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Clinical Trials

MainTitle

Comparison of Tenofovir Vaginal Gel and Film Formulations (FAME-05)

This study has been completed
Sponsor
CONRAD

Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party)
Craig Hendrix, CONRAD

ClinicalTrials.gov Identifier
NCT02280109

First received: October 21, 2014
Last updated: January 27, 2016
Last Verified: January 2016
History of Changes
Purpose

Purpose

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).

Condition Intervention Phase
Healthy
HIV

Drug : Tenofovir Gel
Drug : Tenofovir Film
Early Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Comparison of the Pharmacokinetics and Pharmacodynamics of Single Dose Tenofovir Vaginal Gel and Film Formulation

Further study details as provided by Craig Hendrix, CONRAD:

Primary Outcome Measures

  • Plasma tenofovir concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing [ Time Frame: 72 hours ]
    Concentration-time plot of plasma tenofovir
  • PBMC tenofovir diphosphate concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing [ Time Frame: 72 hours ]
    Concentration-time plot of PBMC tenofovir diphosphate thru 72 hours after dosing
  • Cervical tissue tenofovir maximum concentration (Cmax) at 5 hours [ Time Frame: 5 hours ]
  • Cervical tissue tenofovir maximum concentration (Cmax) at 72 hours [ Time Frame: 72 hours ]
  • Cervical tissue tenofovir diphosphate maximum concentration (Cmax) at 5 hours [ Time Frame: 5 hours ]
  • Cervical tissue tenofovir diphosphate maximum concentration (Cmax) at 72 hours [ Time Frame: 72 hours ]
  • Cervicovaginal fluid tenofovir maximum concentration (Cmax) at 5 hours [ Time Frame: 5 hours ]
  • Cervicovaginal fluid tenofovir maximum concentration (Cmax) at 72 hours [ Time Frame: 72 hours ]
  • Rectal fluid tenofovir maximum concentration (Cmax) at 5 hours [ Time Frame: 5 hours ]
  • Rectal fluid tenofovir maximum concentration (Cmax) at 72 hours [ Time Frame: 72 hours ]
  • All adverse clinical and laboratory events [ Time Frame: one year ]
    Categorize adverse events by treatment formulation to compare the safety of single dose tenofovir gel and film formulations
Secondary Outcome Measures:
  • 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 [ Time Frame: 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 [ Time Frame: 15 days ]

Enrollment: 10
Study Start Date: November 2014
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: Tenofovir Gel
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

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

Other Name: Tenofovir disoproxil
Active Comparator: Tenofovir Film
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

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

Other Name: Tenofovir disoproxil

Detailed Description:

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). Further, pharmacodynamics will be assessed using cervical tissue in an ex vivo HIV biopsy challenge, and safety will be determined by assessment of adverse events following a single dose of each formulation (
Secondary

    objective). The primary endpoint will be to determine concentrations of tenofovir (TFV) and its metabolite, tenofovir diphosphate (TFV-DP), in plasma, tissue homogenates, and cervicovaginal fluid.

Secondary
    endpoints will be determined by assessing concentrations of HIV p24 protein from explant aliquot samples up to 21 days post-infection ex vivo, and by determination of Grade 2 or higher adverse events deemed related to study product.

Research participants will receive the first tenofovir dose formulation prior to the following sampling:
  • Blood PK plasma collection will be obtained at pre-dose, 0.5, 1, 2, 4, 5, 8 and 12 hours (Day 0), 24 hours (Day 1); 48 hours (Day 2); 72 hours (Day 3); and 168 hours (Day 7) following tenofovir formulation dosing.
  • Cervicovaginal fluid sampling, rectal fluid sampling, and cervicovaginal biopsy will be performed (in the sequence listed) 5 and 72 hours after dosing in all subjects. Cervicovaginal fluid and rectal fluid sampling will also be obtained at 168 hours.

Subjects will be counseled to abstain from sexual intercourse and all other insertive vaginal practices for 10 days following each administered dose (or 7 days after the last cervicovaginal sampling at 72 hours). Following a safety evaluation visit, the research participant will return to the research unit and receive a second tenofovir dose formulation followed by the same schedule of sample collection and a final safety visit. PK parameters of TFV and TFV-DP will be estimated and compared between the gel and film formulations. PK parameters will include peak concentration (Cmax), area under the concentration-time curve (AUC), time to peak concentration (Tmax), elimination half-life (t1/2). Tenofovir gel and film ex vivo pharmacodynamics will also be assessed and analyzed for correspondence to pharmacokinetics.
Visit 1 Visits 2-6 Visit 7 Visits 8-12 Visit 13
  • 28 Days Day 0-7 Day 14 Day 28-35 Day 42 These studies will be carried out at The Johns Hopkins Hospital under the direction of Craig Hendrix, MD, as the Project PI.

    Eligibility

    Eligibility

    Ages Eligible for Study: 18 Years to 45 Years  
    Sexes Eligible for Study: Female  
    Accepts Healthy Volunteers: Yes  

    Criteria

    Inclusion Criteria:

    1. 18 to 45 years of age (inclusive) with a history of receptive vaginal intercourse.
    2. HIV negative within 28 days of enrollment
    3. Understand and agree to local STI reporting requirements.
    4. Able and willing to provide written informed consent to take part in the study.
    5. Able and willing to provide adequate information for locator purposes.
    6. Availability to return for all study visits, barring unforeseen circumstances.
    7. 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.
    8. 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.
    9. Willingness to have partner(s) use condoms (must not contain Nonoxynol-9) for the duration of the study.
    10. Agree not to participate in other research studies involving drugs and/or medical devices.
    11. Negative qualitative urine pregnancy test.
    12. Using an effective method of contraception at enrollment.
    13. Willingness to remain in the research unit for up to 12 hours on each of two dosing days.

  • Exclusion Criteria:
  • 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.
  • At screening:
    • ALT or AST greater than 1.5 X the site laboratory ULN
    • Hemoglobin less than 10.0 g/dL
    • Platelet count less than 100,000/mm3
    • Other safety tests outside of the normal range
    • Findings that are clinically significant in the opinion of the investigator
  • Estimated creatinine clearance < 60 ml/min based on established nomograms
  • Recent history (past 6 months) of injection drug use or alcohol use that may interfere with the study.
  • Unwillingness to refrain from aspirin and NSAIDs product use for one week prior to and one week post study procedures.
  • Use of warfarin or heparin.
  • Use of systemic immunomodulatory medications within 4 weeks of enrollment.
  • Use of product containing nonoxynol-9 within 4 weeks of enrollment.
  • Use of any investigational products within 4 weeks of enrollment.
  • Any other medical conditions deemed not safe for participation by the investigator.
  • Any individual that is pregnant or is actively breast feeding.
  • Post-menopausal defined as 12 months of amenorrhea.

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT02280109

    Locations

    United States, Maryland
    Johns Hopkins University School of Medicine Division of Clinical Pharmacology
    Baltimore, Maryland, United States, 21287-5554

    Sponsors and Collaborators

    CONRAD
    National Institute of Allergy and Infectious Diseases (NIAID)

    Investigators

    Principal Investigator: Craig W Hendrix, MD Johns Hopkins University
    More Information

    More Information


    Responsible Party: Craig Hendrix, Professor of Medicine, Pharmacology and Molecular Sciences, Division of Clinical Pharmacology Johns Hopkins University School of Medicine, CONRAD  
    ClinicalTrials.gov Identifier: NCT02280109   History of Changes  
    Other Study ID Numbers: DAIDS-ES #12015  
      U19AI082639  
    Study First Received: October 21, 2014  
    Last Updated: January 27, 2016  

    Keywords provided by Craig Hendrix, CONRAD:

    Tenofovir
    Healthy Volunteers
    HIV
    pharmacokinetics of tenofovir gel and film

    Additional relevant MeSH terms:
    Tenofovir

    ClinicalTrials.gov processed this data on October 16, 2017
    This information is provided by ClinicalTrials.gov.