Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics

HIV Clinical Trial

Official title:

Effects of Protease Inhibitor Use on Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics in HIV-positive Women

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02531321
• Other study ID #: HS-15-00112
• Status: Terminated
• Phase: Phase 4
• Start date: August 2015
• Est. completion date: November 1, 2016

Study information

• Verified date: May 2019
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: November 1, 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Contraception
• HIV

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Levonorgestrel Area Under the Curve	Levonorgestrel AUC from 0 to 72 hours	24 days
Secondary	Ethinyl Estradiol Area Under the Curve	Ethinyl estradiol area under the curve from 0 to 72 hours	24 days
Secondary	Serum Progesterone Level >3ng/dL Reflecting Ovulation	Progesterone >3ng/dL at any time during pill use	21 days