A Study to Compare Three Different Formulations of Tenofovir 1% Gel When Administered Rectally

Summary

This is a double-blinded, randomized, safety, acceptability, pharmacokinetic, and ex vivo efficacy study of three rectally-applied tenofovir-based microbicide formulations. Approximately 18 total evaluable HIV-negative men and women (\~9 per site) will be enrolled across two study sites: University of California at Los Angeles (UCLA) and Magee-Womens Research Institute (MWRI) at University of Pittsburgh.

Each participant will experience seven rectal exposures to the rectal-specific formulation (RF) and seven rectal exposures to the reduced glycerin vaginal formulation (RGVF) of tenofovir 1% gel, but only one exposure to the vaginal formulation (VF), which will be coupled with six preceding exposures to the Universal HEC Placebo Gel to balance out the VF study stage. Participant accrual will take approximately 6 months and each participant will be on study for approximately 3 months. The total duration of the study will be approximately 1 year.

The primary objectives of the study are safety, acceptability, and pharmacokinetics, specifically:

* To evaluate the safety of each tenofovir-based microbicide gel formulation when applied rectally
* To evaluate the acceptability of each tenofovir-based microbicide gel formulation when applied rectally
* To compare systemic and compartment pharmacokinetics among the three tenofovir-based microbicide gel formulations when applied rectally

Secondary objective of the study is to evaluate the mucosal immunotoxicity of each tenofovir-based microbicide gel formulation when applied rectally.

And the exploratory objective of the study is to assess the preliminary (ex vivo) efficacy of each tenofovir-based microbicide gel formulation using biopsy explants after each product is applied rectally.

Conditions

• HIV Prevention

Interventions

DRUG

Rectal formulation (RF) of tenofovir 1% gel

The RF is a translucent colorless viscous gel formulation containing 1% (w/w) of tenofovir (PMPA) formulated in purified water with EDTA, glycerin, methylparaben, propylparaben, carbopol, sodium carboxy methyl cellulose, and pH adjusted to 7. The RF is close to isoosmolar with an osmolality of 479 mOsmol/kg. Seven doses of this formulation will be used.

DRUG

Vaginal formulations (original VF and reduced vaginal glycerin formulation RGVF) of tenofovir 1% gel

The original VF is a transparent, viscous gel formulation containing 1% (weight/weight) of tenofovir (PMPA, 9-\[(R)-2-(phosphonomethoxy) propyl\]adenine monohydrate), formulated in purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben, hydroxyethylcellulose, and pH adjusted to 4-5. One dose of this formulation will be used, with 6 doses of the HEC placebo gel preceding it to balance out this study stage. The reduced glycerin formulation (RGVF) is a modification of the original VF - it has lower glycerin content than the VF and a significantly reduced osmolality (836 or 846 versus 3111 mOsmol/kg). Lowering the glycerin content lowered the viscosity, so the HEC concentration was increased by 10% (a change considered to be insignificant). The amount of parabens was increased by 10% each to improve the antimicrobial effectiveness. The RGVF formulation has since been modified to increase the viscosity. Seven doses of RGVF will be used in this study.

DRUG

Universal HEC Placebo Gel Formulation

The Universal HEC Placebo Gel contains hydroxyethylcellulose as the gelling agent, purified water, sodium chloride, sorbic acid and sodium hydroxide. The gel is isotonic and formulated at a pH of 4.4 to avoid disrupting the normal vaginal pH and has minimal buffering capacity to avoid the inactivation of sexually transmitted pathogens. Hydroxyethylcellulose is used to approximate the viscosity of microbicide gel candidates. Each pre-filled applicator will deliver approximately 4 mL of HEC placebo gel. Six doses of this gel will be used to balance out the VF stage of the study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• CONRAD

  collaborator OTHER

• Ian McGowan

  lead OTHER

Principal Investigators

• Ian McGowan, MD, PhD, FRCP · Magee-Women's Research Institute

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-03-31

Primary Completion

2013-11-30

Completion

2013-11-30

Countries

• United States

Study Locations