A Feasibility Study to Assess Tenofovir and Maraviroc Protection Against HIV-1 in Cervical and Vaginal Explants

NCT02039323 | Completed Phase 1

• 1 other identifier: 13-3940
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the feasibility of a novel method to assess antiretroviral efficacy for protection against HIV-1 infection in vaginal and cervical tissue biopsies.

Conditions

Healthy Adult Females

Keywords

Tenofovir; Tenofovir disoproxil; Maraviroc; Pharmacologic Actions; Anti-HIV agents; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• Evidence of explant infection

  To determine if oral administration of tenofovir plus maraviroc can protect mucosal tissues from HIV infection in an ex-vivo HIV challenge of biopsies collected post-dose.

  2 days post-biopsy

Study Arms (1)

All Participants

EXPERIMENTAL

Maraviroc 600 mg + Tenofovir 600 mg

Drug: Tenofovir; Drug: Maraviroc

Interventions

Tenofovir DRUG

Also known as: Tenofovir disoproxil fumurate, Viread

All Participants

Maraviroc DRUG

Also known as: Selzentry

All Participants

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 18-49, inclusive, with an intact 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 (eCcr) of at least 80 mL/min by the Cockcroft-Gault formula where: eCcr (female) in mL/min = \[(140 - age in years) x (weight in kg) x 0.85\] / (72x serum creatinine in mg/dL).
• All subjects must have a negative serum pregnancy test at screening and negative urine pregnancy tests on days of dose administration and should be using at least one of the following methods of contraception from the screening visit through 72 hours prior to first outpatient visit (at which time the women will be asked to remain abstinent until after their follow-up visit)
• Systemic hormonal contraceptive (oral, depot, transdermal or implant)
• Intrauterine device placed at least 1 month prior to study enrollment
• Bilateral tubal ligation (Sterilization)
• Vasectomized male partners
• 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
• Body Mass Index (BMI) of approximately 18 to 34 kg/m2; and a total body weight \> 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.
• Subject must have documentation of 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. If subjects have had a gynecological exam but no history of Pap smear, a Pap smear will be completed at screening and paid for by the study.
• Subject must be willing to abstain from sexual intercourse, douching, and all intravaginal objects and products for at least 72 hours prior to first study visit until study completion.
• Subject must be HIV-1 and Hepatitis B surface antigen negative as documented on screening labs.

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, or other clinically significant surgery of the female genital tract.
• 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 medication dosing.
• 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 (HCV) infection as defined by positive HCV Ab (determined by multi-antigen EIA) and detectable Hepatitis C RNA.
• A positive test for syphilis, gonorrhea, Chlamydia, or trichomonas at screening.
• Any laboratory chemistry or hematology result Grade 2 or greater according to the Division of Allergy and Infectious Disease (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.
• Use of prescription or nonprescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of trial medication and unable to avoid use during the inpatient pharmacokinetic visit. As an exception, systemic hormonal methods of contraception can be continued.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

CTRC University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Interventions

Tenofovir; Maraviroc

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Angela DM Kashuba, PharmD

  UNC at Chapel hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PharmD

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 17, 2014
• Study Start: February 1, 2014
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: June 19, 2014

Record last verified: 2014-06

Locations

US (1)