Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics

NCT02531321 | Terminated Phase 4 Results

• 1 other identifier: HS-15-00112
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Levonorgestrel Area Under the Curve

  Levonorgestrel AUC from 0 to 72 hours

  24 days

Secondary Outcomes (2)

• Ethinyl Estradiol Area Under the Curve

  24 days

• Serum Progesterone Level >3ng/dL Reflecting Ovulation

  21 days

Study Arms (2)

Ritonavir

EXPERIMENTAL

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.

Drug: Levonorgestrel and Ethinyl Estradiol

Control

ACTIVE COMPARATOR

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.

Drug: Levonorgestrel and Ethinyl Estradiol

Interventions

Levonorgestrel and Ethinyl Estradiol 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; Ritonavir

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

University of Southern California

Los Angeles, California, 90033, United States

Location

MeSH Terms

Interventions

ethinyl estradiol, levonorgestrel drug combination

Results Point of Contact

• Title: Dr. Nicole Bender
• Organization: University of Southern California

nicole.bender@med.usc.edu

3234093416

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 19, 2015
• First Posted: August 24, 2015
• Study Start: August 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: May 31, 2019
• Results First Posted: May 31, 2019

Record last verified: 2019-05

Locations

US (1)