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

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.

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.

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.