Coital Pharmacokinetics/Pharmacodynamics (PK/PD) of Tenofovir Gel

Summary

Study Objectives:

* To assess the impact of coitus (and semen) on the pharmacokinetics of tenofovir 1% gel in female genital tract secretions, vaginal and cervical tissue and rectal tract secretions
* To assess the impact of coitus (and semen) on pharmacodynamics of luminal drug by measuring the anti-HIV-1 activity in CVL samples

Study Summary:

MTN-011 will enroll heterosexual monogamous, sexually active couples, in which both partners are healthy and HIV-negative. The female participants must be between the ages of 21-46 (inclusive) and currently using effective non-barrier contraception. Male participants must be 21 years of age or older. This Phase 1 expanded safety study will assess tenofovir PK in the genital tract secretions (CVL), rectal (rectal sponge) and both intracellular and extracellular tissue compartments (vaginal biopsy) in the absence of, or following coitus. Pharmacodynamics (antiviral activity) will also be assessed in CVL. MTN-011 will study the timing in which coitus might have the greatest impact on these variables, which is when gel is applied shortly prior to coitus in the absence of a drug reservoir.

MTN-011 will examine PK/PD in response to a single dose of 1% tenofovir gel applied shortly before sex and compare to PK/PD assessments following a single gel application without sex. Additionally, data obtained from a visit in which participants do not dose with gel and do not have sex will serve as an additional control for the pharmacodynamic (PD) studies of the antiviral activity in CVL. If tenofovir retains its antiviral activity following sex, then the anti-HIV activity in CVL collected at the visit in which female participants dose with gel and have sex should be comparable to that of CVL collected at the visit in which females dose with gel and then do not engage in intercourse and significantly greater than the endogenous anti-HIV activity in CVL obtained at the visit in which participants do not dose with gel but do have sex and the visit in which no gel is administered and sex does occur. Data analysis performed after the completion of enrollment and follow-up procedures will demonstrate if there is an impact of coitus and semen on PK/PD when a single 1% tenofovir dose is applied shortly prior to sex.

Conditions

• Pharmacokinetics of 1% Tenofovir Gel Following Coitus
• Pharmacodynamics of 1% Tenofovir Gel Following Coitus

Interventions

DRUG

1% Tenofovir Gel

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• National Institute of Mental Health (NIMH)

  collaborator NIH

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• CONRAD

  lead OTHER

Principal Investigators

• Betsy Herold, MD · Albert Einstein College of Medicine

• Beatrice A. Chen, MD, MPH · University of Pittsburgh

• Robert A. Salata, MD · Case Western Reserve University

Study Design

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

46 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-11-30

Primary Completion

2014-06-30

Completion

2014-11-30

Countries

• United States

Study Locations