Comparison of Tenofovir Vaginal Gel and Film Formulations
Condition: Healthy; HIV
Study type: Interventional
Phase: Early Phase 1

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).
    

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.
    

Intervention name(s): Tenofovir Gel; Tenofovir Film
Intervention type(s): Drug; Drug
Intervention description(s): single dose of 1% tenofovir gel (equivalent to 40 mg in 4ml's of gel); single dose of 1.3% tenofovir film (equivalent to 40 mg)
Other intervention name(s): Tenofovir disoproxil; Tenofovir disoproxil
Intervention MeSH terms: Tenofovir
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Tenofovir; Healthy Volunteers; HIV; pharmacokinetics of tenofovir gel and film