Clinical trial NCT01325051: Study to Characterize the Pharmacokinetics of Raltegravir in the Gastrointestinal (GI) Tract of Healthy Male Volunteers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: raltegravir
pharmacokinetics
healthy
male
volunteers
gastrointestinal
tract
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-03-29
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

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 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

Primary outcomes:
measure: AUC = Area under the concentration versus time curve of raltegravir
timeFrame: 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 outcomes:
measure: Cmax = maximum concentration of raltegravir
timeFrame: 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)
measure: Tmax = time to maximum concentration of raltegravir
timeFrame: 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)
measure: C12 = concentration at 12 hours after dose of raltegravir
timeFrame: 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)
measure: t1/2 = half-life of raltegravir
timeFrame: 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)
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC-CH School of Pharmacy
name: Angela Kashuba, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: UNC-CH Division of Infectious Diseases
name: Kristine Patterson, MD
role: PRINCIPAL_INVESTIGATOR
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