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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: Raltegravir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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). Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Raltegravir<br>To test raltegravir to see if it can be detected in gastrointestinal tissue of healthy men. | Drug: Raltegravir<br>* 400 mg tablets by mouth BID from Day 1 - Day 7 after enrollment visit<br>* Other names: ISENTRESS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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raltegravir, pharmacokinetics, healthy, male, volunteers, gastrointestinal, tract