulation	21 days	Progesterone \>3ng/dL at any time during pill use

Trial Locations

Locations (1)

University of Southern California; 🇺🇸 Los Angeles, California, United States