AIDS Clinical Trials Group- Chair Support for Protocol A5316

Project: Research project

Project Details

Description

A5316 is a phase II, open-label, non-randomized, steady-state, parallel design trial to evaluate pharmacokinetic (PK) interactions between hormonal contraception (etonogestrel and ethinyl estradiol) delivered via a vaginal ring and efavirenz (EFV) or atazanavir/ritonavir (ATV/r) based regimens in HIV-infected women.

There will be three study groups of HIV-infected women using the vaginal ring. Those receiving:
• No antiretroviral therapy (ART)
• EFV 600 mg daily with two or more nucleoside/tide reverse transcriptase inhibitors (NRTIs), or
• ATV 300 mg with ritonavir 100 mg daily with tenofovir disoproxil fumarate (TDF) and one or more additional NRTIs

Blood samples for ART PK analysis will be collected before and after vaginal ring placement in the same women.

The study will enroll 75 HIV-infected, non-pregnant women ≥16 years old interested in using the vaginal ring (NuvaRing), either on a targeted ART regimen as listed below or not on ART: 25 who are not taking ART (control group); 25 who are taking EFV-based regimens; and 25 who are taking ATV/r-based regimens. Subjects will be on study for 28 days from the entry visit through the vaginal ring removal, with a follow-up phone call at day 56 for subjects who accept the additional NuvaRing.

The primary objective is:

• To estimate the effect of ongoing ART containing either once daily ATV/r or EFV, in addition to two or more nucleosides/nucleotides, on the pharmacokinetic (PK) exposure of etonogestrel and ethinyl estradiol in HIV-infected participants at day 21 after placement of the etonogestrel/ethinyl estradiol vaginal ring NuvaRing.

The secondary objectives are:

• To estimate the effect of etonogestrel and ethinyl estradiol on the PK exposure (area under the concentration-time curve [AUC]) of ATV, ritonavir (RTV), or EFV, among HIV-infected participants at day 21 after placement of the etonogestrel/ethinyl estradiol NuvaRing.
• To estimate the effect of ATV/r or EFV-based ART on the PK exposure of etonogestrel and ethinyl estradiol in HIV-infected participants on days 7 and 14 after placement of the NuvaRing.
• To estimate the effect of etonogestrel and ethinyl estradiol on other PK parameters of ATV, RTV, and EFV, such as minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), , and apparent clearance (CL/F).
• To evaluate the safety and toxicity of concomitant ART administered with the vaginal ring, as measured by the short-term impact of the combination hormone therapy administered through a vaginal ring on plasma HIV-1 virologic suppression at day 21, the occurrence of breakthrough bleeding, local genital (grade ≥2) and systemic toxicities related to hormone exposure, or other hormone-related toxicities.
• To determine whether etonogestrel/ethinyl estradiol delivered via a vaginal ring suppresses ovulation in each study group, as measured by the proportion of participants whose progesterone level is >5 ng/mL at days 7, 14, 21, and 28.
Primary endpoint:

• Etonogestrel and ethinyl estradiol concentrations obtained at study day 21 (before the vaginal ring is removed) from participants enrolled in all the three study arms.


Secondary endpoints:

• Evaluation of effect of EFV or ATV-based ART on etonogestrel and ethinyl estradiol PKs:
o Etonogestrel and ethinyl estradiol concentrations obtained on study days 7 and 14 after vaginal ring administration in all three study arms.

• Evaluation of effect of etonogestrel and ethinyl estradiol on EFV PKs:
o EFV PK parameters,
StatusFinished
Effective start/end date12/1/1411/30/17

Funding

  • Brigham and Womens Hospital (110229//5UM1AI068636-10)
  • National Institute of Allergy and Infectious Diseases (110229//5UM1AI068636-10)

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