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Study to Characterize the Pharmacokinetics of Raltegravir in the Gastrointestinal (GI) Tract of Healthy Male Volunteers

Information source: University of North Carolina, Chapel Hill
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Healthy Volunteer

Intervention: Raltegravir (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Angela Kashuba, PharmD

Official(s) and/or principal investigator(s):
Angela Kashuba, PharmD, Principal Investigator, Affiliation: UNC-CH School of Pharmacy
Kristine Patterson, MD, Principal Investigator, Affiliation: UNC-CH Division of Infectious Diseases

Summary

The purpose of this study is to characterize the way the first commercially available integrase inhibitor, raltegravir, a new class of antiretrovirals that is used to treat HIV, is distributed into the rectal mucosal tissue. This information will generate important information regarding the drug's penetration into lymphoid tissues that are rapidly depleted in HIV infection. Subsequently strategies to prevent the sexual transmission of HIV and for treating HIV-infected individuals will be designed.

Clinical Details

Official title: A Phase IV, Open-Label Study to Characterize the First-Dose and Multiple-Dose Pharmacokinetics of Raltegravir in the Gastrointestinal Tract of Healthy Male Volunteers

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Primary outcome: AUC = Area under the concentration versus time curve of raltegravir

Secondary outcome:

Cmax = maximum concentration of raltegravir

Tmax = time to maximum concentration of raltegravir

C12 = concentration at 12 hours after dose of raltegravir

t1/2 = half-life of raltegravir

Detailed description: Participants: 14 HIV-uninfected, healthy, male volunteers, ≥18 and ≤49 years of age, will be recruited and enrolled. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG, and clinical laboratory tests. Participants of all races and ethnicities will be considered for enrollment. This study will be conducted at a single site in the United States: the University of North Carolina at Chapel Hill. Procedures (methods): An outpatient screening visit will be conducted on all potential participants to obtain informed consent and evaluate for eligibility. Once enrolled, all subjects will take 400 mg oral dose of raltegravir twice daily from Day 1 to Day 7. The healthy men enrolled in this study will undergo single-dose and multiple-dose pharmacokinetic sampling. Blood will be collected via peripheral IV at pre-dose, and at 1, 2, 3, 4, 6, 8 and 12 hours post-dose. Subjects will undergo two colonoscopies during sampling visits (Day 1 and Day 7) for the purpose of obtaining gastrointestinal-associated lymphoid tissue (GALT). Each subject will have his biopsy obtained at one of the following time points post-dose: 1, 2, 3, 4, 6, 8, and 12 hours. Seven to ten days after their last inpatient sampling visit, all subjects will complete a follow-up visit.

Eligibility

Minimum age: 18 Years. Maximum age: 49 Years. Gender(s): Male.

Criteria:

Inclusion Criteria: 1. Healthy male subjects between the ages of 18 and 49 years, inclusive, with intact genital tract and gastrointestinal tract. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG, and clinical laboratory tests. 2. Body Mass Index (BMI) of approximately 18 to 30 kg/m^2; and a total body weight greater than or equal to 50 kg (110 lbs). 3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial. 4. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Exclusion Criteria 1) any medical condition or finding deemed by the investigators to be ineligible

Locations and Contacts

University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
Additional Information

Related 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.

Barau C, Delaugerre C, Braun J, de Castro N, Furlan V, Charreau I, Gérard L, Lascoux-Combe C, Molina JM, Taburet AM. High concentration of raltegravir in semen of HIV-infected men: results from a substudy of the EASIER-ANRS 138 trial. Antimicrob Agents Chemother. 2010 Feb;54(2):937-9. doi: 10.1128/AAC.01261-09. Epub 2009 Dec 7.

Starting date: April 2011
Last updated: January 3, 2012

Page last updated: August 23, 2015

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