<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/NCT03239483</url>
  </required_header>
  <id_info>
    <org_study_id>MTN-026</org_study_id>
    <secondary_id>12021</secondary_id>
    <nct_id>NCT03239483</nct_id>
  </id_info>
  <brief_title>Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults</brief_title>
  <official_title>A Randomized, Double Blind, Placebo-Controlled, Phase 1 Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of dapivirine&#xD;
      gel (0.05%) administered rectally to HIV-1 seronegative adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate the safety and pharmacokinetics (PK) of dapivirine gel (0.05%)&#xD;
      administered rectally to HIV-1 seronegative adults.&#xD;
&#xD;
      Participants will be randomized to receive a single dose of either rectally administered&#xD;
      dapivirine gel (0.05%) or placebo gel at study entry (Day 0). Following a minimum 2-week&#xD;
      washout period, participants or study staff will administer daily rectal doses of the&#xD;
      assigned gel for 7 consecutive days under direct observation in the clinic.&#xD;
&#xD;
      Participants will be in the study for approximately 40 days, and they will attend 16 study&#xD;
      visits. Study visits may include behavioral assessments, physical examinations, blood and&#xD;
      urine collection, and pelvic and anorectal sample collection. Some visits will include&#xD;
      intensive PK sampling. Study staff will contact participants 1 week after Visit 16 for&#xD;
      follow-up safety monitoring.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 26, 2017</start_date>
  <completion_date type="Actual">September 20, 2018</completion_date>
  <primary_completion_date type="Actual">September 20, 2018</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of Grade 2 or Higher Adverse Events (AEs)</measure>
    <time_frame>Measured after the participant has started study product until the participant's study termination at approximately Day 40</time_frame>
    <description>As defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital [Dated November 2007], Male Genital [Dated November 2007] and Rectal [Clarification Dated May 2012] Grading Tables for Use in Microbicide Studies)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of Dapivirine Concentrations in Plasma</measure>
    <time_frame>Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, before last dose and 1,2, 24,48, and 72 hours after last dose.</time_frame>
    <description>As assessed by pharmacokinetic sampling and analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of Dapivirine Concentrations in Rectal Fluid</measure>
    <time_frame>Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, and 1,2, 24,48, and 72 hours after last dose.</time_frame>
    <description>As assessed by pharmacokinetic rectal fluid sampling and analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates</measure>
    <time_frame>Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose and 1,2, 24,48, and 72 hours after last dose.</time_frame>
    <description>As assessed by pharmacokinetic rectal mucosal tissue homogenates sampling and analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Half-life of Dapivirine Concentrations in Plasma</measure>
    <time_frame>From samples collected 24 hours after first dose to 72 hours after last daily dose</time_frame>
    <description>The terminal half-life of dapivirine in plasma samples was estimated by fitting a linear regression on the log-transformed concentrations from the 24, 48 and 72 hour time-points after the single and multiple doses.Each regression model includes an adjustment for the difference in concentration after multiple dosing. For each participant, Beta was calculated as the negative of the slope of their repression and half-life was log(2)/Beta. Due to the large number of concentrations below the limit of quantification after the single dose, the estimateion of Beta and half-life relied only on concentration after the multiple dosing for most of the participants.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acceptability: Ease of Use</measure>
    <time_frame>after completing the study (study day 40)</time_frame>
    <description>The number of participants who responded by questionnaire that the study product was easy or very easy to use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability: Comfort</measure>
    <time_frame>after completing the study (study day 40)</time_frame>
    <description>The number of participants who responded on a questionnaire that the study product was comfortable or very comfortable.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Dapivirine gel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo gel</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapivirine gel</intervention_name>
    <description>Dapivirine gel (0.05%); administered rectally</description>
    <arm_group_label>Dapivirine gel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo gel</intervention_name>
    <description>Universal HEC placebo gel; administered rectally</description>
    <arm_group_label>Placebo gel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age of 18 - 45 years (inclusive) at Screening, verified per site standard operating&#xD;
             procedure (SOP)&#xD;
&#xD;
          -  Able and willing to provide written informed consent&#xD;
&#xD;
          -  HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix&#xD;
             II of the protocol and willing to receive HIV test results&#xD;
&#xD;
          -  Able and willing to provide adequate locator information, as defined in site SOP&#xD;
&#xD;
          -  Available to return for all study visits and willing to comply with study&#xD;
             participation requirements&#xD;
&#xD;
          -  In general good health at Screening and Enrollment, as determined by the site&#xD;
             Investigator of Record (IoR) or designee&#xD;
&#xD;
          -  Per participant report, a history of consensual receptive anal intercourse (RAI) at&#xD;
             least once in the past calendar year&#xD;
&#xD;
          -  Willing to not take part in other research studies involving drugs, medical devices,&#xD;
             genital or rectal products, or vaccines for the duration of study participation,&#xD;
             including the time between Screening and Enrollment&#xD;
&#xD;
          -  Willing to be sexually abstinent for 72 hours prior to each study visit, during the&#xD;
             study product use periods and for 72 hours after biopsy collection. Note: See Criteria&#xD;
             12 and 13 for additional restrictions for female participants&#xD;
&#xD;
          -  Willing to abstain from inserting any non-study products into the rectum for 72 hours&#xD;
             prior to each study visit and during the study product use periods. Note: See Criteria&#xD;
             12 and 13 for additional restrictions for female participants&#xD;
&#xD;
        Females must also meet the following additional inclusion criteria to be eligible for study&#xD;
        inclusion:&#xD;
&#xD;
          -  Women over the age of 21 (inclusive) must have documentation of a satisfactory Pap&#xD;
             within the past 3 years prior to Enrollment consistent with Grade 0 according to the&#xD;
             Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (dated November&#xD;
             2007) to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected&#xD;
             Version 2.1, July 2017, or satisfactory evaluation with no treatment required of Grade&#xD;
             1 or higher Pap result&#xD;
&#xD;
          -  Willing to be sexually abstinent for 72 hours prior to each study visit and during the&#xD;
             study product use periods and for 7 days after biopsy collection&#xD;
&#xD;
          -  Willing to abstain from inserting any non-study products into the vagina for 72 hours&#xD;
             prior to each study visit, during the study product use periods and for 7 days after&#xD;
             biopsy collection&#xD;
&#xD;
          -  Willing to use an effective method of contraception for at least 30 days (inclusive)&#xD;
             prior to Enrollment and intending to continue use of an effective method for the&#xD;
             duration of study participation; effective methods include: hormonal methods (except&#xD;
             contraceptive ring), intrauterine device (IUD), sterilization (of participant and/or&#xD;
             partner, as defined in site SOPs), or sexually abstinent for 90 days prior to&#xD;
             Screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  At Screening:&#xD;
&#xD;
               -  Hemoglobin Grade 1 or higher*&#xD;
&#xD;
               -  Platelet count Grade 1 or higher*&#xD;
&#xD;
               -  White blood count Grade 2 or higher*&#xD;
&#xD;
               -  Serum creatinine greater than 1.3× the site laboratory upper limit of normal&#xD;
                  (ULN)&#xD;
&#xD;
               -  International normalized ratio (INR) greater than 1.5× the site laboratory ULN&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher*&#xD;
&#xD;
               -  Positive for hepatitis C antibody&#xD;
&#xD;
               -  Positive for hepatitis B surface antigen&#xD;
&#xD;
               -  History of inflammatory bowel disease by participant report&#xD;
&#xD;
               -  *As per the Division of AIDS Table for Grading the Severity of Adult and&#xD;
                  Pediatric Adverse Events Corrected Version 2.1, July 2017&#xD;
&#xD;
               -  Note: Otherwise eligible participants with an exclusionary test result (other&#xD;
                  than HIV, HBV or HCV) can be re-tested during the screening process. If a&#xD;
                  participant is re-tested and a non-exclusionary result is documented within 45&#xD;
                  days of providing informed consent for screening, the participant may be&#xD;
                  enrolled.&#xD;
&#xD;
          -  Anticipated use of and/or unwillingness to abstain from the following medications&#xD;
             during study participation:&#xD;
&#xD;
               -  Heparin, including Lovenox®&#xD;
&#xD;
               -  Warfarin&#xD;
&#xD;
               -  Plavix® (clopidogrel bisulfate)&#xD;
&#xD;
               -  Aspirin (greater than 81 mg)&#xD;
&#xD;
               -  Non-steroidal anti-inflammatory drugs (NSAIDS)&#xD;
&#xD;
               -  Any other drugs that are associated with increased likelihood of bleeding&#xD;
&#xD;
               -  CYP3A inducer(s) and/or inhibitor(s) as specified in the MTN-026 Study-Specific&#xD;
                  Procedures (SSP) Manual&#xD;
&#xD;
               -  Hormone-replacement therapy in tablet, injectable or gel form&#xD;
&#xD;
          -  Known adverse reaction to any of the components of the study products&#xD;
&#xD;
          -  Use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 6 months&#xD;
             prior to Enrollment&#xD;
&#xD;
          -  Use of pre-exposure prophylaxis (PrEP) for HIV prevention within the 6 months prior to&#xD;
             Enrollment, and/or anticipated use during trial participation&#xD;
&#xD;
          -  Use of systemic immunomodulatory medications within the 6 months prior to Enrollment,&#xD;
             and/or anticipated use during trial participation&#xD;
&#xD;
          -  RAI without a condom and/or penile-vaginal intercourse with a partner who is known to&#xD;
             be HIV-positive in the past 6 months&#xD;
&#xD;
          -  Non-therapeutic injection drug use in the 12 months prior to Screening and Enrollment&#xD;
&#xD;
          -  Participation in research studies involving drugs, medical devices, genital or rectal&#xD;
             products, or vaccines within 45 days of the Enrollment Visit&#xD;
&#xD;
          -  At Screening, participant report of treatment for an anogenital STI within the past 3&#xD;
             months&#xD;
&#xD;
          -  At Screening, participant-reported symptoms and/or clinical or laboratory diagnosis of&#xD;
             active anorectal or reproductive tract infection requiring treatment per current World&#xD;
             Health Organization (WHO) guidelines (http://www.who.int/hiv/pub/sti/pub6/en/) or&#xD;
             symptomatic urinary tract infection (UTI). Infections requiring treatment include&#xD;
             symptomatic Neisseria gonorrhea (GC), Chlamydia trachomatis (CT) infection, syphilis,&#xD;
             active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic&#xD;
             genital warts, cervicitis, chancroid, pelvic inflammatory disease (PID), bacterial&#xD;
             vaginosis (BV), symptomatic vaginal candidiasis, other vaginitis, trichomoniasis.&#xD;
             Note: Otherwise eligible participants with an exclusionary UTI, BV and/or candida&#xD;
             finding may be re-tested during the screening process.&#xD;
&#xD;
          -  At Enrollment, active anorectal or reproductive tract infection requiring treatment&#xD;
             per current WHO guidelines (http://www.who.int/hiv/pub/sti/pub6/en/) or symptomatic&#xD;
             urinary tract infection (UTI). Infections requiring treatment include symptomatic GC,&#xD;
             CT, syphilis, active HSV lesions, anogenital sores or ulcers, symptomatic genital&#xD;
             warts, bacterial vaginosis, symptomatic vaginal candidiasis, other vaginitis,&#xD;
             trichomoniasis, chancroid, cervicitis and PID. Note: HSV-1 or HSV-2 seropositive&#xD;
             diagnosis with no active lesions is permitted since treatment is not required&#xD;
&#xD;
          -  Has any other condition that, in the opinion of the IoR/designee, would preclude&#xD;
             informed consent, make study participation unsafe, complicate interpretation of study&#xD;
             outcome data, or otherwise interfere with achieving study objectives.&#xD;
&#xD;
        Females who meet any of the following additional criteria will be excluded from the study:&#xD;
&#xD;
          -  Pregnant or breastfeeding at either Screening or Enrollment or intends to become&#xD;
             pregnant or start breastfeeding during study participation. Note: A documented&#xD;
             negative pregnancy test performed by study staff is required for inclusion; however, a&#xD;
             self-reported pregnancy is adequate for exclusion from screening/enrollment into the&#xD;
             study.&#xD;
&#xD;
          -  Last pregnancy outcome 90 days or less prior to Screening&#xD;
&#xD;
          -  Has had a hysterectomy&#xD;
&#xD;
          -  At Enrollment, has a clinically apparent Grade 1 or higher pelvic exam finding&#xD;
             (observed by study clinician or designee) per the Female Genital Grading Table for Use&#xD;
             in Microbicide Studies [Addendum 1, Dated November 2007]. Note: Cervical friability&#xD;
             bleeding associated with speculum insertion and/or specimen collection judged to be&#xD;
             within the range of normal according to the clinical judgment of the IoR/designee is&#xD;
             considered expected non-menstrual bleeding and is not exclusionary.&#xD;
      </textblock>
    </criteria>
    <gender>All</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>Ross D. Cranston, MD, FRCP</last_name>
    <role>Study Chair</role>
    <affiliation>Fundació Lluita Contra la Sida, Hospital Universitari Germans Trias I Pujol</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alabama CRS</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh CRS</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Silom Community Clinic CRS</name>
      <address>
        <city>Nonthaburi</city>
        <state>Bangkok</state>
        <zip>11000</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <results_first_submitted>September 19, 2019</results_first_submitted>
  <results_first_submitted_qc>October 18, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 7, 2019</results_first_posted>
  <last_update_submitted>October 15, 2021</last_update_submitted>
  <last_update_submitted_qc>October 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dapivirine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03239483/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 3, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03239483/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dapivirine Gel</title>
          <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
        </group>
        <group group_id="P2">
          <title>Placebo Gel</title>
          <description>Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.&#xD;
Placebo gel: Universal HEC placebo gel; administered rectally</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dapivirine Gel</title>
          <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
        </group>
        <group group_id="B2">
          <title>Placebo Gel</title>
          <description>Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.&#xD;
Placebo gel: Universal HEC placebo gel; administered rectally</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="28"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26" lower_limit="18" upper_limit="42"/>
                    <measurement group_id="B2" value="35" lower_limit="21" upper_limit="40"/>
                    <measurement group_id="B3" value="33" lower_limit="18" upper_limit="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thailand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Frequency of Grade 2 or Higher Adverse Events (AEs)</title>
        <description>As defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital [Dated November 2007], Male Genital [Dated November 2007] and Rectal [Clarification Dated May 2012] Grading Tables for Use in Microbicide Studies)</description>
        <time_frame>Measured after the participant has started study product until the participant's study termination at approximately Day 40</time_frame>
        <population>enrolled participants receiving at least one dose of study product</population>
        <group_list>
          <group group_id="O1">
            <title>Dapivirine Gel</title>
            <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
          </group>
          <group group_id="O2">
            <title>Placebo Gel</title>
            <description>Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.&#xD;
Placebo gel: Universal HEC placebo gel; administered rectally</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Grade 2 or Higher Adverse Events (AEs)</title>
          <description>As defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital [Dated November 2007], Male Genital [Dated November 2007] and Rectal [Clarification Dated May 2012] Grading Tables for Use in Microbicide Studies)</description>
          <population>enrolled participants receiving at least one dose of study product</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>two-sided Fisher's Exact Test</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.072</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Measurement of Dapivirine Concentrations in Plasma</title>
        <description>As assessed by pharmacokinetic sampling and analysis</description>
        <time_frame>Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, before last dose and 1,2, 24,48, and 72 hours after last dose.</time_frame>
        <population>enrolled participants on the Dapivirine arm who received at least one dose of study product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 20 pg/mL) since only numeric values are allowed. The value would be somewhere between the LLOQ and 0.</population>
        <group_list>
          <group group_id="O1">
            <title>Dapivirine Gel</title>
            <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
          </group>
        </group_list>
        <measure>
          <title>Measurement of Dapivirine Concentrations in Plasma</title>
          <description>As assessed by pharmacokinetic sampling and analysis</description>
          <population>enrolled participants on the Dapivirine arm who received at least one dose of study product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 20 pg/mL) since only numeric values are allowed. The value would be somewhere between the LLOQ and 0.</population>
          <units>pg/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 to 60 minutes after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.5" lower_limit="0" upper_limit="54.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="326" lower_limit="153" upper_limit="481"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.1" lower_limit="0" upper_limit="56.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours after first daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.9" lower_limit="43.1" upper_limit="111.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Before last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="167" lower_limit="136" upper_limit="219"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 to 60 minutes after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="290.5" lower_limit="147.0" upper_limit="506.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="403" lower_limit="330" upper_limit="493"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119.0" lower_limit="86.4" upper_limit="172.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113" lower_limit="69" upper_limit="132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.3" lower_limit="47.3" upper_limit="129.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Measurement of Dapivirine Concentrations in Rectal Fluid</title>
        <description>As assessed by pharmacokinetic rectal fluid sampling and analysis</description>
        <time_frame>Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, and 1,2, 24,48, and 72 hours after last dose.</time_frame>
        <population>enrolled participants on the Dapivirine arm who received at least one dose of product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 0.001 ng/mg) since only numeric values are allowed. The value would be somewhere between the lower limit of quantification and 0.</population>
        <group_list>
          <group group_id="O1">
            <title>Dapivirine Gel</title>
            <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
          </group>
        </group_list>
        <measure>
          <title>Measurement of Dapivirine Concentrations in Rectal Fluid</title>
          <description>As assessed by pharmacokinetic rectal fluid sampling and analysis</description>
          <population>enrolled participants on the Dapivirine arm who received at least one dose of product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 0.001 ng/mg) since only numeric values are allowed. The value would be somewhere between the lower limit of quantification and 0.</population>
          <units>ng/mg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 to 60 minutes after first application</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.1" lower_limit="16.1" upper_limit="43.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.765" lower_limit="6.055" upper_limit="141.500"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0.016"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.009" lower_limit="0" upper_limit="0.038"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours after first daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.180" lower_limit="0" upper_limit="1.910"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 to 60 minutes after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.7" lower_limit="44.9" upper_limit="258.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.65" lower_limit="4.95" upper_limit="278.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.007" lower_limit="0" upper_limit="0.096"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0.042"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0.013"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates</title>
        <description>As assessed by pharmacokinetic rectal mucosal tissue homogenates sampling and analysis</description>
        <time_frame>Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose and 1,2, 24,48, and 72 hours after last dose.</time_frame>
        <population>enrolled participants on the Dapivirine gel arm who received at least one dose of study product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 0.001 ng/mg) since only numeric values are allowed. The value would be somewhere between the LLOQ and 0.</population>
        <group_list>
          <group group_id="O1">
            <title>Dapivirine Gel</title>
            <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
          </group>
        </group_list>
        <measure>
          <title>Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates</title>
          <description>As assessed by pharmacokinetic rectal mucosal tissue homogenates sampling and analysis</description>
          <population>enrolled participants on the Dapivirine gel arm who received at least one dose of study product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 0.001 ng/mg) since only numeric values are allowed. The value would be somewhere between the LLOQ and 0.</population>
          <units>ng/mg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 to 60 minutes after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.256" lower_limit="0" upper_limit="0.666"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0.600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours after single dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 to 60 minutes after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0.151"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours after last daily dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Terminal Half-life of Dapivirine Concentrations in Plasma</title>
        <description>The terminal half-life of dapivirine in plasma samples was estimated by fitting a linear regression on the log-transformed concentrations from the 24, 48 and 72 hour time-points after the single and multiple doses.Each regression model includes an adjustment for the difference in concentration after multiple dosing. For each participant, Beta was calculated as the negative of the slope of their repression and half-life was log(2)/Beta. Due to the large number of concentrations below the limit of quantification after the single dose, the estimateion of Beta and half-life relied only on concentration after the multiple dosing for most of the participants.</description>
        <time_frame>From samples collected 24 hours after first dose to 72 hours after last daily dose</time_frame>
        <population>enrolled participants on the Dapivirine gel arm who received at least one dose of study product. One participant with a negative estimate for the elimination rate due to an increasing trend in their concentration after multiple dosing and one participant with no values above the limit of quantification were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>Dapivirine Gel</title>
            <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-life of Dapivirine Concentrations in Plasma</title>
          <description>The terminal half-life of dapivirine in plasma samples was estimated by fitting a linear regression on the log-transformed concentrations from the 24, 48 and 72 hour time-points after the single and multiple doses.Each regression model includes an adjustment for the difference in concentration after multiple dosing. For each participant, Beta was calculated as the negative of the slope of their repression and half-life was log(2)/Beta. Due to the large number of concentrations below the limit of quantification after the single dose, the estimateion of Beta and half-life relied only on concentration after the multiple dosing for most of the participants.</description>
          <population>enrolled participants on the Dapivirine gel arm who received at least one dose of study product. One participant with a negative estimate for the elimination rate due to an increasing trend in their concentration after multiple dosing and one participant with no values above the limit of quantification were excluded.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.6" lower_limit="35.3" upper_limit="86.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Acceptability: Ease of Use</title>
        <description>The number of participants who responded by questionnaire that the study product was easy or very easy to use.</description>
        <time_frame>after completing the study (study day 40)</time_frame>
        <population>All enrolled participants who completed the exit behavioral questionnaire.</population>
        <group_list>
          <group group_id="O1">
            <title>Dapivirine Gel</title>
            <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
          </group>
          <group group_id="O2">
            <title>Placebo Gel</title>
            <description>Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.&#xD;
Placebo gel: Universal HEC placebo gel; administered rectally</description>
          </group>
        </group_list>
        <measure>
          <title>Acceptability: Ease of Use</title>
          <description>The number of participants who responded by questionnaire that the study product was easy or very easy to use.</description>
          <population>All enrolled participants who completed the exit behavioral questionnaire.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.00</p_value>
            <p_value_desc>This is a calculated p-value. P-values of 1.0 are possible when using the Fisher Exact test method.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Acceptability: Comfort</title>
        <description>The number of participants who responded on a questionnaire that the study product was comfortable or very comfortable.</description>
        <time_frame>after completing the study (study day 40)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dapivirine Gel</title>
            <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
          </group>
          <group group_id="O2">
            <title>Placebo Gel</title>
            <description>Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.&#xD;
Placebo gel: Universal HEC placebo gel; administered rectally</description>
          </group>
        </group_list>
        <measure>
          <title>Acceptability: Comfort</title>
          <description>The number of participants who responded on a questionnaire that the study product was comfortable or very comfortable.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.591</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected through study completion (between 40 to 86 days).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Dapivirine Gel</title>
          <description>Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.&#xD;
Dapivirine gel: Dapivirine gel (0.05%); administered rectally</description>
        </group>
        <group group_id="E2">
          <title>Placebo Gel</title>
          <description>Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.&#xD;
Placebo gel: Universal HEC placebo gel; administered rectally</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anal pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Dyschezia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Joint dislocation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>procedural pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>blood pressure increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>coccydynia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Ross D. Cranston</name_or_title>
      <organization>Fundacio Lluita Contra la Sida, Hospital Universitari Germans Trias | Pujol</organization>
      <phone>34-934-657-897</phone>
      <email>rdcranston@outlook.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03239483
org study id: MTN-026
secondary id: 12021
nct id: NCT03239483
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of dapivirine
      gel (0.05%) administered rectally to HIV-1 seronegative adults.
This study will evaluate the safety and pharmacokinetics (PK) of dapivirine gel (0.05%)
      administered rectally to HIV-1 seronegative adults.

      Participants will be randomized to receive a single dose of either rectally administered
      dapivirine gel (0.05%) or placebo gel at study entry (Day 0). Following a minimum 2-week
      washout period, participants or study staff will administer daily rectal doses of the
      assigned gel for 7 consecutive days under direct observation in the clinic.

      Participants will be in the study for approximately 40 days, and they will attend 16 study
      visits. Study visits may include behavioral assessments, physical examinations, blood and
      urine collection, and pelvic and anorectal sample collection. Some visits will include
      intensive PK sampling. Study staff will contact participants 1 week after Visit 16 for
      follow-up safety monitoring.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Frequency of Grade 2 or Higher Adverse Events (AEs)
time frame: Measured after the participant has started study product until the participant's study termination at approximately Day 40
description: As defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital [Dated November 2007], Male Genital [Dated November 2007] and Rectal [Clarification Dated May 2012] Grading Tables for Use in Microbicide Studies)
measure: Measurement of Dapivirine Concentrations in Plasma
time frame: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, before last dose and 1,2, 24,48, and 72 hours after last dose.
description: As assessed by pharmacokinetic sampling and analysis
measure: Measurement of Dapivirine Concentrations in Rectal Fluid
time frame: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, and 1,2, 24,48, and 72 hours after last dose.
description: As assessed by pharmacokinetic rectal fluid sampling and analysis
measure: Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates
time frame: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose and 1,2, 24,48, and 72 hours after last dose.
description: As assessed by pharmacokinetic rectal mucosal tissue homogenates sampling and analysis
measure: Terminal Half-life of Dapivirine Concentrations in Plasma
time frame: From samples collected 24 hours after first dose to 72 hours after last daily dose
description: The terminal half-life of dapivirine in plasma samples was estimated by fitting a linear regression on the log-transformed concentrations from the 24, 48 and 72 hour time-points after the single and multiple doses.Each regression model includes an adjustment for the difference in concentration after multiple dosing. For each participant, Beta was calculated as the negative of the slope of their repression and half-life was log(2)/Beta. Due to the large number of concentrations below the limit of quantification after the single dose, the estimateion of Beta and half-life relied only on concentration after the multiple dosing for most of the participants.
measure: Acceptability: Ease of Use
time frame: after completing the study (study day 40)
description: The number of participants who responded by questionnaire that the study product was easy or very easy to use.
measure: Acceptability: Comfort
time frame: after completing the study (study day 40)
description: The number of participants who responded on a questionnaire that the study product was comfortable or very comfortable.
arm group label: Dapivirine gel
arm group type: Experimental
description: Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.
arm group label: Placebo gel
arm group type: Placebo Comparator
description: Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.
intervention type: Drug
intervention name: Dapivirine gel
description: Dapivirine gel (0.05%); administered rectally
arm group label: Dapivirine gel
intervention type: Drug
intervention name: Placebo gel
description: Universal HEC placebo gel; administered rectally
arm group label: Placebo gel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ross D. Cranston, MD, FRCP
role: Study Chair
affiliation: Fundació Lluita Contra la Sida, Hospital Universitari Germans Trias I Pujol
facility: 
facility: 
facility: 
country: Thailand
country: United States
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Dapivirine
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 