<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/NCT02251236</url>
  </required_header>
  <id_info>
    <org_study_id>IN-US-236-1266</org_study_id>
    <nct_id>NCT02251236</nct_id>
  </id_info>
  <brief_title>Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals</brief_title>
  <official_title>Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University at Buffalo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The project will have two tracks, one for participants who are currently taking&#xD;
      elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or E/C/F/tenofovir&#xD;
      alafenamide (E/C/F/TDF or E/C/F/TAF) single-tablet regimen* (STR) (Track A) and one for&#xD;
      participants who will begin therapy with E/C/F/TDF or E/C/F/TAF STR during the study (Track&#xD;
      B).&#xD;
&#xD;
      Participants will take E/C/F/TDF and/or E/C/F/tenofovir alafenamide fumarate (E/C/F/TAF)&#xD;
      STR** (if available) for 24 weeks.&#xD;
&#xD;
      *Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and&#xD;
      300 mg of tenofovir disoproxil fumarate.&#xD;
&#xD;
      **Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine,&#xD;
      and 10 mg of tenofovir alafenamide fumarate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The proposed project will be a prospective, open-label treatment trial of 14 HIV-infected&#xD;
      adults. Participants will be enrolled in two tracks. Track A will enroll participants who&#xD;
      have been taking E/C/F/TDF to E/C/F/TAF for at least 12 weeks. Track B will enroll&#xD;
      participants who are not taking ART and no prior exposure to elvitegravir and no genotypic&#xD;
      drug resistance to any component of E/C/F/TDF to E/C/F/TAF. CSF and blood will be collected&#xD;
      twice in Track A (two on-treatment assessments) and three times in Track B (one&#xD;
      pre-treatment, two on-treatment assessments). If possible, we plan to time assessments to&#xD;
      bridge the transition from E/C/F/TDF to E/C/F/TAF so that all participants will ideally have&#xD;
      one CSF collection on each regimen, enabling a paired comparison of tenofovir concentrations&#xD;
      between the two tenofovir formulations. We estimate that 28 on-treatment CSF collections will&#xD;
      be sufficient to provide a small-sample estimate of the distribution of elvitegravir,&#xD;
      tenofovir and TAF into CSF.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2016</start_date>
  <completion_date type="Actual">January 18, 2017</completion_date>
  <primary_completion_date type="Actual">January 18, 2017</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline</measure>
    <time_frame>Baseline</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24</measure>
    <time_frame>Week 24</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentration of Tenofovir in Cerebrospinal Fluid at Baseline</measure>
    <time_frame>Baseline</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentration of Tenofovir in Cerebrospinal Fluid at Week 24</measure>
    <time_frame>Week 24</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Stribild Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Genvoya Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Untreated Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stribild</intervention_name>
    <description>To be administered orally, once daily with food.</description>
    <arm_group_label>Stribild Arm</arm_group_label>
    <arm_group_label>Untreated Arm</arm_group_label>
    <other_name>Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Genvoya</intervention_name>
    <description>To be administered orally, once daily with food.</description>
    <arm_group_label>Genvoya Arm</arm_group_label>
    <arm_group_label>Stribild Arm</arm_group_label>
    <arm_group_label>Untreated Arm</arm_group_label>
    <other_name>Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult men or women aged 18-60 years. Able and willing to provide informed consent.&#xD;
&#xD;
          -  Presence of HIV-1 infection as documented by a licensed ELISA test kit and confirmed&#xD;
             by Western blot or HIV RNA.&#xD;
&#xD;
          -  Track A (Currently taking E/C/F/TDF or E/C/F/TAF): Taking E/C/F/TDF or E/C/F/TAF for&#xD;
             at least 3 months prior to screening and undetectable plasma HIV-1 RNA (≤ 40&#xD;
             copies/mL)&#xD;
&#xD;
          -  Track B (Currently not taking ART): Off ART for at least 3 months. Prior exposure to&#xD;
             TDF and FTC will be allowed but subjects must not have primary genotypic drug&#xD;
             resistance mutations to elvitegravir, tenofovir, or emtricitabine (see Exclusion&#xD;
             Criteria)&#xD;
&#xD;
          -  Plasma HIV-1 RNA ≥ 5,000c/mL and CD4+ T-cell count ≥200cells/mm3.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Track B: Presence of primary drug resistance mutations for EVG, tenofovir, or&#xD;
             emtricitabine.&#xD;
&#xD;
          -  Use of drugs of abuse or alcohol which would interfere with adherence or completion of&#xD;
             this study. While on-study, subjects will be instructed not to consume alcohol for 48&#xD;
             hours prior to pharmacokinetic sampling days.&#xD;
&#xD;
          -  Pregnancy or breast-feeding. Women of childbearing potential must have a negative&#xD;
             serum or urine pregnancy test within 14 days prior to study entry and day of entry.&#xD;
&#xD;
          -  Chronic, severe, or other medical conditions that, in the opinion of the investigator,&#xD;
             would interfere with the subjects ability to participate in the protocol.&#xD;
&#xD;
          -  Use of prohibited protocol-specified drugs, prescription or over-the-counter, within&#xD;
             14 days prior to study entry.&#xD;
&#xD;
          -  Bleeding abnormality or other contraindication to lumbar puncture.&#xD;
&#xD;
          -  Moderate or severe cognitive impairment by history or based on Montreal Cognitive&#xD;
             Assessment.&#xD;
&#xD;
          -  Hepatitis B surface antigen (HBsAg) positive (Positive anti-HBs antibody and negative&#xD;
             HBsAg results are acceptable)&#xD;
&#xD;
          -  Hepatitis C antibody (HCV Ab) positive&#xD;
&#xD;
          -  Laboratory parameters documented within 21 days prior to study entry that would&#xD;
             increase the risk for adverse events:&#xD;
&#xD;
               1. Hemoglobin &lt; 12.5 g/dL for men; &lt; 11.5 g/dL for women;&#xD;
&#xD;
               2. Platelet count &lt; 100,000 platelets/mm3;&#xD;
&#xD;
               3. AST (SGOT) or ALT (SGPT) &gt; 1.5 x the upper limit of normal (ULN);&#xD;
&#xD;
               4. Estimated GFR&lt;70 ml/min&#xD;
&#xD;
               5. Weight less than 50 kg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Scott Letendre, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCSD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UC San Diego AntiViral Research Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 24, 2014</study_first_submitted>
  <study_first_submitted_qc>September 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <results_first_submitted>October 8, 2019</results_first_submitted>
  <results_first_submitted_qc>October 8, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 31, 2019</results_first_posted>
  <last_update_submitted>October 8, 2019</last_update_submitted>
  <last_update_submitted_qc>October 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 31, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Scott Letendre</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Stribild</keyword>
  <keyword>Genvoya</keyword>
  <keyword>elvitegravir</keyword>
  <keyword>Cerebrospinal Fluid</keyword>
  <keyword>HIV</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Emtricitabine</mesh_term>
    <mesh_term>Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination</mesh_term>
    <mesh_term>Cobicistat</mesh_term>
    <mesh_term>Emtricitabine tenofovir alafenamide</mesh_term>
    <mesh_term>Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination</mesh_term>
    <mesh_term>Elvitegravir</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 2, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02251236/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Stribild Arm</title>
          <description>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
        <group group_id="P2">
          <title>Genvoya Arm</title>
          <description>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
        <group group_id="P3">
          <title>Untreated Arm</title>
          <description>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>No participants enrolled in the Untreated Arm</population>
      <group_list>
        <group group_id="B1">
          <title>Stribild Arm</title>
          <description>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
        <group group_id="B2">
          <title>Genvoya Arm</title>
          <description>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
        <group group_id="B3">
          <title>Untreated Arm</title>
          <description>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
        <group group_id="B4">
          <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="9"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="0"/>
            <count group_id="B4" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="34" lower_limit="23" upper_limit="56"/>
                    <measurement group_id="B2" value="45" lower_limit="32" upper_limit="50"/>
                    <measurement group_id="B4" value="34.5" lower_limit="23" upper_limit="56"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B4" value="13"/>
                  </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="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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="B4" 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="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B4" value="12"/>
                  </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="B4" 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="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Plasma HIV RNA ≤ 40 copies/mL</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CD4+ T-cell Count</title>
          <units>cells/µL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="601" lower_limit="502" upper_limit="1071"/>
                    <measurement group_id="B2" value="784" lower_limit="262" upper_limit="944"/>
                    <measurement group_id="B4" value="717" lower_limit="262" upper_limit="1071"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline</title>
        <time_frame>Baseline</time_frame>
        <population>No participants enrolled in the Untreated Arm</population>
        <group_list>
          <group group_id="O1">
            <title>Stribild Arm</title>
            <description>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
          <group group_id="O2">
            <title>Genvoya Arm</title>
            <description>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
          <group group_id="O3">
            <title>Untreated Arm</title>
            <description>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline</title>
          <population>No participants enrolled in the Untreated Arm</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" lower_limit="3.11" upper_limit="5.20"/>
                    <measurement group_id="O2" value="2.72" lower_limit="1.75" upper_limit="3.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24</title>
        <time_frame>Week 24</time_frame>
        <population>No participants enrolled in the Untreated Arm</population>
        <group_list>
          <group group_id="O1">
            <title>Stribild Arm</title>
            <description>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
          <group group_id="O2">
            <title>Genvoya Arm</title>
            <description>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
          <group group_id="O3">
            <title>Untreated Arm</title>
            <description>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24</title>
          <population>No participants enrolled in the Untreated Arm</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.90" lower_limit="4.44" upper_limit="6.60"/>
                    <measurement group_id="O2" value="3.09" lower_limit="3.02" upper_limit="3.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Concentration of Tenofovir in Cerebrospinal Fluid at Baseline</title>
        <time_frame>Baseline</time_frame>
        <population>No participants enrolled in the Untreated Arm</population>
        <group_list>
          <group group_id="O1">
            <title>Stribild Arm</title>
            <description>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
          <group group_id="O2">
            <title>Genvoya Arm</title>
            <description>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
          <group group_id="O3">
            <title>Untreated Arm</title>
            <description>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Tenofovir in Cerebrospinal Fluid at Baseline</title>
          <population>No participants enrolled in the Untreated Arm</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.03" lower_limit="2.13" upper_limit="4.84"/>
                    <measurement group_id="O2" value="0.49" lower_limit="0.35" upper_limit="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Concentration of Tenofovir in Cerebrospinal Fluid at Week 24</title>
        <time_frame>Week 24</time_frame>
        <population>No participants enrolled in the Untreated Arm</population>
        <group_list>
          <group group_id="O1">
            <title>Stribild Arm</title>
            <description>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
          <group group_id="O2">
            <title>Genvoya Arm</title>
            <description>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
          <group group_id="O3">
            <title>Untreated Arm</title>
            <description>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Tenofovir in Cerebrospinal Fluid at Week 24</title>
          <population>No participants enrolled in the Untreated Arm</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.507" lower_limit="0.344" upper_limit="1.197"/>
                    <measurement group_id="O2" value="0.481" lower_limit="0.255" upper_limit="0.556"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 weeks</time_frame>
      <desc>No participants enrolled in the Untreated Arm so the number of participants at risk is zero</desc>
      <group_list>
        <group group_id="E1">
          <title>Stribild Arm</title>
          <description>Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
        <group group_id="E2">
          <title>Genvoya Arm</title>
          <description>Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
        <group group_id="E3">
          <title>Untreated Arm</title>
          <description>Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.&#xD;
Stribild: To be administered orally, once daily with food.&#xD;
Genvoya: To be administered orally, once daily with food.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache, Grade 3</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Creatinine Clearance Reduction, Grade 3</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="4" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia, Grade 1</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated Serum Glucose, Grade 1</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated Hepatic Alanine Transaminase, Grade 1</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Elevated Hepatic Aspartate Transaminase, Grade 2</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated Lactic Acid, Grade 1</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Elevated Creatine Kinase, Grade 2</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated Serum Bicarbonate, Grade 1</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Elevated Serum Creatinine, Grade 1 or 2</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hypernatremia, Grade 2</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Scott Letendre, Principal Investigator</name_or_title>
      <organization>University of California, San Diego</organization>
      <phone>6195438080</phone>
      <email>sletendre@ucsd.edu</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/NCT02251236
org study id: IN-US-236-1266
nct id: NCT02251236
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The project will have two tracks, one for participants who are currently taking
      elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or E/C/F/tenofovir
      alafenamide (E/C/F/TDF or E/C/F/TAF) single-tablet regimen* (STR) (Track A) and one for
      participants who will begin therapy with E/C/F/TDF or E/C/F/TAF STR during the study (Track
      B).

      Participants will take E/C/F/TDF and/or E/C/F/tenofovir alafenamide fumarate (E/C/F/TAF)
      STR** (if available) for 24 weeks.

      *Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and
      300 mg of tenofovir disoproxil fumarate.

      **Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine,
      and 10 mg of tenofovir alafenamide fumarate.
The proposed project will be a prospective, open-label treatment trial of 14 HIV-infected
      adults. Participants will be enrolled in two tracks. Track A will enroll participants who
      have been taking E/C/F/TDF to E/C/F/TAF for at least 12 weeks. Track B will enroll
      participants who are not taking ART and no prior exposure to elvitegravir and no genotypic
      drug resistance to any component of E/C/F/TDF to E/C/F/TAF. CSF and blood will be collected
      twice in Track A (two on-treatment assessments) and three times in Track B (one
      pre-treatment, two on-treatment assessments). If possible, we plan to time assessments to
      bridge the transition from E/C/F/TDF to E/C/F/TAF so that all participants will ideally have
      one CSF collection on each regimen, enabling a paired comparison of tenofovir concentrations
      between the two tenofovir formulations. We estimate that 28 on-treatment CSF collections will
      be sufficient to provide a small-sample estimate of the distribution of elvitegravir,
      tenofovir and TAF into CSF.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline
time frame: Baseline
measure: Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24
time frame: Week 24
measure: Concentration of Tenofovir in Cerebrospinal Fluid at Baseline
time frame: Baseline
measure: Concentration of Tenofovir in Cerebrospinal Fluid at Week 24
time frame: Week 24
arm group label: Stribild Arm
arm group type: Other
description: Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.
arm group label: Genvoya Arm
arm group type: Other
description: Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.
arm group label: Untreated Arm
arm group type: Other
description: Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.
intervention type: Drug
intervention name: Stribild
description: To be administered orally, once daily with food.
arm group label: Stribild Arm
arm group label: Untreated Arm
other name: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate
intervention type: Drug
intervention name: Genvoya
description: To be administered orally, once daily with food.
arm group label: Genvoya Arm
arm group label: Stribild Arm
arm group label: Untreated Arm
other name: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Scott Letendre, MD
role: Principal Investigator
affiliation: UCSD
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Scott Letendre
investigator title: Associate Professor of Medicine
mesh term: Tenofovir
mesh term: Emtricitabine
mesh term: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
mesh term: Cobicistat
mesh term: Emtricitabine tenofovir alafenamide
mesh term: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
mesh term: Elvitegravir
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 