Comparison of Tenofovir Vaginal Gel and Film Formulations

NCT02280109 | Completed Early Phase 1

• 2 other identifiers: DAIDS-ES #12015U19AI082639
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label comparative study of tenofovir gel and film in 10 healthy sexually active women without active female genital tract disorders. The women will receive a single dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and tenofovir film (1.3%;40 mg) - in a crossover study design to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid (primary objective).

Conditions

Healthy; HIV

Keywords

Tenofovir; Healthy Volunteers; HIV; pharmacokinetics of tenofovir gel and film

Outcome Measures

Primary Outcomes (11)

• Plasma tenofovir concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing

  Concentration-time plot of plasma tenofovir

  72 hours

• PBMC tenofovir diphosphate concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing

  Concentration-time plot of PBMC tenofovir diphosphate thru 72 hours after dosing

  72 hours

• Cervical tissue tenofovir maximum concentration (Cmax) at 5 hours

  5 hours

• Cervical tissue tenofovir maximum concentration (Cmax) at 72 hours

  72 hours

• Cervical tissue tenofovir diphosphate maximum concentration (Cmax) at 5 hours

  5 hours

• Cervical tissue tenofovir diphosphate maximum concentration (Cmax) at 72 hours

  72 hours

• Cervicovaginal fluid tenofovir maximum concentration (Cmax) at 5 hours

  5 hours

• Cervicovaginal fluid tenofovir maximum concentration (Cmax) at 72 hours

  72 hours

• Rectal fluid tenofovir maximum concentration (Cmax) at 5 hours

  5 hours

• Rectal fluid tenofovir maximum concentration (Cmax) at 72 hours

  72 hours

• All adverse clinical and laboratory events

  Categorize adverse events by treatment formulation to compare the safety of single dose tenofovir gel and film formulations

  one year

Secondary Outcomes (2)

• Cumulative HIV p24 protein concentration from 0 to 15 days post ex-vivo infection of explant cervical tissue collected at 5 hours after dosing with tenofovir gel or film

  15 days

• Cumulative HIV p24 protein concentration from 0 to 15 days post ex-vivo infection of explant cervical tissue collected at 72 hours after dosing with tenofovir gel or film

  15 days

Study Arms (2)

Tenofovir Gel

ACTIVE COMPARATOR

Women will receive a single dose of tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid.

Drug: Tenofovir Gel

Tenofovir Film

ACTIVE COMPARATOR

Women will receive a single dose of tenofovir film (1.3%;40 mg) to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid.

Drug: Tenofovir Film

Interventions

Tenofovir Gel DRUG

single dose of 1% tenofovir gel (equivalent to 40 mg in 4ml's of gel)

Also known as: Tenofovir disoproxil

Tenofovir Gel

Tenofovir Film DRUG

single dose of 1.3% tenofovir film (equivalent to 40 mg)

Also known as: Tenofovir disoproxil

Tenofovir Film

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 45 years of age (inclusive) with a history of receptive vaginal intercourse.
• HIV negative within 28 days of enrollment
• Understand and agree to local STI reporting requirements.
• Able and willing to provide written informed consent to take part in the study.
• Able and willing to provide adequate information for locator purposes.
• Availability to return for all study visits, barring unforeseen circumstances.
• Availability to return for the second formulation dosing at the same time in the subject's menstrual cycle as when the first formulation was administered, at least 10 days before menses.
• Willing to abstain from vaginal intercourse and insertion of anything (e.g., drug, vaginal douche, personal lubricant or sex toy) in vagina for 72 hours before each study product exposure, and 10 days following study product dosing, comprising a total of 26 days of abstinence, no insertion of vaginal products/objects while participating in the study.
• Willingness to have partner(s) use condoms (must not contain Nonoxynol-9) for the duration of the study.
• Agree not to participate in other research studies involving drugs and/or medical devices.
• Negative qualitative urine pregnancy test.
• Using an effective method of contraception at enrollment.
• Willingness to remain in the research unit for up to 12 hours on each of two dosing days.

You may not qualify if:

• Current sexual partner known by participant to be HIV seropositive.
• Individuals who, by history, engage in condom-less intercourse with HIV-infected partners, or partners that have unknown HIV serostatus, or women who exchange sex for money, shelter, or gifts.
• Active chlamydia, gonorrhea, syphilis, trichomonas, cervicitis or PID within 8 weeks prior to enrollment.
• Individuals with active hepatitis B infection.
• Known history of genital HSV (diagnosed by either clinical or laboratory test).
• Symptomatic vaginal candidiasis or bacterial vaginosis.
• Undiagnosed irregular uterine bleeding
• Pathology of the female genital tract,
• Individuals who are status post hysterectomy.
• History of any cervicovaginal procedure (i.e. colposcopy with cervical biopsy) within the past 2 months.
• History of cone biopsy or extensive loop electrosurgical excision procedure (LEEP), which in the judgment of the investigator may affect permeability assessment.
• Any known primary or secondary uro-genital malformations, which in the assessment of the investigator may interfere with the intended urine collection for PK studies.
• Use of vaginally administered medications within 4 week of enrollment
• Any active urinary tract infection
• By history, subjects with irregular menstrual cycles.

Sponsors & Collaborators

• CONRAD: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Johns Hopkins University School of Medicine Division of Clinical Pharmacology

Baltimore, Maryland, 21287-5554, United States

Location

MeSH Terms

Interventions

Tenofovir

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Craig W Hendrix, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Pharmacology and Molecular Sciences, Division of Clinical Pharmacology Johns Hopkins University School of Medicine

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: October 31, 2014
• Study Start: November 1, 2014
• Primary Completion: December 1, 2015
• Last Updated: January 28, 2016

Record last verified: 2016-01

Locations

US (1)