<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/NCT02235662</url>
  </required_header>
  <id_info>
    <org_study_id>A13-128</org_study_id>
    <nct_id>NCT02235662</nct_id>
  </id_info>
  <brief_title>Phase I One-month Safety, PK, PD, and Acceptability Study of IVR Releasing TFV and LNG or TFV Alone</brief_title>
  <official_title>Phase I One-Month Safety, Pharmacokinetic, Pharmacodynamic, and Acceptability Study of Intravaginal Rings Releasing Tenofovir and Levonorgestrel or Tenofovir Alone</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>
      The purpose of the study is to evaluate the safety of the TFV/LNG intravaginal ring (IVR),&#xD;
      TFV-only IVR, and placebo IVR, evaluate pharmacokinetics (PK) of TFV and LNG, evaluate&#xD;
      pharmacodynamic (PD) surrogates of contraceptive efficacy of LNG, and to evaluate&#xD;
      acceptability of the IVRs.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of treatment-emergent adverse events</measure>
    <time_frame>IVR Day 1, 2, ~8, ~16-18; 24 hours and 1-2 weeks post-IVR insertion and 1-2 weeks after IVR removal</time_frame>
    <description>Number of treatment-emergent adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Systemic laboratory tests</measure>
    <time_frame>Baseline and IVR Day ~16-18</time_frame>
    <description>Changes in Systemic laboratory tests</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cervicovaginal ulcerations, abrasions, edema, and other findings</measure>
    <time_frame>Baseline, IVR Day 2, ~8 and ~16-18</time_frame>
    <description>Development of cervicovaginal ulcerations, abrasions, edema, and other findings as assessed by naked eye and colposcopic visualization of the cervicovaginal epithelium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Soluble markers of innate mucosal immunity and inflammatory response in cervicovaginal lavage (CVL) fluid</measure>
    <time_frame>Baseline and IVR Day ~16-18</time_frame>
    <description>Changes in soluble markers of innate mucosal immunity and inflammatory response in CVL fluid</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HIV-1 target immune cell phenotype and HIV-1 activation/proliferation marker in cervicovaginal tissue (biopsy)</measure>
    <time_frame>Baseline and IVR Day ~16-18</time_frame>
    <description>Changes in HIV-1 target immune cell phenotype and HIV-1 activation/proliferation marker in cervicovaginal tissue (biopsy)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Microflora (semi-quantitative vaginal culture and/or unculturable bacteria)</measure>
    <time_frame>Baseline and IVR Day ~16-18</time_frame>
    <description>Changes microflora (semi-quantitative vaginal culture and/or unculturable bacteria)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vaginal pH</measure>
    <time_frame>Baseline and IVR Day ~16-18</time_frame>
    <description>Changes in vaginal pH</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nugent Score</measure>
    <time_frame>Baseline and IVR Day ~16-18</time_frame>
    <description>Changes in Nugent Score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>TFV concentrations in plasma</measure>
    <time_frame>Baseline; 1, 2, 4 and 8 hrs post-IVR insertion; IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal</time_frame>
    <description>TFV concentrations in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFV concentrations in cervicovaginal fluid (aspirate and swab)</measure>
    <time_frame>1, 2, 4 or 8 hours post-IVR insertion (randomized time point); IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal</time_frame>
    <description>TFV concentrations in cervicovaginal fluid (aspirate and swab)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFV concentrations in genital tissue (biopsy)</measure>
    <time_frame>IVR Day 2, ~16-18; 24 or 72 hours post-IVR removal (randomized time point)</time_frame>
    <description>TFV concentrations in genital tissue (biopsy)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs)</measure>
    <time_frame>IVR Day ~16-18</time_frame>
    <description>TFV-DP concentrations in PBMCs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFV-DP concentrations in genital tissue (biopsy)</measure>
    <time_frame>IVR Day 2, ~16-18; 24 or 72 hours post-IVR removal (randomized time point)</time_frame>
    <description>TFV-DP concentrations in genital tissue (biopsy)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LNG concentration in blood (including SHBG)</measure>
    <time_frame>Baseline; 1, 2, 4 and 8 hrs post-IVR insertion; IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal</time_frame>
    <description>LNG concentration in blood (including SHBG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LNG concentration in vaginal secretions (swabs)</measure>
    <time_frame>Baseline; IVR Day~8</time_frame>
    <description>LNG concentration in vaginal secretions (swabs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LNG concentration in cervical mucus</measure>
    <time_frame>IVR Day ~8, ~16-18; 24 hours post-IVR removal</time_frame>
    <description>LNG concentration in cervical mucus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight of returned IVRs</measure>
    <time_frame>IVR Day ~16-18 (post-removal)</time_frame>
    <description>Weight of returned IVRs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of drug remaining in returned IVRs</measure>
    <time_frame>IVR Day ~16-18 (post-removal)</time_frame>
    <description>Amount of drug remaining in returned IVRs</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cervical mucus assessment and sperm migration on the Simplified Slide test</measure>
    <time_frame>IVR Day ~8</time_frame>
    <description>Surrogates of contraceptive efficacy - Cervical mucus assessment</description>
  </other_outcome>
  <other_outcome>
    <measure>Ovulation by P4</measure>
    <time_frame>IVR Day ~16-18</time_frame>
    <description>Surrogates of contraceptive efficacy - Ovulation by P4</description>
  </other_outcome>
  <other_outcome>
    <measure>Follicular development by serum estradiol concentration</measure>
    <time_frame>IVR Day ~8, ~16-18</time_frame>
    <description>Surrogates of contraceptive efficacy - Follicular development by serum estradiol concentration</description>
  </other_outcome>
  <other_outcome>
    <measure>Acceptability of IVR</measure>
    <time_frame>IVR Day ~16-18 (post-removal)</time_frame>
    <description>Acceptability of IVR as measured by a composite of the following factors: Discontinuations, Expulsions, Removals, Visible changes (such as discoloration) as documented on photographs of returned IVRs, Responses to key questions on acceptability questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacodynamics</measure>
    <time_frame>Baseline, IVR Day ~16-18</time_frame>
    <description>Pharmacodynamics - Anti-herpes simplex virus (HSV)-2 and Anti-HIV-1 activities in the CVL. Anti-HIV and anti-HSV activity as a percent of anti-HIV and anti-HSV activity before exposure to test product</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacodynamics</measure>
    <time_frame>Baseline, IVR Day ~16-18</time_frame>
    <description>TFV anti-HIV efficacy in cervicovaginal tissues. Comparison of cervicovaginal tissue permissiveness to ex vivo infection with HIV-1 BaL between the control cycle and treatment cycle.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacodynamic surrogates of LNG in endometrium</measure>
    <time_frame>Baseline, IVR Day ~16-18</time_frame>
    <description>Findings on endometrial biopsy: Histology, Markers of endometrial function</description>
  </other_outcome>
  <other_outcome>
    <measure>Endometrial thickness</measure>
    <time_frame>Baseline, IVR Day ~16-18</time_frame>
    <description>Endometrial thickness as assessed by transvaginal ultrasound</description>
  </other_outcome>
  <other_outcome>
    <measure>Cervicovaginal epithelial histology and epithelial integrity in cervicovaginal tissue (biopsy)</measure>
    <time_frame>Baseline, IVR Day ~16-18</time_frame>
    <description>Cervicovaginal epithelial histology (thickness and number of cell layers) and epithelial integrity, as measured immuno-histochemistry (IHC) of epithelial junction proteins in cervicovaginal tissue (biopsy)</description>
  </other_outcome>
  <other_outcome>
    <measure>Markers of mucosal alteration and inflammation (e.g., expression of COX-2) in cervicovaginal and endometrial tissue</measure>
    <time_frame>Baseline, IVR Day ~16-18</time_frame>
    <description>Markers of mucosal alteration and inflammation (e.g., expression of COX-2) in cervicovaginal and endometrial tissue</description>
  </other_outcome>
  <other_outcome>
    <measure>Microbial growth on swabs obtained from returned IVRs and microbial levels in returned IVRs</measure>
    <time_frame>IVR Day ~16-18 (post-removal)</time_frame>
    <description>Microbial growth on swabs obtained from returned IVRs and microbial levels in returned IVRs</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of association of TFV levels between less-invasive swabs and the more invasive biopsies, and possibly between swabs and aspirates</measure>
    <time_frame>IVR Day 2, ~16-18; 24 hours post-IVR removal</time_frame>
    <description>Level of association of TFV levels between less-invasive swabs and the more invasive biopsies, and possibly between swabs and aspirates</description>
  </other_outcome>
  <other_outcome>
    <measure>Characterization of returned IVRs for physicochemical properties and potential chemical and/or biological measures of adherence</measure>
    <time_frame>IVR Day ~16-18 (post-removal)</time_frame>
    <description>Characterization of returned IVRs for physicochemical properties and potential chemical and/or biological measures of adherence</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>HIV</condition>
  <condition>Contraception</condition>
  <arm_group>
    <arm_group_label>TFV IVR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TFV IVR is an intravaginal ring 55.0 mm in diameter, consisting of single segment of polyurethane tubing with an outer diameter of 5.5 mm and filled with white TFV-containing paste. Used for one month, the IVR delivers 8-10 mg/day TFV.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TFV/LNG IVR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TFV/LNG IVR is an intravaginal ring 55.0 mm in diameter, consisting of two segments of polyurethane tubing with an outer diameter of 5.5 mm: a longer segment containing white TFV paste and a shorter one (20 mm) with a white LNG core. Used for one month, the IVR delivers 8-10 mg/day TFV and 20 μg/day LNG.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Intravaginal Ring</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravaginal ring 55.0 mm in diameter, consisting of two segments of polyurethane tubing with an outer diameter of 5.5 mm containing no active experimental ingredients. Used for one month.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TFV IVR</intervention_name>
    <arm_group_label>TFV IVR</arm_group_label>
    <arm_group_label>TFV/LNG IVR</arm_group_label>
    <other_name>Tenofovir Intravaginal Ring</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TFV/LNG IVR</intervention_name>
    <arm_group_label>TFV/LNG IVR</arm_group_label>
    <other_name>Tenofovir Levonorgestrel Intravaginal Ring</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo IVR</intervention_name>
    <arm_group_label>Placebo Intravaginal Ring</arm_group_label>
    <other_name>Placebo Intravaginal Ring</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-45 years, inclusive&#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 26-35 days by participant report&#xD;
&#xD;
          -  History of Pap smears and follow-up consistent with standard medical practice as&#xD;
             outlined in the study manual or willing to undergo a Pap smear&#xD;
&#xD;
          -  Protected from pregnancy by one of the following: 1) Sterilization of either partner.&#xD;
             Note: Women protected from pregnancy by sterilization of either partner must abstain&#xD;
             from vaginal intercourse from 48 hours prior to Visit 3 until the sixth day after the&#xD;
             last study visit; or 2) Willing to abstain from vaginal intercourse from Visit 1 until&#xD;
             the sixth day after the last study visit.&#xD;
&#xD;
          -  Willing to abstain from any other vaginal activity and the use of vaginal product&#xD;
             other than the study product including tampons, spermicides, lubricants, and douches&#xD;
             starting 48 hours before Visit 3 until the sixth day after the last study visit&#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;
          -  P4 ≥3 ng/ml&#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 3 months (oral, transdermal,&#xD;
             transvaginal, implant, or hormonal intrauterine contraceptive device)&#xD;
&#xD;
          -  Injection of Depo-Provera in the last 10 months&#xD;
&#xD;
          -  Use of copper intrauterine device (IUD) after Visit 1&#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: TFV 1% gel, topical anesthetic, or&#xD;
             allergy to both silver nitrate and Monsel's solution.&#xD;
&#xD;
          -  Contraindication to LNG&#xD;
&#xD;
          -  In the last six months, diagnosed with or treated for any sexually transmitted&#xD;
             infection (STI) or pelvic inflammatory disease. Note: Women with a history of genital&#xD;
             herpes or condylomata who have been asymptomatic for at least six months may be&#xD;
             considered for eligibility.&#xD;
&#xD;
          -  Nugent score greater than or equal to 7 or symptomatic bacterial vaginosis (BV) as&#xD;
             defined by Amsel's criteria&#xD;
&#xD;
          -  Positive test for Trichomonas vaginalis, Neisseria gonorrhea (GC), Chlamydia&#xD;
             trachomatis (CT), HIV, or 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 2 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, or clinically significant laboratory&#xD;
             abnormality as determined by the clinician&#xD;
&#xD;
          -  Systemic use in the last two weeks or anticipated use during the study of any of the&#xD;
             following: corticosteroids, antibiotics, anticoagulants or other drugs known to&#xD;
             prolong bleeding and/or clotting, 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>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jill Schwartz, MD</last_name>
    <role>Study Chair</role>
    <affiliation>CONRAD</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Chris Mauck, MD</last_name>
    <role>Study Director</role>
    <affiliation>CONRAD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Eastern Virginia Medical School</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Profamilia</name>
      <address>
        <city>Santo Domingo</city>
        <country>Dominican Republic</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Dominican Republic</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>January 8, 2016</last_update_submitted>
  <last_update_submitted_qc>January 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 11, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>LNG</keyword>
  <keyword>IVR</keyword>
  <keyword>Contraception</keyword>
  <keyword>Prevention</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Levonorgestrel</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/NCT02235662
org study id: A13-128
nct id: NCT02235662
lead sponsor: 
has dmc: No
The purpose of the study is to evaluate the safety of the TFV/LNG intravaginal ring (IVR),
      TFV-only IVR, and placebo IVR, evaluate pharmacokinetics (PK) of TFV and LNG, evaluate
      pharmacodynamic (PD) surrogates of contraceptive efficacy of LNG, and to evaluate
      acceptability of the IVRs.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of treatment-emergent adverse events
time frame: IVR Day 1, 2, ~8, ~16-18; 24 hours and 1-2 weeks post-IVR insertion and 1-2 weeks after IVR removal
description: Number of treatment-emergent adverse events
measure: Systemic laboratory tests
time frame: Baseline and IVR Day ~16-18
description: Changes in Systemic laboratory tests
measure: Cervicovaginal ulcerations, abrasions, edema, and other findings
time frame: Baseline, IVR Day 2, ~8 and ~16-18
description: Development of cervicovaginal ulcerations, abrasions, edema, and other findings as assessed by naked eye and colposcopic visualization of the cervicovaginal epithelium
measure: Soluble markers of innate mucosal immunity and inflammatory response in cervicovaginal lavage (CVL) fluid
time frame: Baseline and IVR Day ~16-18
description: Changes in soluble markers of innate mucosal immunity and inflammatory response in CVL fluid
measure: HIV-1 target immune cell phenotype and HIV-1 activation/proliferation marker in cervicovaginal tissue (biopsy)
time frame: Baseline and IVR Day ~16-18
description: Changes in HIV-1 target immune cell phenotype and HIV-1 activation/proliferation marker in cervicovaginal tissue (biopsy)
measure: Microflora (semi-quantitative vaginal culture and/or unculturable bacteria)
time frame: Baseline and IVR Day ~16-18
description: Changes microflora (semi-quantitative vaginal culture and/or unculturable bacteria)
measure: Vaginal pH
time frame: Baseline and IVR Day ~16-18
description: Changes in vaginal pH
measure: Nugent Score
time frame: Baseline and IVR Day ~16-18
description: Changes in Nugent Score
measure: TFV concentrations in plasma
time frame: Baseline; 1, 2, 4 and 8 hrs post-IVR insertion; IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal
description: TFV concentrations in plasma
measure: TFV concentrations in cervicovaginal fluid (aspirate and swab)
time frame: 1, 2, 4 or 8 hours post-IVR insertion (randomized time point); IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal
description: TFV concentrations in cervicovaginal fluid (aspirate and swab)
measure: TFV concentrations in genital tissue (biopsy)
time frame: IVR Day 2, ~16-18; 24 or 72 hours post-IVR removal (randomized time point)
description: TFV concentrations in genital tissue (biopsy)
measure: Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs)
time frame: IVR Day ~16-18
description: TFV-DP concentrations in PBMCs
measure: TFV-DP concentrations in genital tissue (biopsy)
time frame: IVR Day 2, ~16-18; 24 or 72 hours post-IVR removal (randomized time point)
description: TFV-DP concentrations in genital tissue (biopsy)
measure: LNG concentration in blood (including SHBG)
time frame: Baseline; 1, 2, 4 and 8 hrs post-IVR insertion; IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal
description: LNG concentration in blood (including SHBG)
measure: LNG concentration in vaginal secretions (swabs)
time frame: Baseline; IVR Day~8
description: LNG concentration in vaginal secretions (swabs)
measure: LNG concentration in cervical mucus
time frame: IVR Day ~8, ~16-18; 24 hours post-IVR removal
description: LNG concentration in cervical mucus
measure: Weight of returned IVRs
time frame: IVR Day ~16-18 (post-removal)
description: Weight of returned IVRs
measure: Amount of drug remaining in returned IVRs
time frame: IVR Day ~16-18 (post-removal)
description: Amount of drug remaining in returned IVRs
measure: Cervical mucus assessment and sperm migration on the Simplified Slide test
time frame: IVR Day ~8
description: Surrogates of contraceptive efficacy - Cervical mucus assessment
measure: Ovulation by P4
time frame: IVR Day ~16-18
description: Surrogates of contraceptive efficacy - Ovulation by P4
measure: Follicular development by serum estradiol concentration
time frame: IVR Day ~8, ~16-18
description: Surrogates of contraceptive efficacy - Follicular development by serum estradiol concentration
measure: Acceptability of IVR
time frame: IVR Day ~16-18 (post-removal)
description: Acceptability of IVR as measured by a composite of the following factors: Discontinuations, Expulsions, Removals, Visible changes (such as discoloration) as documented on photographs of returned IVRs, Responses to key questions on acceptability questionnaire
measure: Pharmacodynamics
time frame: Baseline, IVR Day ~16-18
description: Pharmacodynamics - Anti-herpes simplex virus (HSV)-2 and Anti-HIV-1 activities in the CVL. Anti-HIV and anti-HSV activity as a percent of anti-HIV and anti-HSV activity before exposure to test product
measure: Pharmacodynamics
time frame: Baseline, IVR Day ~16-18
description: TFV anti-HIV efficacy in cervicovaginal tissues. Comparison of cervicovaginal tissue permissiveness to ex vivo infection with HIV-1 BaL between the control cycle and treatment cycle.
measure: Pharmacodynamic surrogates of LNG in endometrium
time frame: Baseline, IVR Day ~16-18
description: Findings on endometrial biopsy: Histology, Markers of endometrial function
measure: Endometrial thickness
time frame: Baseline, IVR Day ~16-18
description: Endometrial thickness as assessed by transvaginal ultrasound
measure: Cervicovaginal epithelial histology and epithelial integrity in cervicovaginal tissue (biopsy)
time frame: Baseline, IVR Day ~16-18
description: Cervicovaginal epithelial histology (thickness and number of cell layers) and epithelial integrity, as measured immuno-histochemistry (IHC) of epithelial junction proteins in cervicovaginal tissue (biopsy)
measure: Markers of mucosal alteration and inflammation (e.g., expression of COX-2) in cervicovaginal and endometrial tissue
time frame: Baseline, IVR Day ~16-18
description: Markers of mucosal alteration and inflammation (e.g., expression of COX-2) in cervicovaginal and endometrial tissue
measure: Microbial growth on swabs obtained from returned IVRs and microbial levels in returned IVRs
time frame: IVR Day ~16-18 (post-removal)
description: Microbial growth on swabs obtained from returned IVRs and microbial levels in returned IVRs
measure: Level of association of TFV levels between less-invasive swabs and the more invasive biopsies, and possibly between swabs and aspirates
time frame: IVR Day 2, ~16-18; 24 hours post-IVR removal
description: Level of association of TFV levels between less-invasive swabs and the more invasive biopsies, and possibly between swabs and aspirates
measure: Characterization of returned IVRs for physicochemical properties and potential chemical and/or biological measures of adherence
time frame: IVR Day ~16-18 (post-removal)
description: Characterization of returned IVRs for physicochemical properties and potential chemical and/or biological measures of adherence
arm group label: TFV IVR
arm group type: Experimental
description: TFV IVR is an intravaginal ring 55.0 mm in diameter, consisting of single segment of polyurethane tubing with an outer diameter of 5.5 mm and filled with white TFV-containing paste. Used for one month, the IVR delivers 8-10 mg/day TFV.
arm group label: TFV/LNG IVR
arm group type: Experimental
description: TFV/LNG IVR is an intravaginal ring 55.0 mm in diameter, consisting of two segments of polyurethane tubing with an outer diameter of 5.5 mm: a longer segment containing white TFV paste and a shorter one (20 mm) with a white LNG core. Used for one month, the IVR delivers 8-10 mg/day TFV and 20 μg/day LNG.
arm group label: Placebo Intravaginal Ring
arm group type: Placebo Comparator
description: Intravaginal ring 55.0 mm in diameter, consisting of two segments of polyurethane tubing with an outer diameter of 5.5 mm containing no active experimental ingredients. Used for one month.
intervention type: Drug
intervention name: TFV IVR
arm group label: TFV IVR
arm group label: TFV/LNG IVR
other name: Tenofovir Intravaginal Ring
intervention type: Drug
intervention name: TFV/LNG IVR
arm group label: TFV/LNG IVR
other name: Tenofovir Levonorgestrel Intravaginal Ring
intervention type: Other
intervention name: Placebo IVR
arm group label: Placebo Intravaginal Ring
other name: Placebo Intravaginal Ring
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jill Schwartz, MD
role: Study Chair
affiliation: CONRAD
last name: Chris Mauck, MD
role: Study Director
affiliation: CONRAD
facility: 
facility: 
country: Dominican Republic
country: United States
responsible party type: Sponsor
mesh term: Tenofovir
mesh term: Levonorgestrel