<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/NCT03270969</url>
  </required_header>
  <id_info>
    <org_study_id>0491-17-FB</org_study_id>
    <nct_id>NCT03270969</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic Evaluation of Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis in Transgender Women</brief_title>
  <official_title>Pharmacokinetics of Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Pre-exposure Prophylaxis in Transgender Women Receiving Feminizing Hormone Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nebraska</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Nebraska</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Human immunodeficiency virus (HIV) persists worldwide as an immense health burden among&#xD;
      vulnerable populations. HIV pre-exposure prophylaxis (PrEP) has offered the promise of&#xD;
      limiting the global burden of HIV. The objective of this proposal is to conduct a&#xD;
      pharmacokinetic (PK) study in transgender women to describe the pharmacokinetics of tenofovir&#xD;
      disoproxil fumarate/emtricitabine (TDF/FTC) as PrEP within this population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PrEP is a critical component of comprehensive transgender medical care. The proposed&#xD;
      open-label, intensive PK study will inform the pharmacologic impact of combining PrEP and&#xD;
      concurrent feminizing hormone regimens. The investigators hypothesize transgender women will&#xD;
      achieve similar PrEP concentrations compared to the historical controls, and that hormone&#xD;
      concentrations (estrogen and testosterone) will not be affected. The aims of this study are&#xD;
      to (1) to determine if concurrent use of TDF/FTC as PrEP in combination with feminizing&#xD;
      hormones alters the PK of tenofovir (TFV) and FTC and (2) to determine if concurrent use of&#xD;
      PrEP with feminizing hormones alters serum estradiol and testosterone concentrations. To&#xD;
      achieve these aims, this study will enroll transgender women who are receiving either&#xD;
      oral/sublingual or transdermal estradiol with spironolactone. Using intensive PK sampling,&#xD;
      plasma and intracellular TDF/FTC concentrations will be measured after 14 days of oral&#xD;
      TDF/FTC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 5, 2018</start_date>
  <completion_date type="Actual">September 10, 2018</completion_date>
  <primary_completion_date type="Actual">September 10, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>TFV plasma exposure</measure>
    <time_frame>14 days</time_frame>
    <description>Intensive PK sampling compared to historical controls</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>FTC plasma exposure</measure>
    <time_frame>14 days</time_frame>
    <description>Intensive PK sampling compared to historical controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tenofovir-diphosphate (TFV-DP) intracellular concentrations</measure>
    <time_frame>14 days</time_frame>
    <description>Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emtricitabine-triphosphate (FTC-TP) intracellular concentrations</measure>
    <time_frame>14 days</time_frame>
    <description>Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFV maximum plasma concentration (Cmax)</measure>
    <time_frame>14 days</time_frame>
    <description>Cmax of TFV compared to historical control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FTC maximum plasma concentration (Cmax)</measure>
    <time_frame>14 days</time_frame>
    <description>Cmax of FTC compared to historical control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estradiol serum concentrations</measure>
    <time_frame>14 days</time_frame>
    <description>Before and after intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Testosterone serum concentrations</measure>
    <time_frame>14 days</time_frame>
    <description>Before and after intervention</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>HIV Prevention</condition>
  <arm_group>
    <arm_group_label>TDF/FTC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tenofovir Disoproxil Fumarate/Emtricitabine group HIV-uninfected transgender women receiving feminizing hormone therapy plus tenofovir disoproxil fumarate/emtricitabine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir Disoproxil Fumarate/Emtricitabine</intervention_name>
    <description>Participants will receive daily TDF/FTC for 14 days</description>
    <arm_group_label>TDF/FTC</arm_group_label>
    <other_name>Descovy and Truvada</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the participant has been informed of all pertinent aspects of the study.&#xD;
&#xD;
          -  Participants who are willing and able to comply with scheduled visits, treatment plan,&#xD;
             laboratory tests, and other study procedures.&#xD;
&#xD;
          -  Self identify as a transgender woman.&#xD;
&#xD;
          -  Receiving estradiol (oral/sublingual tablets or transdermal patches) with oral&#xD;
             spironolactone for at least 3 months prior to study entry.&#xD;
&#xD;
          -  Serum estradiol level &gt;100 pg/mL.&#xD;
&#xD;
          -  Non-reactive 4th or 5th generation screening test for HIV.&#xD;
&#xD;
          -  Adults (19 years or older).&#xD;
&#xD;
          -  Able to read and speak English to ensure appropriate ability to obtain informed&#xD;
             consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants will not be included in the study if one, or more, of the following&#xD;
             criteria are met:&#xD;
&#xD;
          -  Use of drugs known to be contraindicated with TDF, FTC, estradiol, or spironolactone&#xD;
             within 30 days of study entry. The study team will review all concomitant medications&#xD;
             at screening based on the US Department of Health and Human Services drug interaction&#xD;
             table and the drug product labeling.&#xD;
&#xD;
          -  Use of injectable estradiol (valerate or cypionate).&#xD;
&#xD;
          -  Presence of any active condition or clinically significant disease that, in the&#xD;
             investigator's opinion, would compromise the subject's safety or outcome of the study,&#xD;
             including qualifying for non-occupational post-HIV exposure prophylaxis.&#xD;
&#xD;
          -  Signs or symptoms of acute HIV infection within the last 30 days.&#xD;
&#xD;
          -  Laboratory values obtained within 30 days prior to study entry:&#xD;
&#xD;
          -  Creatinine clearance (CrCl) less than 60 mL/min as estimated by the Cockcroft-Gault&#xD;
             equation.&#xD;
&#xD;
          -  Positive hepatitis B surface antigen and/or hepatitis C antibody.&#xD;
&#xD;
          -  Alanine transaminase (ALT), Aspartate transaminase (AST) or alkaline phosphatase &gt; 5x&#xD;
             the upper limit of normal (ULN).&#xD;
&#xD;
          -  Hemoglobin &lt;10 g/dL.&#xD;
&#xD;
          -  Platelets &lt;50,000/mm3.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>transgender women</gender_description>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kimberly Scarsi, PharmD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nebraska</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>September 13, 2023</last_update_submitted>
  <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</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>
    <mesh_term>Emtricitabine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03270969
org study id: 0491-17-FB
nct id: NCT03270969
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Human immunodeficiency virus (HIV) persists worldwide as an immense health burden among
      vulnerable populations. HIV pre-exposure prophylaxis (PrEP) has offered the promise of
      limiting the global burden of HIV. The objective of this proposal is to conduct a
      pharmacokinetic (PK) study in transgender women to describe the pharmacokinetics of tenofovir
      disoproxil fumarate/emtricitabine (TDF/FTC) as PrEP within this population.
PrEP is a critical component of comprehensive transgender medical care. The proposed
      open-label, intensive PK study will inform the pharmacologic impact of combining PrEP and
      concurrent feminizing hormone regimens. The investigators hypothesize transgender women will
      achieve similar PrEP concentrations compared to the historical controls, and that hormone
      concentrations (estrogen and testosterone) will not be affected. The aims of this study are
      to (1) to determine if concurrent use of TDF/FTC as PrEP in combination with feminizing
      hormones alters the PK of tenofovir (TFV) and FTC and (2) to determine if concurrent use of
      PrEP with feminizing hormones alters serum estradiol and testosterone concentrations. To
      achieve these aims, this study will enroll transgender women who are receiving either
      oral/sublingual or transdermal estradiol with spironolactone. Using intensive PK sampling,
      plasma and intracellular TDF/FTC concentrations will be measured after 14 days of oral
      TDF/FTC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: TFV plasma exposure
time frame: 14 days
description: Intensive PK sampling compared to historical controls
measure: FTC plasma exposure
time frame: 14 days
description: Intensive PK sampling compared to historical controls
measure: Tenofovir-diphosphate (TFV-DP) intracellular concentrations
time frame: 14 days
description: Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control
measure: Emtricitabine-triphosphate (FTC-TP) intracellular concentrations
time frame: 14 days
description: Peripheral blood mononuclear cells (PBMC) concentrations compared to historical control
measure: TFV maximum plasma concentration (Cmax)
time frame: 14 days
description: Cmax of TFV compared to historical control
measure: FTC maximum plasma concentration (Cmax)
time frame: 14 days
description: Cmax of FTC compared to historical control
measure: Estradiol serum concentrations
time frame: 14 days
description: Before and after intervention
measure: Testosterone serum concentrations
time frame: 14 days
description: Before and after intervention
arm group label: TDF/FTC
arm group type: Experimental
description: Tenofovir Disoproxil Fumarate/Emtricitabine group HIV-uninfected transgender women receiving feminizing hormone therapy plus tenofovir disoproxil fumarate/emtricitabine
intervention type: Drug
intervention name: Tenofovir Disoproxil Fumarate/Emtricitabine
description: Participants will receive daily TDF/FTC for 14 days
arm group label: TDF/FTC
other name: Descovy and Truvada
criteria: 
gender: All
gender based: Yes
gender description: transgender women
minimum age: 19 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Kimberly Scarsi, PharmD, MS
role: Principal Investigator
affiliation: University of Nebraska
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tenofovir
mesh term: Emtricitabine