In Vivo Drug Interaction Pharmacokinetic Study of Tenofovir 1% Gel and Three Commonly Used Vaginal Products
Condition: HIV Prevention
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is determine if the local release characteristics and systemic
      exposure to tenofovir (TFV) 1% gel and a given commonly used vaginal product are impacted by
      concomitant use
    

Detailed description: 
      This study consists of three separate crossover studies, each evaluating if local release
      characteristics and systemic exposure to TFV 1% gel and a given vaginal product are impacted
      by concomitant use. Vaginal products to be assessed are: antifungal cream, antimicrobial gel,
      and the combination contraceptive vaginal ring (IVR). There will be no comparison between
      vaginal product groups.

      Participants will be randomized to vaginal product. Participants in the cream and gel cohorts
      will be randomized to the order of treatment conditions (TFV gel alone, vaginal product
      alone, and TFV gel and vaginal product concomitantly). Participants in the IVR cohort will
      use TFV gel alone during the first crossover period; the order of the remaining treatment
      conditions (IVR alone, TFV and IVR concomitantly) for crossover periods 2 and 3 will be
      randomly assigned.

      Each participant will attend a total of at least 7 visits. At the first visit, volunteers
      will be consented and will undergo procedures to assess whether they are eligible to continue
      in the study. If eligible, they will undergo 3 crossover treatment periods. Within each
      crossover treatment period there will be 2 visits, which will be scheduled to occur within
      the same menstrual cycle; the first visit will be in the follicular phase of the menstrual
      cycle such that product use is initiated on cycle day 9 to 18 and the second visit will be on
      cycle day 16 to 24.

      At the start of crossover period 1, after it has been confirmed that the participant meets
      all of the inclusion criteria and none of the exclusion criteria, she will be randomized to a
      vaginal product cohort and to a sequence of the treatment conditions for the 3 crossover
      periods. Crossover periods 2 and 3 will be scheduled in the subsequent menstrual cycles, with
      the first visit of each crossover period occurring approximately 2 weeks after the completion
      of the previous crossover period.

      Product usage during the 3 crossover periods is as follows:

        -  Treatment Condition (vaginal product alone): The participant will be instructed to use
           her assigned product for 5 to 21 days, depending on the dosing instructions for the
           particular product cohort to which she has been assigned . The second visit of the
           crossover period will occur after product use is complete. For participants using
           antifungal cream or antimicrobial gel, blood specimens will be collected approximately 6
           hours after the last gel or cream use. In the IVR cohort, blood specimens will be
           collected after 21 days of use at 0/4, 6, 10, and 24 hours. The 0/4 hour collection time
           point is the time of the first plasma draw. It is meant to mimic the 4 hour post-TFV gel
           insertion collection time point described below for the TFV gel alone and the vaginal
           product/TFV gel treatment conditions. No biopsies will be collected during the vaginal
           product treatment condition for all cohorts.

        -  Treatment Condition (TFV gel alone): The participant will be instructed to use TFV gel
           for 7 days, inserted twice a day with each dose approximately 12 hours apart. The second
           visit of the crossover period will occur after product use is complete. Blood specimens
           will be collected approximately 4 hours after the last dose of TFV gel. In the IVR
           cohort, participants will have blood specimens collected 4, 6, 10 and 24 hours after the
           last dose of TFV gel. Vaginal biopsy will be scheduled to take place approximately 6
           hours after the last dose of TFV gel for all cohorts.

        -  Treatment Condition (vaginal product and TFV gel): The participant will be instructed to
           use her assigned product for 5 to 21 days, depending on the dosing instructions for the
           particular product cohort to which she has been assigned. TFV gel will be used for 7
           days, inserted twice a day with each dose approximately 12 hours apart; the morning
           insertion of TFV gel will occur approximately two hours after insertion of the vaginal
           product (for the gel and cream cohorts). The second visit of the crossover period will
           occur after product use is complete. In the gel and or cream cohorts, blood specimens
           will be collected approximately 4 hours after the last TFV gel use. In the IVR cohort,
           blood specimens will be collected 4, 6, 10 and 24 hours after the last dose of TFV gel.
           Vaginal biopsy will be scheduled to take place approximately 6 hours after the last dose
           of TFV gel for all cohorts.

      Each participant will be contacted by phone approximately 1-2 weeks after completion of
      crossover period 3 to confirm that there have been no additional adverse experiences. If
      necessary, she may be seen in an unscheduled visit for follow-up. She will then be exited
      from the study.
    

Intervention name(s): Tenofovir 1% gel; Vaginal product
Intervention type(s): Drug; Drug
Other intervention name(s): Terconazole 0.4%; Metronidazole gel; Contraceptive IVR
Intervention MeSH terms: Tenofovir; Metronidazole; Terconazole; Contraceptive Agents
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)