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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 arms

Efavirenz (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 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 without another cause for amenorrhea, such as recent pregnancy, serum follicle-stimulating hormone (FSH) must be checked and be - 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

Page last updated: August 23, 2015

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