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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
48
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
Albert Einstein College of Medicine
The Bronx, New York, United States
Clinical Research Center, Eastern Virginia Medical School
Norfolk, Virginia, United States
Changes in Genitourinary AEs
Genitourinary AEs, moderate to severe
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
Changes on physical examination and colposcopy
Changes on physical examination and colposcopy
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
Changes Soluble markers of mucosal immunity, immune cell numbers, & characteristics in CVL
Changes Soluble markers of mucosal immunity, immune cell numbers, \& characteristics in CVL
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
Changes in Number, phenotype and activation status of immune cells in cervicovaginal mucosa
Changes in Number, phenotype and activation status of immune cells in cervicovaginal mucosa
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
Changes in Mucosal histology in cervicovaginal tissue
Changes in Mucosal histology in cervicovaginal tissue
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
Changes in Changes in microflora
Changes in Changes in microflora (semiquantitative cultures and unculturable species)
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
Changes in Systemic laboratory tests
Changes in Systemic laboratory tests
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
TFV & FTC concentrations in plasma, vaginal aspirate, & genital tissue
TFV \& FTC concentrations in plasma, vaginal aspirate, \& genital tissue Pharmacokinetics Mean (SD) and Median (Min, Max, C-Max, T-Max) of TFV and FTC in blood, vaginal aspirate,and genital tissue at Visit 2, 3, 4, 5, 6
Time frame: 5 hours after first tablet insertion
TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, & genital tissue
TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, \& genital tissue Pharmacokinetics C-Max and T-Max of Blood TFV and FTC levels at single dose phase, by site and overall, Evaluable Population
Time frame: 5 hours after first tablet insertion
TFV & FTC concentrations in plasma, vaginal aspirate, & genital tissue
TFV \& FTC concentrations in plasma, vaginal aspirate, \& genital tissue Pharmacokinetics Mean (SD) and Median (Min, Max, C-Max, T-Max) of TFV and FTC in blood, vaginal aspirate,and genital tissue at Visit 2, 3, 4, 5, 6
Time frame: after 7th daily tablet
TFV & FTC concentrations in plasma, vaginal aspirate, & genital tissue
TFV \& FTC concentrations in plasma, vaginal aspirate, \& genital tissue Pharmacokinetics Mean (SD) and Median (Min, Max, C-Max, T-Max) of TFV and FTC in blood, vaginal aspirate,and genital tissue at Visit 2, 3, 4, 5, 6
Time frame: after 14 daily tablet insertion
TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, & genital tissue
TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, \& genital tissue Pharmacokinetics C-Max and T-Max of Blood TFV and FTC levels at single dose phase, by site and overall, Evaluable Population
Time frame: after 7th daily tablet
TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, & genital tissue
TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, \& genital tissue Pharmacokinetics C-Max and T-Max of Blood TFV and FTC levels at single dose phase, by site and overall, Evaluable Population
Time frame: after 14th daily tablet
Pharmacodynamics
Anti-HIV and anti-HSV activity in CVL Anti-HIV and anti-HSV activity as a percent of anti-HIV and anti-HSV activity before exposure to test product
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
Disintegration
Medians and interquartile ranges of (a) time to disintegration (tablet no longer coherent but residual product is visible) and (b) time to complete disappearance
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
Acceptability
Responses on acceptability questionnaires
Time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
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