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The purpose of this study is to develop a predictive antiretroviral pharmacokinetic model of mucosal fluid and tissue distribution in genital tract fluid, rectal fluid and 3 mucosal tissues. This will be accomplished by determining the pharmacokinetic disposition and dose proportionality of four antiretrovirals (tenofovir, emtricitabine, maraviroc, and raltegravir) in human rectal and cervicovaginal fluid and rectal, cervical, and vaginal tissue.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TDF 150mg + MVC 150mg | Experimental | Subjects will receive a single dose of tenofovir 150 mg and maraviroc 150 mg. |
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| TDF 300mg + MVC 300mg | Experimental | Subjects will receive a single dose of tenofovir 300 mg and maraviroc 300 mg. |
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| TDF 600mg +MVC 600mg | Experimental | Subjects will receive a single dose of tenofovir 600 mg and maraviroc 600 mg. |
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| FTC 100mg + RAL 200mg | Experimental | Subjects will receive a single dose of emtricitabine 100 mg and raltegravir 200 mg. |
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| FTC 200mg + RAL 400mg | Experimental | Subjects will receive a single dose of emtricitabine 200 mg and raltegravir 400 mg. |
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| FTC 400mg + RAL 800mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pharmacokinetic Sampling | Other | Blood plasma, Rectal, Cervical, and Vaginal Tissues and Secretions |
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| Measure | Description | Time Frame |
|---|---|---|
| Dose Proportionality | To determine if antiretroviral mucosal fluid and tissue concentrations change proportionally with a change in antiretroviral dose. | 48 hours |
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Inclusion Criteria:
Healthy pre-menopausal female subjects between the ages of 18 and 49 years, inclusive, with an intact gastrointestinal tract, uterus, and cervix. (Healthy is defined as no irregular menstrual cycles or 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.)
All subjects must have an estimated calculated creatinine clearance of at least 80 mL/min by the Cockcroft-Gault formula
All subjects must have a negative serum pregnancy test at screening and negative urine pregnancy tests on days of sampling and should be using at least one of the following methods of contraception:
Systemic hormonal contraceptive (oral, depot, transdermal or implant)
IUD placed at least 1 month prior to study enrollment
Bilateral tubal ligation (Sterilization)
Vasectomized male partner
Condom + Spermicide
*Unless engaged in sexual activity with female only sex partners or abstinent for at least 3 months prior with no intention of becoming sexually active during the study period. Any history of recent or present concomitant male sex partners will be addressed and ruled out in the context of screening participants for eligibility for the protocol
Female only partner
Body Mass Index (BMI) of approximately 18 to 34 kg/m^2; and a total body weight > 45 kg (99 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.
Subject must have a normal pap smear within 36 months of the screening visit, no procedures for abnormal cervical/vaginal pathology in the last six months, at least one prior gynecological visit as part of subject's routine medical history.
Subject must be willing to abstain from sexual intercourse, douching, and all intravaginal and intrarectal products at least 72 hours prior to Day 1 until study completion.
Subject must be HIV-1 and Hepatitis B surface antigen negative as documented on screening labs.
Subject must not be actively involved in the conception process.
Subject must be able to swallow pills and have no allergies to any component of the study products.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Angela DM Kashuba, PharmD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UNC Hospitals CTRC | Chapel Hill | North Carolina | 27514 | United States |
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Subjects will receive a single dose of emtricitabine 400 mg and raltegravir 800 mg. |
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