<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01694407</url>
  </required_header>
  <id_info>
    <org_study_id>A11-117</org_study_id>
    <nct_id>NCT01694407</nct_id>
  </id_info>
  <brief_title>Safety, Pharmacokinetics, Pharmacodynamics, and Disintegration Time of Vaginal Tablets Containing Tenofovir and/or Emtricitabine</brief_title>
  <official_title>A Phase I Clinical Trial Assessing the Safety, Pharmacokinetics, Pharmacodynamics, and Disintegration Time of Vaginal Tablets Containing Tenofovir and/or Emtricitabine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CONRAD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CONRAD</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This prospective, double-blinded, randomized, parallel cohort study will examine the genital&#xD;
      and systemic safety, pharmacokinetics (PK), pharmacodynamics (PD), disintegration and&#xD;
      disappearance times, and acceptability of four vaginal tablets: 1) Tenofovir (TFV) alone; 2)&#xD;
      Emtricitabine (FTC) alone; 3) TFV combined with FTC; and 4) placebo. Participants will be&#xD;
      randomized to treatment group, to number of tablets to be inserted in the Single Use Phase (1&#xD;
      tablet or 1 tablet followed by a second tablet two hours later to mimic the BAT24 dosing&#xD;
      regimen), and to one of four collection time points (2, 4, 6, or 24 hours after tablet&#xD;
      insertion) for assessments only after the last dose of the Multiple Use Phase.&#xD;
&#xD;
      In the Single Use Phase of the study, the participant will insert one tablet in the clinic to&#xD;
      estimate times to disintegration and disappearance. Those randomized to two tablets will&#xD;
      insert a second tablet 2 hours later. In all women, sample collection will occur 5 hours&#xD;
      after the initial tablet insertion.&#xD;
&#xD;
      In the Multiple Use Phase of the study, participants will insert a tablet once daily for 14&#xD;
      days. The 1st, 7th, and 14th tablets will be inserted in the clinic; the remaining tablets&#xD;
      will be inserted at home. The clinic will call the participant on day 3 of the multiple use&#xD;
      phase to ask about any symptoms the participant may be experiencing. Each insertion in the&#xD;
      clinic will be followed by sample collection and, at Visits 4 and 6, colposcopy at the&#xD;
      participant's assigned time point.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
&#xD;
      Primary:&#xD;
&#xD;
        -  To assess genital safety after a single use (consisting of one tablet in half of&#xD;
           participants and one tablet followed by a second tablet two hours later in the other&#xD;
           half) and during and after two weeks of daily tablet use&#xD;
&#xD;
        -  To assess systemic safety after two weeks of daily tablet use&#xD;
&#xD;
        -  To assess the pharmacokinetics (PK) of TFV and FTC after a single use (as defined above)&#xD;
           and during and after two weeks of daily tablet use&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
        -  To estimate the time needed for tablet disintegration and the time needed for full&#xD;
           tablet disappearance&#xD;
&#xD;
        -  To assess acceptability of the tablet&#xD;
&#xD;
        -  To assess indicators of the pharmacodynamics (PD) of TFV and FTC in vitro using&#xD;
           biological samples (fluids) from study participants obtained before use, after a single&#xD;
           (use as define above), and after two weeks of daily tablet use&#xD;
&#xD;
      Exploratory:&#xD;
&#xD;
      •To assess exploratory indicators of the PD of TFV and FTC in vitro using biological samples&#xD;
      (tissues) from study participants obtained before use, after a single use (as defined above),&#xD;
      and after two weeks of daily tablet use&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Genitourinary AEs</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Genitourinary AEs, moderate to severe</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes on physical examination and colposcopy</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Changes on physical examination and colposcopy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes Soluble markers of mucosal immunity, immune cell numbers, &amp; characteristics in CVL</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Changes Soluble markers of mucosal immunity, immune cell numbers, &amp; characteristics in CVL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Number, phenotype and activation status of immune cells in cervicovaginal mucosa</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Changes in Number, phenotype and activation status of immune cells in cervicovaginal mucosa</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Mucosal histology in cervicovaginal tissue</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Changes in Mucosal histology in cervicovaginal tissue</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Changes in microflora</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Changes in Changes in microflora (semiquantitative cultures and unculturable species)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Systemic laboratory tests</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Changes in Systemic laboratory tests</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TFV &amp; FTC concentrations in plasma, vaginal aspirate, &amp; genital tissue</measure>
    <time_frame>5 hours after first tablet insertion</time_frame>
    <description>TFV &amp; FTC concentrations in plasma, vaginal aspirate, &amp; 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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, &amp; genital tissue</measure>
    <time_frame>5 hours after first tablet insertion</time_frame>
    <description>TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, &amp; genital tissue Pharmacokinetics C-Max and T-Max of Blood TFV and FTC levels at single dose phase, by site and overall, Evaluable Population</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TFV &amp; FTC concentrations in plasma, vaginal aspirate, &amp; genital tissue</measure>
    <time_frame>after 7th daily tablet</time_frame>
    <description>TFV &amp; FTC concentrations in plasma, vaginal aspirate, &amp; 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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TFV &amp; FTC concentrations in plasma, vaginal aspirate, &amp; genital tissue</measure>
    <time_frame>after 14 daily tablet insertion</time_frame>
    <description>TFV &amp; FTC concentrations in plasma, vaginal aspirate, &amp; 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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, &amp; genital tissue</measure>
    <time_frame>after 7th daily tablet</time_frame>
    <description>TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, &amp; genital tissue Pharmacokinetics C-Max and T-Max of Blood TFV and FTC levels at single dose phase, by site and overall, Evaluable Population</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, &amp; genital tissue</measure>
    <time_frame>after 14th daily tablet</time_frame>
    <description>TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, &amp; genital tissue Pharmacokinetics C-Max and T-Max of Blood TFV and FTC levels at single dose phase, by site and overall, Evaluable Population</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Anti-HIV and anti-HSV activity in CVL&#xD;
Anti-HIV and anti-HSV activity as a percent of anti-HIV and anti-HSV activity before exposure to test product</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disintegration</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Medians and interquartile ranges of (a) time to disintegration (tablet no longer coherent but residual product is visible) and (b) time to complete disappearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability</measure>
    <time_frame>5 hours after first tablet insertion and after 7th and 14th daily tablet</time_frame>
    <description>Responses on acceptability questionnaires</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>TFV Alone Vaginal Tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Emtricitabine (FTC) Alone Vaginal Tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TFV Combined with FTC Vaginal Tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Vaginal Tablet</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir (TFV) Alone Vaginal Tablet</intervention_name>
    <description>vaginal tablet containing 40 mg of TFV</description>
    <arm_group_label>TFV Alone Vaginal Tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Emtricitabine (FTC) Alone Vaginal Tablet</intervention_name>
    <description>Vaginal Tablet containing 40 mg of TFV</description>
    <arm_group_label>Emtricitabine (FTC) Alone Vaginal Tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TFV and FTC Combined Vaginal Tablet</intervention_name>
    <description>vaginal tablet with 40 mg TFV and 40 mg FTC</description>
    <arm_group_label>TFV Combined with FTC Vaginal Tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Vaginal Tablet</intervention_name>
    <description>Vaginal Tablet containing no drug</description>
    <arm_group_label>Placebo Vaginal Tablet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  General good health (by volunteer history and per investigator discretion) without any&#xD;
             clinically significant systemic disease (including, but not limited to significant&#xD;
             liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease,&#xD;
             osteoporosis or bone disease, and diabetes)&#xD;
&#xD;
          -  Currently having regular menstrual cycles of 25 - 35 days by participant report&#xD;
&#xD;
          -  History of Pap smears and follow-up consistent with American Congress of Obstetricians&#xD;
             and Gynecologist (ACOG) practice guidelines #99 and #109 or willing to undergo a Pap&#xD;
             smear at Visit 1&#xD;
&#xD;
          -  Protected from pregnancy, meaning one of the following:&#xD;
&#xD;
               -  Sexually abstinent and planning to remain abstinent for the duration of the&#xD;
                  study;&#xD;
&#xD;
               -  In a monogamous heterosexual relationship for at least four months with a partner&#xD;
                  who is not known to be HIV positive and has no known risks for sexually&#xD;
                  transmitted infections (STIs) and:&#xD;
&#xD;
          -  Couple is using condoms and is willing to use non-spermicidally lubricated condoms&#xD;
             throughout the study or&#xD;
&#xD;
          -  One partner is sterilized; or&#xD;
&#xD;
               -  In a monogamous same sex relationship for at least four months with a partner who&#xD;
                  is not known to be HIV positive and has no known risks for STIs.&#xD;
&#xD;
          -  Willing to abstain from vaginal activity as follows:&#xD;
&#xD;
        Starting 48 hours before Visit 2 until the sixth day after Visit 2 Starting 48 hours before&#xD;
        Visit 3 until the sixth day after Visit 3 Starting 48 hours before Visit 4 until the sixth&#xD;
        day after Visit 6&#xD;
&#xD;
          -  Willing to abstain from the use of any vaginal product other than the study product&#xD;
             including spermicides, lubricants, and douches starting 48 hours before Visit 2 until&#xD;
             the sixth day after Visit 6 (tampons may be used, but for menses only)&#xD;
&#xD;
          -  Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to&#xD;
             easy colposcopy and genital tract sample collection&#xD;
&#xD;
          -  Negative urine pregnancy test&#xD;
&#xD;
          -  Willing to give voluntary consent, sign an informed consent form and comply with study&#xD;
             procedures as required by the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hysterectomy&#xD;
&#xD;
          -  Currently pregnant or within two calendar months from the last pregnancy outcome.&#xD;
             Note: If recently pregnant must have had at least two spontaneous menses since&#xD;
             pregnancy outcome&#xD;
&#xD;
          -  Use of any hormonal contraceptive method in the last 30 days (oral, transdermal,&#xD;
             transvaginal, implant, or hormonal intrauterine contraceptive device)&#xD;
&#xD;
          -  Injection of Depo-Provera in the last 6 months&#xD;
&#xD;
          -  Current use of IUD&#xD;
&#xD;
          -  Currently breastfeeding or having breastfed an infant in the last two months, or&#xD;
             planning to breastfeed during the course of the study&#xD;
&#xD;
          -  History of sensitivity/allergy to any component of the study products, topical&#xD;
             anesthetic, or allergy to both silver nitrate and Monsel's solution&#xD;
&#xD;
          -  In the last six months, diagnosed with or treated for any STI or pelvic inflammatory&#xD;
             disease. Note: Women with a history of genital herpes or condylomata who have been&#xD;
             asymptomatic for at least six months may be considered for eligibility&#xD;
&#xD;
          -  Nugent score greater than or equal to 7 at Visit 1 or symptomatic bacterial vaginosis&#xD;
             (BV) as defined by Amsel's criteria at Visit 1 or 2&#xD;
&#xD;
          -  Symptomatic vulvovaginal candidiasis or symptomatic urinary tract infection (UTI)&#xD;
&#xD;
          -  Positive test for Trichomonas vaginalis, Neisseria gonorrhea or Chlamydia trachomatis&#xD;
&#xD;
          -  Deep epithelial genital findings such as abrasions, ulcerations, and lacerations, or&#xD;
             vesicles suspicious for an STI&#xD;
&#xD;
          -  Positive test for HIV&#xD;
&#xD;
          -  Positive test for Hepatitis B surface antigen (HBsAg)&#xD;
&#xD;
          -  Known bleeding disorder that could lead to prolonged or continuous bleeding with&#xD;
             biopsy&#xD;
&#xD;
          -  Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting, etc.)&#xD;
&#xD;
          -  Known current drug or alcohol abuse which could impact study compliance&#xD;
&#xD;
          -  Grade 1 or higher laboratory abnormality, per the August 2009 update of the Division&#xD;
             of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for&#xD;
             Grading the Severity of Adverse Events (AEs)&#xD;
&#xD;
          -  Systemic use in the last two weeks or anticipated use during the study of any of the&#xD;
             following: corticosteroids, antibiotics, antifungals, antivirals (e.g., acyclovir or&#xD;
             valacyclovir) or antiretrovirals (e.g., Viread, Atripla, Emtriva, Complera). Note:&#xD;
             Participants should avoid non-steroidal anti-inflammatory drugs (NSAIDs) except for&#xD;
             treatment of dysmenorrhea during menses. Participants may use Tylenol® on an as-needed&#xD;
             but not daily basis during the study.&#xD;
&#xD;
          -  Participation in any other investigational trial (device, drug, or vaginal trial)&#xD;
             within the last 30 days or planned participation in any other investigational trial&#xD;
             during the study&#xD;
&#xD;
          -  History of gynecological procedures (including genital piercing) on the external&#xD;
             genitalia, vagina or cervix within the last 14 days&#xD;
&#xD;
          -  Abnormal finding on laboratory or physical examination or a social or medical&#xD;
             condition which, in the opinion of the investigator, would make participation in the&#xD;
             study unsafe or would complicate interpretation of data&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jill Schwartz, MD</last_name>
    <role>Study Director</role>
    <affiliation>CONRAD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Albert Einstein College of Medicine</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Center, Eastern Virginia Medical School</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>July 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>March 31, 2015</last_update_submitted>
  <last_update_submitted_qc>March 31, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prevention</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Emtricitabine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01694407
org study id: A11-117
nct id: NCT01694407
lead sponsor: 
has dmc: No
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Outcomes Assessor)
measure: Changes in Genitourinary AEs
time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
description: Genitourinary AEs, moderate to severe
measure: Changes on physical examination and colposcopy
time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
description: Changes on physical examination and colposcopy
measure: 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
description: Changes Soluble markers of mucosal immunity, immune cell numbers, & characteristics in CVL
measure: 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
description: Changes in Number, phenotype and activation status of immune cells in cervicovaginal mucosa
measure: Changes in Mucosal histology in cervicovaginal tissue
time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
description: Changes in Mucosal histology in cervicovaginal tissue
measure: Changes in Changes in microflora
time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
description: Changes in Changes in microflora (semiquantitative cultures and unculturable species)
measure: Changes in Systemic laboratory tests
time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
description: Changes in Systemic laboratory tests
measure: TFV & FTC concentrations in plasma, vaginal aspirate, & genital tissue
time frame: 5 hours after first tablet insertion
description: 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
measure: TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, & genital tissue
time frame: 5 hours after first tablet insertion
description: 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
measure: TFV & FTC concentrations in plasma, vaginal aspirate, & genital tissue
time frame: after 7th daily tablet
description: 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
measure: TFV & FTC concentrations in plasma, vaginal aspirate, & genital tissue
time frame: after 14 daily tablet insertion
description: 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
measure: TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, & genital tissue
time frame: after 7th daily tablet
description: 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
measure: TFV-DP and FTC-TP concentrations in PBMCs, endocervical cells, & genital tissue
time frame: after 14th daily tablet
description: 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
measure: Pharmacodynamics
time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
description: 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
measure: Disintegration
time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
description: Medians and interquartile ranges of (a) time to disintegration (tablet no longer coherent but residual product is visible) and (b) time to complete disappearance
measure: Acceptability
time frame: 5 hours after first tablet insertion and after 7th and 14th daily tablet
description: Responses on acceptability questionnaires
arm group label: TFV Alone Vaginal Tablet
arm group type: Active Comparator
arm group label: Emtricitabine (FTC) Alone Vaginal Tablet
arm group type: Active Comparator
arm group label: TFV Combined with FTC Vaginal Tablet
arm group type: Active Comparator
arm group label: Placebo Vaginal Tablet
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Tenofovir (TFV) Alone Vaginal Tablet
description: vaginal tablet containing 40 mg of TFV
arm group label: TFV Alone Vaginal Tablet
intervention type: Drug
intervention name: Emtricitabine (FTC) Alone Vaginal Tablet
description: Vaginal Tablet containing 40 mg of TFV
arm group label: Emtricitabine (FTC) Alone Vaginal Tablet
intervention type: Drug
intervention name: TFV and FTC Combined Vaginal Tablet
description: vaginal tablet with 40 mg TFV and 40 mg FTC
arm group label: TFV Combined with FTC Vaginal Tablet
intervention type: Drug
intervention name: Placebo Vaginal Tablet
description: Vaginal Tablet containing no drug
arm group label: Placebo Vaginal Tablet
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jill Schwartz, MD
role: Study Director
affiliation: CONRAD
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tenofovir
mesh term: Emtricitabine