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

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01325051
• Other study ID #: CID 1020; IRB 10-2321
• Status: Completed
• Phase: Phase 1
• First received: March 23, 2011
• Last updated: January 3, 2012
• Start date: April 2011
• Est. completion date: November 2011

Study information

• Verified date: January 2012
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 49 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• Raltegravir
400 mg tablets by mouth BID from Day 1 - Day 7 after enrollment visit

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Angela Kashuba, PharmD	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC = Area under the concentration versus time curve of raltegravir		0, 1, 2, 3, 4, 6, 8, and 12 hours after single dose (Day 1) and 0, 1, 2, 3, 4, 6, 8, and 12 hours after 13 doses (Day 7)	No
Secondary	Cmax = maximum concentration of raltegravir		0, 1, 2, 3, 4, 6, 8, and 12 hours after single dose (Day 1) and 0, 1, 2, 3, 4, 6, 8, and 12 hours after 13 doses (Day 7)	No
Secondary	Tmax = time to maximum concentration of raltegravir		0, 1, 2, 3, 4, 6, 8, and 12 hours after single dose (Day 1) and 0, 1, 2, 3, 4, 6, 8, and 12 hours after 13 doses (Day 7)	No
Secondary	C12 = concentration at 12 hours after dose of raltegravir		0, 1, 2, 3, 4, 6, 8, and 12 hours after single dose (Day 1) and 0, 1, 2, 3, 4, 6, 8, and 12 hours after 13 doses (Day 7)	No
Secondary	t1/2 = half-life of raltegravir		0, 1, 2, 3, 4, 6, 8, and 12 hours after single dose (Day 1) and 0, 1, 2, 3, 4, 6, 8, and 12 hours after 13 doses (Day 7)	No