NCT01575418

An Exploratory Rectal Safety Study of Three Tenofovir Gel Formulations

An Exploratory, Double-Blinded, Randomized, Pharmacokinetic and Safety Study of Three Rectally-Applied Tenofovir 1% Microbicide Gel Formulations

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Ian McGowan · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This is a double-blinded, randomized, pharmacokinetic and safety study of 3 rectally applied tenofovir microbicide formulations: a vaginal formulation (VF), a reduced glycerin vaginal formulation (RGVF), and a rectal-specific formulation (RF). Nine HIV-negative men will be enrolled. Each participant will receive two inpatient doses of each radiolabeled study product. The first inpatient dose of each product will be administered without coital dynamics simulation (CDS), while the second inpatient dose will be followed by a CDS procedure at 1-hour post dose with instillation of radiolabeled autologous semen. There will be a washout period of at least 11 days between each dose.

Conditions

• HIV Prevention

Interventions

Type	Name	Description
DRUG	Rectal formulation (RF) of tenofovir 1% gel	The RF is 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.
DRUG	Vaginal formulation (VF) of tenofovir 1% gel	The original VF is a transparent, viscous gel formulation containing 1% (weight/ weight or w/w) 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. This formulation has been used in all clinical trials (vaginal, penile, and rectal) of tenofovir 1% gel to date.
DRUG	Reduced glycerin vaginal formulation (RGVF) of tenofovir 1% gel	Modified slightly from the original VF formulation, the RGVF has a lower glycerin content than the VF and a significantly reduced osmolality (836 or 846 versus 3111 mOsmol/kg). Lowering 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 antimicrobical effectiveness. The RGVF formulation with 2.75% HEC was used in MTN-007 (CONRAD IND 73,382; currently enrolling), which is the only clinical study of this formulation. The RGVF formulation has since been modified to increase the viscosity.
RADIATION	Radiolabeling of study drugs and semen	Study products (i.e. the gel formulations) will be radiolabeled with 111In-DTPA, an FDA-approved radiopharmaceutical commonly used in diagnostic nuclear medicine studies. The delivered dose per gel study product will be approximately 100 microCuries (µCi) to allow sufficient visualization for the imaging period. Autologous whole semen collected from the participants at designated visits will be radiolabeled with a delivered dose of approximately 500 microCuries (µCi) of 99mTc-sulfur colloid, also an FDA-approved radiopharmaceutical commonly used in diagnostic nuclear studies. The study team at JHU has extensive experience administering these radiopharmaceuticals rectally. Both of these radiopharmaceuticals will be prepared and delivered by a commercial radiopharmacy and mixed by the study investigators with the respective gel and whole semen vehicles. The study product and autologous whole semen will be loaded into calibrated syringes with luer lock adapter for dosing.

Timeline

• Start date: 2013-03-01
• Primary completion: 2013-11-01
• Completion: 2013-11-01
• First posted: 2012-04-11
• Last updated: 2014-05-08

Locations

1 site across 1 country: United States