An Exploratory Rectal Safety Study of Three Tenofovir Gel Formulations

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

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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• CONRAD

  collaborator OTHER

• Ian McGowan

  lead OTHER

Principal Investigators

• Craig Hendrix, MD · Johns Hopkins University

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-03-31

Primary Completion

2013-11-30

Completion

2013-11-30

Countries

• United States

Study Locations