Comparison of Tenofovir Vaginal Gel and Film Formulations — FAME-05  

Healthy Clinical Trial

Official title: Comparison of the Pharmacokinetics and Pharmacodynamics of Single Dose Tenofovir Vaginal Gel and Film Formulation

Status Completed

Clinical Trial Summary

This is an open label comparative study of tenofovir gel and film in 10 healthy sexually active women without active female genital tract disorders. The women will receive a single dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and tenofovir film (1.3%;40 mg) - in a crossover study design to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid (primary objective).

Clinical Trial Description

This is an open label comparative study of tenofovir gel and film in 10 healthy sexually active women without active female genital tract disorders. The women will receive a single dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and tenofovir film (1.3%;40 mg) - in a crossover study design to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid (primary objective). Further, pharmacodynamics will be assessed using cervical tissue in an ex vivo HIV biopsy challenge, and safety will be determined by assessment of adverse events following a single dose of each formulation (secondary objective). The primary endpoint will be to determine concentrations of tenofovir (TFV) and its metabolite, tenofovir diphosphate (TFV-DP), in plasma, tissue homogenates, and cervicovaginal fluid. Secondary endpoints will be determined by assessing concentrations of HIV p24 protein from explant aliquot samples up to 21 days post-infection ex vivo, and by determination of Grade 2 or higher adverse events deemed related to study product.

Research participants will receive the first tenofovir dose formulation prior to the following sampling:

• Blood PK plasma collection will be obtained at pre-dose, 0.5, 1, 2, 4, 5, 8 and 12 hours (Day 0), 24 hours (Day 1); 48 hours (Day 2); 72 hours (Day 3); and 168 hours (Day 7) following tenofovir formulation dosing.

• Cervicovaginal fluid sampling, rectal fluid sampling, and cervicovaginal biopsy will be performed (in the sequence listed) 5 and 72 hours after dosing in all subjects. Cervicovaginal fluid and rectal fluid sampling will also be obtained at 168 hours.

Subjects will be counseled to abstain from sexual intercourse and all other insertive vaginal practices for 10 days following each administered dose (or 7 days after the last cervicovaginal sampling at 72 hours). Following a safety evaluation visit, the research participant will return to the research unit and receive a second tenofovir dose formulation followed by the same schedule of sample collection and a final safety visit. PK parameters of TFV and TFV-DP will be estimated and compared between the gel and film formulations. PK parameters will include peak concentration (Cmax), area under the concentration-time curve (AUC), time to peak concentration (Tmax), elimination half-life (t1/2). Tenofovir gel and film ex vivo pharmacodynamics will also be assessed and analyzed for correspondence to pharmacokinetics.

Visit 1 Visits 2-6 Visit 7 Visits 8-12 Visit 13

• 28 Days Day 0-7 Day 14 Day 28-35 Day 42

These studies will be carried out at The Johns Hopkins Hospital under the direction of Craig Hendrix, MD, as the Project PI. ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy
• HIV

• NCT number: NCT02280109
• Study type: Interventional
• Source: CONRAD
• Status: Completed
• Phase: Phase 0
• Start date: November 2014