Safety, Pharmacokinetics, Pharmacodynamics, and Disintegration Time of Vaginal Tablets Containing Tenofovir and/or Emtricitabine
Condition: HIV
Study type: Interventional
Phase: Phase 1

Summary: 
      This prospective, double-blinded, randomized, parallel cohort study will examine the genital
      and systemic safety, pharmacokinetics (PK), pharmacodynamics (PD), disintegration and
      disappearance times, and acceptability of four vaginal tablets: 1) Tenofovir (TFV) alone; 2)
      Emtricitabine (FTC) alone; 3) TFV combined with FTC; and 4) placebo. Participants will be
      randomized to treatment group, to number of tablets to be inserted in the Single Use Phase (1
      tablet or 1 tablet followed by a second tablet two hours later to mimic the BAT24 dosing
      regimen), and to one of four collection time points (2, 4, 6, or 24 hours after tablet
      insertion) for assessments only after the last dose of the Multiple Use Phase.

      In the Single Use Phase of the study, the participant will insert one tablet in the clinic to
      estimate times to disintegration and disappearance. Those randomized to two tablets will
      insert a second tablet 2 hours later. In all women, sample collection will occur 5 hours
      after the initial tablet insertion.

      In the Multiple Use Phase of the study, participants will insert a tablet once daily for 14
      days. The 1st, 7th, and 14th tablets will be inserted in the clinic; the remaining tablets
      will be inserted at home. The clinic will call the participant on day 3 of the multiple use
      phase to ask about any symptoms the participant may be experiencing. Each insertion in the
      clinic will be followed by sample collection and, at Visits 4 and 6, colposcopy at the
      participant's assigned time point.
    

Detailed description: 
      Objectives:

      Primary:

        -  To assess genital safety after a single use (consisting of one tablet in half of
           participants and one tablet followed by a second tablet two hours later in the other
           half) and during and after two weeks of daily tablet use

        -  To assess systemic safety after two weeks of daily tablet use

        -  To assess the pharmacokinetics (PK) of TFV and FTC after a single use (as defined above)
           and during and after two weeks of daily tablet use

      Secondary:

        -  To estimate the time needed for tablet disintegration and the time needed for full
           tablet disappearance

        -  To assess acceptability of the tablet

        -  To assess indicators of the pharmacodynamics (PD) of TFV and FTC in vitro using
           biological samples (fluids) from study participants obtained before use, after a single
           (use as define above), and after two weeks of daily tablet use

      Exploratory:

      •To assess exploratory indicators of the PD of TFV and FTC in vitro using biological samples
      (tissues) from study participants obtained before use, after a single use (as defined above),
      and after two weeks of daily tablet use
    

Intervention name(s): Tenofovir (TFV) Alone Vaginal Tablet; Emtricitabine (FTC) Alone Vaginal Tablet; TFV and FTC Combined Vaginal Tablet; Placebo Vaginal Tablet
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): vaginal tablet containing 40 mg of TFV; Vaginal Tablet containing 40 mg of TFV; vaginal tablet with 40 mg TFV and 40 mg FTC; Vaginal Tablet containing no drug
Intervention MeSH terms: Tenofovir; Emtricitabine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Prevention