<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/NCT01687205</url>
  </required_header>
  <id_info>
    <org_study_id>MTN-011</org_study_id>
    <secondary_id>3UM1AI068633</secondary_id>
    <secondary_id>UM1AI068615</secondary_id>
    <secondary_id>11825</secondary_id>
    <nct_id>NCT01687205</nct_id>
  </id_info>
  <brief_title>Coital Pharmacokinetics/Pharmacodynamics (PK/PD) of Tenofovir Gel</brief_title>
  <official_title>Phase 1 Evaluation of the Impact of Coitus on Pharmacokinetics and Pharmacodynamics of Tenofovir 1% Gel Following Pericoital or Daily Gel Dosing</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CONRAD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>CONRAD</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study Objectives:&#xD;
&#xD;
        -  To assess the impact of coitus (and semen) on the pharmacokinetics of tenofovir 1% gel&#xD;
           in female genital tract secretions, vaginal and cervical tissue and rectal tract&#xD;
           secretions&#xD;
&#xD;
        -  To assess the impact of coitus (and semen) on pharmacodynamics of luminal drug by&#xD;
           measuring the anti-HIV-1 activity in CVL samples&#xD;
&#xD;
      Study Summary:&#xD;
&#xD;
      MTN-011 will enroll heterosexual monogamous, sexually active couples, in which both partners&#xD;
      are healthy and HIV-negative. The female participants must be between the ages of 21-46&#xD;
      (inclusive) and currently using effective non-barrier contraception. Male participants must&#xD;
      be 21 years of age or older. This Phase 1 expanded safety study will assess tenofovir PK in&#xD;
      the genital tract secretions (CVL), rectal (rectal sponge) and both intracellular and&#xD;
      extracellular tissue compartments (vaginal biopsy) in the absence of, or following coitus.&#xD;
      Pharmacodynamics (antiviral activity) will also be assessed in CVL. MTN-011 will study the&#xD;
      timing in which coitus might have the greatest impact on these variables, which is when gel&#xD;
      is applied shortly prior to coitus in the absence of a drug reservoir.&#xD;
&#xD;
      MTN-011 will examine PK/PD in response to a single dose of 1% tenofovir gel applied shortly&#xD;
      before sex and compare to PK/PD assessments following a single gel application without sex.&#xD;
      Additionally, data obtained from a visit in which participants do not dose with gel and do&#xD;
      not have sex will serve as an additional control for the pharmacodynamic (PD) studies of the&#xD;
      antiviral activity in CVL. If tenofovir retains its antiviral activity following sex, then&#xD;
      the anti-HIV activity in CVL collected at the visit in which female participants dose with&#xD;
      gel and have sex should be comparable to that of CVL collected at the visit in which females&#xD;
      dose with gel and then do not engage in intercourse and significantly greater than the&#xD;
      endogenous anti-HIV activity in CVL obtained at the visit in which participants do not dose&#xD;
      with gel but do have sex and the visit in which no gel is administered and sex does occur.&#xD;
      Data analysis performed after the completion of enrollment and follow-up procedures will&#xD;
      demonstrate if there is an impact of coitus and semen on PK/PD when a single 1% tenofovir&#xD;
      dose is applied shortly prior to sex.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of tenofovir 1% gel</measure>
    <time_frame>Visits 3b, 4b, 5b, 6b and 7b.</time_frame>
    <description>To assess the impact of coitus (and semen) on the pharmacokinetics of tenofovir 1% gel in female genital tract secretions, vaginal and cervical tissue and rectal tract secretions</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacodynamics of luminal drug</measure>
    <time_frame>Visits 2b, 3b, 4b, 5b, 6b and 7b.</time_frame>
    <description>To assess the impact of coitus (and semen) on pharmacodynamics of luminal drug by measuring the anti-HIV-1 activity in CVL samples</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acceptability</measure>
    <time_frame>Visit 7b.</time_frame>
    <description>To assess the acceptability of the MTN-011 trial to male and female participants</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Impact of coitus and/or tenofovir on the genital tract mucosal environment</measure>
    <time_frame>Visits 1, 2b, 3b, 4b, 5b, 6b and 7b.</time_frame>
    <description>To assess the impact of coitus and/or tenofovir on the genital tract musical environment</description>
  </other_outcome>
  <other_outcome>
    <measure>Semen biomarker</measure>
    <time_frame>Visits 1, 2b, 3b, 5b and 7b.</time_frame>
    <description>To determine whether a semen biomarker can be used to estimate the volume of ejaculate within CVL</description>
  </other_outcome>
  <other_outcome>
    <measure>Retained drug levels in the lumen</measure>
    <time_frame>Visits 1, 2b, 3b, 4b, 5b, 6b and 7b.</time_frame>
    <description>To assess whether sufficient drug is retained in the lumen in the absence of or following coitus to inhibit HSV-2 as an additional surrogate biomarker of pharmacodynamics</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Pharmacokinetics of 1% Tenofovir Gel Following Coitus</condition>
  <condition>Pharmacodynamics of 1% Tenofovir Gel Following Coitus</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single Dose/1 hour before and 1 hour after sex (BAT) Cohort</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Multiple Dose Cohort</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1% Tenofovir Gel</intervention_name>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Men and women must meet the following criteria to be eligible for inclusion in the study:&#xD;
&#xD;
          1. Able and willing to provide the following:&#xD;
&#xD;
               -  Written informed consent to be screened for and take part in the study&#xD;
&#xD;
               -  Adequate locator information, as defined in site SOPs&#xD;
&#xD;
          2. Per participant report, at low risk for HIV/STI. Low risk is defined as:&#xD;
&#xD;
               -  No sexually transmitted infections (STIs) in the 6 months prior to Screening&#xD;
&#xD;
               -  No non-therapeutic intravenous drug use in the 18 months prior to Screening&#xD;
&#xD;
               -  In a mutually monogamous relationship with a partner of the opposite sex for 6&#xD;
                  months prior to Screening and the intent to stay in this relationship for the&#xD;
                  next 4 months&#xD;
&#xD;
          3. At Screening and Enrollment, both partners independently report not using barrier&#xD;
             contraception and/or barrier protection as part of normal coital routine and report&#xD;
             the intent to continue said sexual practice for the duration of study participation&#xD;
&#xD;
          4. HIV-uninfected based upon testing performed by study staff at Screening (per protocol&#xD;
             algorithm)&#xD;
&#xD;
          5. Agrees not to participate in other research studies involving drugs, medical devices,&#xD;
             or genital and rectal products, or large blood draw studies during study participation&#xD;
&#xD;
          6. Women must also meet the following criteria:&#xD;
&#xD;
               -  Age 21 through 46 years (inclusive) at Screening, verified per site SOPs&#xD;
&#xD;
               -  Pap result in the 12 calendar months prior to Screening consistent with Grade 0&#xD;
                  according to the Female Genital Grading Table for Use in Microbicide Studies&#xD;
                  Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events,&#xD;
                  Version 1.0, December 2004 (Clarification dated August 2009), or satisfactory&#xD;
                  evaluation with no treatment required of non-Grade 0 Pap result per American&#xD;
                  Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in the 12&#xD;
                  calendar months prior to the Screening Visit&#xD;
&#xD;
             Note: Women with a documented normal result within the 12 months prior to screening&#xD;
             need not have a Pap smear during the screening period. Women with abnormal Pap smears&#xD;
             can be enrolled upon completion of the initial phase of evaluation if no current&#xD;
             treatment is indicated (based on local standard of care for management of abnormal&#xD;
             cervical cytology). Need for a repeat Pap within 6 months does not preclude enrollment&#xD;
             prior to that result becoming available.&#xD;
&#xD;
               -  Must be currently using effective non-barrier contraception, other than a&#xD;
                  contraceptive vaginal ring, for at least three months prior to Screening (i.e.,&#xD;
                  oral contraceptive, patch, injectable hormones, subdermal implants, intrauterine&#xD;
                  device, female or male sterilization) and intending to use this method for the&#xD;
                  course of the study&#xD;
&#xD;
               -  Per participant report, regular menstrual cycles with at least 21 days between&#xD;
                  menses (does not apply to participants who report using a progestin-only method&#xD;
                  of contraception at screening, e.g., Depo-Provera)&#xD;
&#xD;
             Note: This criterion is not applicable to participants using continuous combination&#xD;
             oral contraceptive pills, as the absence of regular menstrual cycles is an expected,&#xD;
             normal consequence in this context.&#xD;
&#xD;
               -  Anatomy sufficient for performing pelvic examinations and for collecting vaginal&#xD;
                  and cervical specimens&#xD;
&#xD;
               -  Female participants must also agree to abstain from intercourse (oral, anal, or&#xD;
                  penile-vaginal) and other vaginal practices (e.g., masturbation, douching, tampon&#xD;
                  use, application of lubricants/spermicides or other related practices) 72 hours&#xD;
                  prior to each follow-up visit.&#xD;
&#xD;
          7. Men must also meet the following criteria:&#xD;
&#xD;
               -  Age 21 or older at Screening, verified per site SOPs&#xD;
&#xD;
               -  Agree to abstain from intercourse (oral, anal, or penile-vaginal) and other&#xD;
                  penile practices (e.g., masturbation, application of lubricants/spermicides or&#xD;
                  other related practices) 72 hours prior to each follow-up visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Men and women who meet any of the following criteria will be excluded from the study.&#xD;
&#xD;
          1. Participant report of any of the following:&#xD;
&#xD;
               -  Known allergy to the study product (ever)&#xD;
&#xD;
               -  Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to&#xD;
                  Screening&#xD;
&#xD;
               -  Participation in any other research study involving drugs, medical devices, or&#xD;
                  genital products 30 days or less prior to Enrollment&#xD;
&#xD;
               -  Plans to relocate away from the study site in the next 4 months&#xD;
&#xD;
               -  History of domestic violence with current partner (ever)&#xD;
&#xD;
               -  Systemic or topical antimicrobials within the last 7 days prior to Enrollment&#xD;
&#xD;
               -  Currently using or planning to use pharmacologic immune modulator(s)&#xD;
&#xD;
          2. At Screening or Enrollment, symptomatic urinary tract infection (UTI)&#xD;
&#xD;
             Note: Otherwise eligible participants diagnosed with UTI during screening are offered&#xD;
             treatment and may be enrolled after completing treatment and all symptoms have&#xD;
             resolved as long as treatment is completed and all symptoms have resolved within 30&#xD;
             days of obtaining informed consent for Screening/Enrollment.&#xD;
&#xD;
          3. At Screening, has a positive hepatitis B surface antigen (HBsAg) test result&#xD;
&#xD;
          4. At Screening or Enrollment, has an STI or reproductive tract infection (RTI) requiring&#xD;
             treatment per current Centers for Disease Control (CDC) guidelines&#xD;
&#xD;
          5. Genital signs and/or symptoms of Grade 2 or higher&#xD;
&#xD;
             Note: For female participants, cervical bleeding associated with speculum insertion&#xD;
             and/or specimen collection judged to be within the range of normal according to the&#xD;
             clinical judgment of the IoR/designee is considered expected non-menstrual bleeding&#xD;
             and is not exclusionary.&#xD;
&#xD;
             Note: Otherwise eligible participants with exclusionary genital findings may be&#xD;
             enrolled after the findings have improved to a non-exclusionary severity grading or&#xD;
             resolved as long as treatment is completed and all symptoms have resolved within 30&#xD;
             days of obtaining informed consent for Screening/Enrollment.&#xD;
&#xD;
          6. Has any other condition that, in the opinion of the Investigator of Record&#xD;
             (IoR)/designee, would preclude informed consent, make study participation unsafe,&#xD;
             complicate interpretation of study outcome data, or otherwise interfere with achieving&#xD;
             the study objectives&#xD;
&#xD;
          7. Women who meet any of the following criteria will be excluded from the study:&#xD;
&#xD;
               -  Participant report (or clinical finding) of the following:&#xD;
&#xD;
                    -  Last pregnancy outcome 90 days or less prior to Enrollment&#xD;
&#xD;
                    -  Currently pregnant&#xD;
&#xD;
             Note: Self-reported pregnancy is adequate for exclusion from the study. A documented&#xD;
             negative pregnancy test performed by study staff is required for inclusion.&#xD;
&#xD;
               -  Currently breastfeeding&#xD;
&#xD;
               -  Intends to become pregnant in the next 4 months&#xD;
&#xD;
               -  Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage)&#xD;
                  within the prior 30 days to Enrollment&#xD;
&#xD;
             Note: This does not include biopsy for the evaluation of an abnormal pap result or&#xD;
             endometrial biopsy that occurred more than 7 days prior to Enrollment.&#xD;
&#xD;
               -  Any of the following laboratory abnormalities at Screening:&#xD;
&#xD;
                    -  Hemoglobin less than 10.0 g/dl&#xD;
&#xD;
                    -  Platelet count less than 100,000/mm3&#xD;
&#xD;
             Note: Otherwise eligible participants with an exclusionary test may be re-tested&#xD;
             during the screening process&#xD;
&#xD;
               -  Use of a vaginal douche or other intravaginal products (excluding tampon use) in&#xD;
                  the 30 days prior to Enrollment&#xD;
&#xD;
               -  Currently menopausal or perimenopausal&#xD;
&#xD;
          8. Men who meet any of the following criteria will be excluded from the study:&#xD;
&#xD;
               -  Participant report of penile procedures (e.g. biopsy, circumcision) within 42&#xD;
                  days prior to Enrollment&#xD;
&#xD;
               -  For uncircumcised men, per participant report, treatment of candidal&#xD;
                  balanoposthitis/ balanitis within 30 days prior to Enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>46 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Betsy Herold, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Albert Einstein College of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Beatrice A. Chen, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert A. Salata, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Case Western Reserve University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Case Western Reserve University</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magee-Womens Hospital of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Herold BC, Chen BA, Salata RA, Marzinke MA, Kelly CW, Dezzutti CS, McGowan I, Galaska B, Levy L, Piper JM, Hillier S, Hendrix CW. Impact of Sex on the Pharmacokinetics and Pharmacodynamics of 1% Tenofovir Gel. Clin Infect Dis. 2016 Feb 1;62(3):375-382. doi: 10.1093/cid/civ913. Epub 2015 Oct 27.</citation>
    <PMID>26508513</PMID>
  </results_reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>June 22, 2021</last_update_submitted>
  <last_update_submitted_qc>June 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01687205
org study id: MTN-011
secondary id: 3UM1AI068633
secondary id: UM1AI068615
secondary id: 11825
nct id: NCT01687205
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Study Objectives:

        -  To assess the impact of coitus (and semen) on the pharmacokinetics of tenofovir 1% gel
           in female genital tract secretions, vaginal and cervical tissue and rectal tract
           secretions

        -  To assess the impact of coitus (and semen) on pharmacodynamics of luminal drug by
           measuring the anti-HIV-1 activity in CVL samples

      Study Summary:

      MTN-011 will enroll heterosexual monogamous, sexually active couples, in which both partners
      are healthy and HIV-negative. The female participants must be between the ages of 21-46
      (inclusive) and currently using effective non-barrier contraception. Male participants must
      be 21 years of age or older. This Phase 1 expanded safety study will assess tenofovir PK in
      the genital tract secretions (CVL), rectal (rectal sponge) and both intracellular and
      extracellular tissue compartments (vaginal biopsy) in the absence of, or following coitus.
      Pharmacodynamics (antiviral activity) will also be assessed in CVL. MTN-011 will study the
      timing in which coitus might have the greatest impact on these variables, which is when gel
      is applied shortly prior to coitus in the absence of a drug reservoir.

      MTN-011 will examine PK/PD in response to a single dose of 1% tenofovir gel applied shortly
      before sex and compare to PK/PD assessments following a single gel application without sex.
      Additionally, data obtained from a visit in which participants do not dose with gel and do
      not have sex will serve as an additional control for the pharmacodynamic (PD) studies of the
      antiviral activity in CVL. If tenofovir retains its antiviral activity following sex, then
      the anti-HIV activity in CVL collected at the visit in which female participants dose with
      gel and have sex should be comparable to that of CVL collected at the visit in which females
      dose with gel and then do not engage in intercourse and significantly greater than the
      endogenous anti-HIV activity in CVL obtained at the visit in which participants do not dose
      with gel but do have sex and the visit in which no gel is administered and sex does occur.
      Data analysis performed after the completion of enrollment and follow-up procedures will
      demonstrate if there is an impact of coitus and semen on PK/PD when a single 1% tenofovir
      dose is applied shortly prior to sex.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Pharmacokinetics of tenofovir 1% gel
time frame: Visits 3b, 4b, 5b, 6b and 7b.
description: To assess the impact of coitus (and semen) on the pharmacokinetics of tenofovir 1% gel in female genital tract secretions, vaginal and cervical tissue and rectal tract secretions
measure: Pharmacodynamics of luminal drug
time frame: Visits 2b, 3b, 4b, 5b, 6b and 7b.
description: To assess the impact of coitus (and semen) on pharmacodynamics of luminal drug by measuring the anti-HIV-1 activity in CVL samples
measure: Acceptability
time frame: Visit 7b.
description: To assess the acceptability of the MTN-011 trial to male and female participants
measure: Impact of coitus and/or tenofovir on the genital tract mucosal environment
time frame: Visits 1, 2b, 3b, 4b, 5b, 6b and 7b.
description: To assess the impact of coitus and/or tenofovir on the genital tract musical environment
measure: Semen biomarker
time frame: Visits 1, 2b, 3b, 5b and 7b.
description: To determine whether a semen biomarker can be used to estimate the volume of ejaculate within CVL
measure: Retained drug levels in the lumen
time frame: Visits 1, 2b, 3b, 4b, 5b, 6b and 7b.
description: To assess whether sufficient drug is retained in the lumen in the absence of or following coitus to inhibit HSV-2 as an additional surrogate biomarker of pharmacodynamics
arm group label: Group 1
arm group type: Active Comparator
description: Single Dose/1 hour before and 1 hour after sex (BAT) Cohort
arm group label: Group 2
arm group type: Active Comparator
description: Multiple Dose Cohort
intervention type: Drug
intervention name: 1% Tenofovir Gel
arm group label: Group 1
arm group label: Group 2
criteria: 
gender: All
minimum age: 21 Years
maximum age: 46 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Betsy Herold, MD
role: Study Chair
affiliation: Albert Einstein College of Medicine
last name: Beatrice A. Chen, MD, MPH
role: Principal Investigator
affiliation: University of Pittsburgh
last name: Robert A. Salata, MD
role: Principal Investigator
affiliation: Case Western Reserve University
facility: 
facility: 
country: United States
citation: Herold BC, Chen BA, Salata RA, Marzinke MA, Kelly CW, Dezzutti CS, McGowan I, Galaska B, Levy L, Piper JM, Hillier S, Hendrix CW. Impact of Sex on the Pharmacokinetics and Pharmacodynamics of 1% Tenofovir Gel. Clin Infect Dis. 2016 Feb 1;62(3):375-382. doi: 10.1093/cid/civ913. Epub 2015 Oct 27.
PMID: 26508513
responsible party type: Sponsor
mesh term: Tenofovir