A Pilot Study to Characterize the Pharmacokinetics of Raltegravir in the Cervicovaginal Fluids of HIV-infected Women - Full Text View

Sponsor:	The University of North Carolina, Chapel Hill
Collaborator:	Merck
Information provided by:	The University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:	NCT00774683

Purpose

The purpose of this research sub-study is to learn about the levels of an antiretroviral (ARV) medication called Raltegravir, and response to HIV virus in the genital tract of HIV-positive women.

We would like to see how this study medication is tolerated, and how the body processes the study medication in women who are HIV-positive. More specifically, we are interested in how Isentress® might penetrate into the female cervicovaginal secretions thereby potentially reducing the amount of HIV in those secretions. A reduction in the amount of HIV in genital secretions may prevent female subjects from transmitting HIV to their sexual partners. This information will help the research team know how a medication such as Isentress® might be used to prevent the sexual transmission of HIV.

Condition	Intervention
HIV AIDS	Drug: Raltegravir (Isentress®)

Study Type:	Observational
Study Design:	Cohort, Prospective
Official Title:	A Phase IV, Open-Label, Single-Sequence Pilot Study to Characterize the Pharmacokinetics of a 400mg Oral Dose of Raltegravir in the Cervicovaginal Fluids of HIV-Infected Women

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Raltegravir

U.S. FDA Resources

Further study details as provided by The University of North Carolina, Chapel Hill:

Primary Outcome Measures:

To characterize the pharmacokinetics of raltegravir in cervicovaginal fluids of HIV-infected women, and compare this to the blood plasma pharmacokinetics being obtained in the main study, CID 0706. [ Time Frame: Single Time Point Measurement at 4 Weeks after ART Initiation ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

blood specimens and cervicovaginal fluids

Estimated Enrollment:	6
Study Start Date:	August 2008
Estimated Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Sub-study Group A Six HIV-positive African American women from the main study, CID 0706	Drug: Raltegravir (Isentress®) 400 mg p.o. BID x 7 days

Detailed Description:

Purpose: This study aims to characterize the pharmacokinetics of raltegravir in cervicovaginal fluids of HIV-infected women, and compare this to the blood plasma pharmacokinetics being obtained in the main study, CID 0706.

Participants: Six HIV-positive women from the CID 0706 study Procedures: During the pharmacokinetic visit to obtain blood plasma in the CID 0706 study, women will be asked to self-collect cervicovaginal samples using a vaginal aspirator at the following timepoints: pre-dose and 1, 2, 4, 6, 8, and 12 hours after raltegravir 400mg dose administration.

Eligibility

Ages Eligible for Study:	18 Years to 49 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

UNC ID Clinic, Durham County Health Department, Wake County Health Department

Criteria

Inclusion Criteria:

HIV-1 infection documented by HIV serology or detectable viral load
Self-described as African-American
Less than 7 days cumulative of prior HIV therapy
Plasma HIV RNA PCR equal to or greater than 1000 copies/mL within 90 days prior to study entry
Able to provide informed consent
In the opinion of the investigator, able to comply with study medication and procedures
ALT (SGPT) < or equal to 3.0 x ULN within 45 days prior to study entry
GRF > 60 as calculated by MDRD within 45 days prior to study entry
All women of reproductive potential (who have not reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation) must have a negative serum or urine β-HCG pregnancy test performed within 48 hours before entry.

All study volunteers must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) and, if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use at least one reliable method of contraception (e.g., condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an IUD; or hormonal-based contraception), simultaneously while receiving the protocol-specified medication(s) and for 6 weeks after stopping the medication(s).

Exclusion Criteria:

Pregnancy
Breastfeeding
Prior receipt of Raltegravir
Any condition which in the opinion of the investigator is likely to interfere with follow-up or ability to take the study medication appropriately
A positive test for bacterial vaginosis, syphilis, gonorrhea, Chlamydia, HSV-2 (active lesions), or trichomonas at entry or week 2 of the main study, CID 0706

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00774683

Locations

United States, North Carolina
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27514

Sponsors and Collaborators

The University of North Carolina, Chapel Hill

Merck

Investigators

Principal Investigator:	Kristine B Patterson, MD	The University of North Carolina, Chapel Hill
Principal Investigator:	Angela DM Kashuba, PharmD	The University of North Carolina, Chapel Hill

More Information

Publications:

Musicco M, Lazzarin A, Nicolosi A, Gasparini M, Costigliola P, Arici C, Saracco A. Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Italian Study Group on HIV Heterosexual Transmission. Arch Intern Med. 1994 Sep 12;154(17):1971-6.

Otten RA, Smith DK, Adams DR, Pullium JK, Jackson E, Kim CN, Jaffe H, Janssen R, Butera S, Folks TM. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J Virol. 2000 Oct;74(20):9771-5.

Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V; Perinatal HIV Prevention Trial (Thailand) Investigators. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med. 2004 Jul 15;351(3):217-28. Epub 2004 Jul 9.

Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557-93. Review.

Pierson T, Hoffman TL, Blankson J, Finzi D, Chadwick K, Margolick JB, Buck C, Siliciano JD, Doms RW, Siliciano RF. Characterization of chemokine receptor utilization of viruses in the latent reservoir for human immunodeficiency virus type 1. J Virol. 2000 Sep;74(17):7824-33.

Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. Erratum in: J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):492.

Cohen MS. Preventing sexual transmission of HIV. Clin Infect Dis. 2007 Dec 15;45 Suppl 4:S287-92.

Responsible Party:	The University of North Carolina at Chapel Hill ( Kristine B. Patterson, MD and Angela DM Kashuba, PharmD )
Study ID Numbers:	CID 0706 Sub-study A
Study First Received:	October 15, 2008
Last Updated:	December 8, 2009
ClinicalTrials.gov Identifier:	NCT00774683 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by The University of North Carolina, Chapel Hill:

Pilot
Pharmacokinetics
Raltegravir

Cervicovaginal
HIV
Women

ClinicalTrials.gov processed this record on February 08, 2010