Evaluating Pharmacokinetic Interactions With Vaginal Ring Contraceptives and ART
Information source: AIDS Clinical Trials Group
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV-1 Infection
Intervention: Etonogestrel/ethinyl estradiol vaginal ring (NuvaRing) (Device); Efavirenz (Drug); Atazanavir/Ritonavir (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: AIDS Clinical Trials Group
Summary
This study will look at a method of hormonal birth control, called the NuvaRing, and
specific anti-HIV medications, called antiretrovirals (ARVs). Some studies of women who use
a hormonal birth control method (specifically oral pills, patches, and injections) and take
ARVs have shown that ARVs interact with the hormones released by the birth control
medication. These interactions may cause the birth control to be less effective at
preventing pregnancy. There is also concern that hormonal birth control can increase HIV
spreading to others, but more studies are needed to determine if this is true. The
investigators do not know whether the NuvaRing and ARVs interact when they are used
together, so this study will look to see if certain ARVs (efavirenz and
atazanavir/ritonavir) interact with the two hormones released by NuvaRing. This will help us
to determine if NuvaRing is safe and effective for women with HIV infection who are taking
ARVs. The study will also include HIV-infected women who are not on ARVs but will use the
NuvaRing to show us what the hormone levels are like in a similar group of women not on
ARVs.
Vaginal rings are also currently being studied to deliver anti-HIV medications that may
prevent HIV acquisition, and to provide birth control over a longer period of time (more
than 1 month). Since vaginal rings will become more commonly used to administer medications,
the investigators want to better understand the potential for drug interactions with drugs
given vaginally. This study will also help us understand the potential for drug interactions
between ARVs given orally, and other drugs given through vaginal rings, like the NuvaRing.
Additionally, this study will help us understand how hormones released from a vaginal ring
affect the amount of HIV virus in the genital tract, the bacterial make-up (microbiome) of
the female genital track, and the immune system within the genital tract, all of which may
affect the chances of spreading HIV.
Clinical Details
Official title: Evaluating Pharmacokinetic Interactions With Vaginal Ring Contraceptives and Antiretroviral Therapy (ART)
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Etonogestrel and ethinyl estradiol concentrations at study day 21
Secondary outcome: Etonogestrel and ethinyl estradiol concentrations obtained on study days 7 and 14 after vaginal ring administration in all three study armsEfavirenz (EFV) Pharmacokinetics (PK) area under curve (AUC)(0-24h), Cmin, Cmax, Tmax, and CL/F calculated based on intensive EFV PK samples obtained from individual participants enrolled in Arm B ATV and RTV PK AUC(0-24h), Cmin, Cmax, Tmax, and CL/F calculated based on intensive ATV and RTV PK samples obtained from individual participants enrolled in Arm C. HIV-1 RNA copies obtained from individual participants enrolled in all of the three study Arms A, B, and C Any signs and symptoms of grade 2 or higher related to vaginal ring exposure from individual participants enrolled in all of the three study Arms A, B, and C Hormone progesterone levels obtained from individual participants enrolled in all of the three study Arms A, B, and C
Eligibility
Minimum age: 16 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Documented HIV-1 infection.
- Participants must be receiving either 1) EFV 600 mg daily with 2 or more NRTIs, 2)
ATV/r 300 mg/ 100 mg daily with TDF 300 mg and 1 or more additional NRTIs, or 3) no
ART. ART regimens should be stable for 30 days prior to study entry with no plans to
change therapy during the first 28 days of this study. Participants receiving no ART
should have no plans to initiate ART during the first 28 days of the study.
NOTE: Participants must have access to their ART regimens through their primary care
providers. ART medications are not supplied by this study.
- For participants on ART, documentation of plasma HIV-1 RNA = 400 copies/mL obtained
within 60 days prior to study entry.
- For participants not on ART, CD4+ cell count must be ≥350 cells/mm3, obtained within
60 days prior to study entry.
- Laboratory values within 60 days prior to study entry:
- Platelet count ≥50,000 platelets/mm3
- Hemoglobin ≥8. 0 g/dL
- Aspartate transaminase (SGOT) and alanine aminotransferase (SGPT) <5 x upper
limit of normal (ULN)
- Creatinine ≤1. 5 x ULN
- Total bilirubin ≤2. 0 x ULN
- Last menstrual period =6 months prior to study entry. If last menstrual period >6
months prior to study entry without another cause for amenorrhea, such as recent
pregnancy, serum follicle-stimulating hormone (FSH) must be checked and be = 40
mIU/mL to be eligible for enrollment.
- Premenopausal females with at least one functioning ovary.
- Documentation of Pap smear within 1 year prior to study entry.
- Negative serum or urine-HCG pregnancy test with a sensitivity of ≤25 mIU/mL within 60
days prior to study entry and within 24 hours prior to study entry
- All participants must agree not to participate in a conception process (eg, active
attempt to become pregnant or in vitro fertilization) for the duration of the study.
Because it is unknown if ARVs will adversely affect the efficacy of NuvaRing as a
contraceptive method, participants of reproductive potential, who are participating
in sexual activities that could lead to pregnancy, must agree to use an additional
reliable form of contraception while in the study. Acceptable additional methods of
contraception include:
- Condoms (male or female) with or without a spermicidal agent
- Non-hormonal intrauterine device (IUD)
Other hormonal forms of contraception are not allowed during the study period.
Condoms should be used to prevent transmission of HIV and sexually transmitted diseases
between sexual partners.
NOTE: Participants with bilateral tubal ligation or non-hormonal IUD may be enrolled.
Exclusion Criteria:
- Received depot medroxyprogesterone acetate (DMPA) within 4 months prior to study
entry.
- Received other hormonal therapies (eg, oral contraceptive agents, hormone- containing
vaginal ring, contraceptive patch, hormone replacement therapy, anabolic therapies,
including nandrolone decanoate or megestrol acetate) within 30 days prior to study
entry.
- Breastfeeding.
- Less than 6 weeks postpartum at study entry.
- Use of any prohibited medications within 30 days prior to study entry.
- Initiated, discontinued, or changed doses of drugs that are CYP substrates or known
to have drug interactions with ethinyl estradiol or etonogestrel within 30 days prior
to study entry.
- Bilateral oophorectomy.
- For women older than 35 years of age, smoking 15 or more cigarettes per day.
- History of invasive cancer of the reproductive tract; known or suspected malignancy
of the breast, or known increased risk for breast cancer; undiagnosed abnormal
vaginal bleeding; liver tumors; or serious ocular disorders at any time prior to
study entry.
- Chronic immunosuppressive conditions other than HIV.
- Use of systemic or inhaled corticosteroids such as for acute therapy for Pneumocystis
pneumonia (PCP) or asthma exacerbation and prednisone ≥10 mg (or equivalent) for any
reason other than a stable or tapering dose.
- History of deep venous thrombosis or pulmonary embolism.
- History of cerebral vascular or coronary artery disease.
- Severe uncontrolled hypertension within 60 days prior to study entry.
- Diabetes with vascular involvement.
- Clinically active cervical or vaginal infection at study entry. NOTE: Gonorrhea,
chlamydia, and trichomonas testing will be performed during screening using
techniques available at the local sites and documented in source documentation and
case report forms (CRFs). Testing for bacterial vaginosis, performed using techniques
available at the local sites, is only necessary if the participant is symptomatic and
the provider feels treatment may be necessary. Women with genital herpes lesions
should wait to be screened until the herpetic lesions have healed.
- Acute infections or other opportunistic diseases requiring medication within 14 days
prior to study entry.
Locations and Contacts
Gaborone Prevention/Treatment Trials CRS (12701), Gaborone, Botswana; Recruiting Tebogo Kakhu, Phone: (011 267) 393-1146, Email: tkakhu@bhp.org.bw Anthony Ogwu, MBBS, Principal Investigator
Instituto de Pesquisa Clinica Evandro Chagas (12101), Rio de Janeiro 21045, Brazil; Recruiting Sandra W. Cardoso, Phone: 552-125-644933, Email: sandra.wagner@bol.com.br Beatriz Grinsztejn, MD, PhD, Principal Investigator
Asociacion Civil Impacta Salud y Educacion - Miraf CRS (11301), Lima 18 PE, Peru; Recruiting Juan V. Guanira, MD, MPH, Phone: 51-124-23072, Email: jguanira@impactaperu.org Jorge Sanchez, MD, MPH, Principal Investigator
Puerto Rico-AIDS CRS (5401), San Juan 00935, Puerto Rico; Recruiting Sylvia I. Davila Nieves, M.S., Phone: 787-767-9192, Email: sylvia.davila@upr.edu Jorge L Santana-Bagur, MD, Principal Investigator
San Juan Hospital PR NICHD CRS (5031), San Juan 00936, Puerto Rico; Recruiting Lizbeth Fabregas-Troche, MS, Email: lfabregas@SanJuanCapital.com Midnela Acevedo-Flores, MT, MD, Principal Investigator
UZ-Parirenyatwa CRS (30313), Harare, Zimbabwe; Recruiting Jimijika Batani, B.A., Phone: 263-912272818, Email: jbatani@uz-ucsf.co.zw James Hakim, MD, MSc, FRCP, Principal Investigator
31788 Alabama CRS, Birmingham, Alabama 35294, United States; Recruiting Karen G Savage, BSN, Phone: 205-996-2373 Edgar Overton, MD, Principal Investigator
University of Southern California (1201), Los Angeles, California 90033-1079, United States; Recruiting Luis M Mendez, Phone: 323-343-8283, Email: lmendez@usc.edu Fred Sattler, MD, Principal Investigator
University of Florida Jacksonville (5051), Jacksonville, Florida 32209, United States; Recruiting Kathleen Thoma, MA, Phone: 904-244-5331, Email: kathleen.thoma@jax.ufl.edu Mobeen H Rathore, MD, Principal Investigator
Univ. of Miami AIDS CRS (901), Miami, Florida 33136, United States; Recruiting Leslie Thompson, RN, BSN, Phone: 305-243-3838, Email: lthomps@gate.net Margaret A. Fischl, MD, Principal Investigator
Northwestern University CRS (2701), Chicago, Illinois 60611, United States; Recruiting Baiba Berzins, MPH, Phone: 312-695-5012, Email: baiba@northwestern.edu Babafemi Taiwo, MBBS, MD, Principal Investigator
Rush University Cook County Hospital Chicago NICHD CRS (5083), Chicago, Illinois 60612, United States; Recruiting Maureen Haak, RN, MSN, Phone: 312-572-4541, Email: maureen_haak@rush.edu James B McAuley, MD, MPH, Principal Investigator
Investigaciones Medicas en Salud (INMENSA) (11302), San Isidro, Lima, Peru; Recruiting Fanny Garcia, R.N., Phone: 011-51-1-5621600, Ext: 103, Email: fgarcia@impactaperu.org Aldo Lucchetti, M.D., Principal Investigator
Johns Hopkins Adult AIDS CRS (201), Baltimore, Maryland 21287, United States; Recruiting Ilene Wiggins, RN, Phone: 410-614-2766, Email: imp@jhmi.edu Charles Flexner, MD, Principal Investigator
31786 New Jersey Medical School Clinical Research Center CRS, Newark, New Jersey 07103, United States; Recruiting Janet Forcht, Phone: 973-972-1005, Email: janet.forcht@rutgers.edu Shobha Swaminathan, MD, Principal Investigator
New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477), Newark, New Jersey 07103, United States; Recruiting Nancy Reilly, RN, MS, ACRN, Phone: 973-972-1268, Email: reillyna@umdnj.edu Sally Hodder, MD, Principal Investigator
31787 University of Rochester Adult HIV Therapeutic Strategies Network CRS, Rochester, New York 14642, United States; Recruiting Emily L. Cosimano, RN, Phone: 585-276-5903 Amneris Luque, MD, Principal Investigator
AIDS Community Health Ctr. ACTG CRS (1108), Rochester, New York 14604, United States; Recruiting Carol Greisberger, RN, CCRC, Phone: 585-275-2740, Email: Carol_Greisberger@urmc.rochester.edu Roberto Corales, DO, Principal Investigator
Univ. of Rochester ACTG CRS (1101), Rochester, New York 14642, United States; Recruiting Carol Greisberger, RN, BS, Phone: 585-275-2740, Email: carol_greisberger@urmc.rochester.edu Amneris Luque, MD, Principal Investigator
Unc Aids Crs (3201), Chapel Hill, North Carolina 27514, United States; Recruiting Cheryl J. Marcus, BSN, RN, Phone: 919-843-8761, Email: cjm@med.unc.edu David A. Wohl, MD, Principal Investigator
Metro Health CRS (2503), Cleveland, Ohio 44109, United States; Recruiting Julie Ziegler, Phone: 216-778-7847, Email: jziegler@metrohealth.org Robert C. Kalayjian, MD, Principal Investigator
The Miriam Hosp. ACTG CRS (2951), Providence, Rhode Island 02906, United States; Recruiting Pamela Poethke, RN, Phone: 401-793-4971, Email: ppoethke@lifespan.org Karen T. Tashim, MD, Principal Investigator
Additional Information
Starting date: November 2014
Last updated: August 5, 2015
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