Pharmacokinetics of Tenofovir, Emtricitabine, Maraviroc, and Raltegravir in Cervical, Vaginal, and Rectal Tissues and Secretions

NCT01330199 | Completed Phase 1 DMC

• 1 other identifier: 10-1393
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Adult Females

Keywords

Healthy; Female; Volunteer

Outcome Measures

Primary Outcomes (1)

• Dose Proportionality

  To determine if antiretroviral mucosal fluid and tissue concentrations change proportionally with a change in antiretroviral dose.

  48 hours

Study Arms (6)

TDF 150mg + MVC 150mg

EXPERIMENTAL

Subjects will receive a single dose of tenofovir 150 mg and maraviroc 150 mg.

Other: Pharmacokinetic Sampling

TDF 300mg + MVC 300mg

EXPERIMENTAL

Subjects will receive a single dose of tenofovir 300 mg and maraviroc 300 mg.

Other: Pharmacokinetic Sampling

TDF 600mg +MVC 600mg

EXPERIMENTAL

Subjects will receive a single dose of tenofovir 600 mg and maraviroc 600 mg.

Other: Pharmacokinetic Sampling

FTC 100mg + RAL 200mg

EXPERIMENTAL

Subjects will receive a single dose of emtricitabine 100 mg and raltegravir 200 mg.

Other: Pharmacokinetic Sampling

FTC 200mg + RAL 400mg

EXPERIMENTAL

Subjects will receive a single dose of emtricitabine 200 mg and raltegravir 400 mg.

Other: Pharmacokinetic Sampling

FTC 400mg + RAL 800mg

EXPERIMENTAL

Subjects will receive a single dose of emtricitabine 400 mg and raltegravir 800 mg.

Other: Pharmacokinetic Sampling

Interventions

Pharmacokinetic Sampling OTHER

Blood plasma, Rectal, Cervical, and Vaginal Tissues and Secretions

FTC 100mg + RAL 200mg; FTC 200mg + RAL 400mg; FTC 400mg + RAL 800mg; TDF 150mg + MVC 150mg; TDF 300mg + MVC 300mg; TDF 600mg +MVC 600mg

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• Subjects with a history of hysterectomy
• Subjects who are pregnant, possibly pregnant, or lactating
• Subjects with a presence of vaginal discharge or genital bleeding at screening
• History of febrile illness within five days prior to first dose.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug screen.
• A positive result for HIV.
• Active Hepatitis B infection as determined by positive Hepatitis B surface antigen (HbsAg) or Hepatitis B core antibody (HBcAb) tests (in the absence of HBsAb).
• Active Hepatitis C infection as defined by anti-hepatitis C virus serology (determined by multi-antigen EIA) and detectable Hepatitis C viral RNA.
• A positive test for syphilis, gonorrhea, Chlamydia, or trichomonas at screening or symptomatic bacterial vaginosis.
• Any laboratory chemistry or hematology result Grade 2 or greater according to the DAIDS Laboratory Grading Tables.
• Treatment with an investigational drug within 4 months preceding the first dose of trial medication.
• History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week.
• Participation in a clinical trial involving vaginal or rectal biopsies within 12 months preceding the first dose of trial medication.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

UNC Hospitals CTRC

Chapel Hill, North Carolina, 27514, United States

Location

Study Officials

• Angela DM Kashuba, PharmD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: April 6, 2011
• Study Start: February 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: September 17, 2013

Record last verified: 2013-09

Locations

US (1)