<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/NCT01721109</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-236-0112</org_study_id>
    <secondary_id>2015-000313-40</secondary_id>
    <nct_id>NCT01721109</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents</brief_title>
  <official_title>A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/ Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</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 primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK)&#xD;
      and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil&#xD;
      fumarate (EVG/COBI/FTC/TDF) single-tablet regimen (STR) (Part A) and to evaluate the safety&#xD;
      and tolerability of EVG/COBI/FTC/TDF STR through Week 48 (Part B) in HIV-1 infected,&#xD;
      antiretroviral (ARV) treatment-naive adolescents.&#xD;
&#xD;
      A total of 50 adolescent participants (12 to &lt; 18 years of age) will be enrolled to receive&#xD;
      EVG/COBI/FTC/TDF as follows:&#xD;
&#xD;
        -  Part A: Twelve to 16 eligible participants will be enrolled to evaluate steady-state PK,&#xD;
           and confirm the dose, with the intent to enroll at least 4 participants 12 to &lt; 15 and&#xD;
           at least 4 participants 15 to &lt; 18 years of age.&#xD;
&#xD;
        -  Part B: Following confirmation of EVG exposure in at least 12 participants from Part A,&#xD;
           34 to 38 participants in addition to those enrolled in Part A will be enrolled to&#xD;
           evaluate the safety, tolerability, and antiviral activity of EVG/COBI/FTC/TDF STR.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2012</start_date>
  <completion_date type="Actual">January 29, 2018</completion_date>
  <primary_completion_date type="Actual">October 22, 2015</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG</measure>
    <time_frame>Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10</time_frame>
    <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)</measure>
    <time_frame>Up to Week 48 plus 30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI</measure>
    <time_frame>Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10</time_frame>
    <description>Ctau is defined as the observed drug concentration at the end of the dosing interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI</measure>
    <time_frame>Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10</time_frame>
    <description>Cmax is defined as the maximum concentration of drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI</measure>
    <time_frame>Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10</time_frame>
    <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With HIV-1 RNA &lt; 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis</measure>
    <time_frame>Weeks 24 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With HIV-1 RNA &lt; 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis</measure>
    <time_frame>Weeks 24 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48</measure>
    <time_frame>Baseline; Weeks 24 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in CD4+ Cell Count at Weeks 24 and 48</measure>
    <time_frame>Baseline; Weeks 24 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in CD4 Percentage at Weeks 24 and 48</measure>
    <time_frame>Baseline; Weeks 24 and 48</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Acquired Immunodeficiency Syndrome</condition>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>EVG/COBI/FTC/TDF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive treatment for 48 weeks and then had the option to enter an Extension Phase to receive EVG/COBI/FTC/TDF until 1) the age of 18, 2) EVG/COBI/FTC/TDF becomes commercially available in the country the participant is enrolled, or 3) Gilead elects to terminate the development of EVG/COBI/FTC/TDF in that country.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EVG/COBI/FTC/TDF</intervention_name>
    <description>150/150/200/300 mg STR administered orally once daily with food</description>
    <arm_group_label>EVG/COBI/FTC/TDF</arm_group_label>
    <other_name>Stribild®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  12 years to &lt; 18 years of age at baseline&#xD;
&#xD;
          -  Able to give written assent prior to any screening evaluations&#xD;
&#xD;
          -  Parent or guardian able to give written informed consent prior to any screening&#xD;
             evaluations and willing to comply with study requirements&#xD;
&#xD;
          -  Plasma HIV-1 RNA levels of ≥ 1,000 copies/mL&#xD;
&#xD;
          -  CD4+ cell count &gt; 100 cells/µL&#xD;
&#xD;
          -  Weight ≥ 35 kg (77 lbs)&#xD;
&#xD;
          -  Screening genotype report must show sensitivity to FTC and TDF&#xD;
&#xD;
          -  Able to swallow oral tablets&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Clinically normal ECG&#xD;
&#xD;
          -  Documented screening for active pulmonary tuberculosis per local standard of care&#xD;
             within 6 months of a screening visit&#xD;
&#xD;
          -  Hepatic transaminases ≤ 5 x upper limit of normal&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin&#xD;
&#xD;
          -  Individuals with a positive Hepatitis B surface antigen screening test can participate&#xD;
             in the study, providing that alternate therapy (other than TDF) for chronic Hepatitis&#xD;
             B infection is available as a part of local standard of care&#xD;
&#xD;
          -  Adequate hematologic function&#xD;
&#xD;
          -  Negative serum pregnancy test for all females&#xD;
&#xD;
          -  Males and females of childbearing potential must agree to utilize highly effective&#xD;
             contraception methods while on study treatment or agree to abstain from heterosexual&#xD;
             intercourse throughout the study period and for 30 days following the last dose of&#xD;
             study drug&#xD;
&#xD;
          -  Males must agree to utilize a highly effective method of contraception during&#xD;
             heterosexual intercourse throughout the study period and for 30 days following&#xD;
             discontinuation of investigational medicinal product&#xD;
&#xD;
          -  Must be willing and able to comply with all study requirements&#xD;
&#xD;
          -  Life expectancy ≥ 1 year&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  A new AIDS-defining condition diagnosed within the 30 days prior to screening&#xD;
&#xD;
          -  Prior treatment with any approved or investigational or experimental anti HIV-1 drug&#xD;
             for any length of time (other than that given for prevention of mother-to-child&#xD;
             transmission)&#xD;
&#xD;
          -  Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months&#xD;
             of the screening visit&#xD;
&#xD;
          -  Anticipated to require rifamycin treatment for mycobacterial infection while&#xD;
             participating in the study. Note: prophylactic Isoniazid (INH) therapy for latent&#xD;
             tuberculosis (TB) treatment is allowed.&#xD;
&#xD;
          -  Individuals experiencing decompensated cirrhosis&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
&#xD;
          -  Have any serious or active medical or psychiatric illness which would interfere with&#xD;
             treatment, assessment, or compliance with the protocol. This would include&#xD;
             uncontrolled renal, cardiac, hematological, hepatic, pulmonary, endocrine, central&#xD;
             nervous, gastrointestinal, vascular, metabolic, immunodeficiency disorders, active&#xD;
             infection, or malignancy that are clinically significant or requiring treatment within&#xD;
             30 days prior to the study dosing.&#xD;
&#xD;
          -  Current alcohol or substance abuse that will potentially interfere with compliance&#xD;
&#xD;
          -  Have history of significant drug sensitivity or drug allergy&#xD;
&#xD;
          -  Known hypersensitivity to the study drugs, the metabolites or formulation excipients&#xD;
&#xD;
          -  Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3&#xD;
             months of study screening or expected to receive these agents during the study&#xD;
&#xD;
          -  A history of malignancy within the past 5 years or ongoing malignancy other than&#xD;
             cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous&#xD;
             squamous carcinoma&#xD;
&#xD;
          -  Have previously participated in an investigational trial involving administration of&#xD;
             any investigational agent within 30 days prior to the study dosing&#xD;
&#xD;
          -  Participation in any other clinical trial without prior approval from sponsor is&#xD;
             prohibited while participating in this trial&#xD;
&#xD;
          -  Receiving ongoing therapy with any disallowed medications, including drugs not to be&#xD;
             used with EVG, COBI, FTC, TDF or individuals with any known allergies to the&#xD;
             excipients of EVG/COBI/FTC/TDF STR tablets&#xD;
&#xD;
        Note: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>East Bay AIDS Center Medical Group</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida - Department of Pediatrics</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Christopher's Hospital for Children</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rahima Moosa Mother and Child Hospital (Wits)</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2112</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr Latiff Private Practice</name>
      <address>
        <city>Durban</city>
        <state>Kwazulu-Natal</state>
        <zip>4001</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Desmond Tutu HIV Research Centre</name>
      <address>
        <city>Cape Town</city>
        <zip>7925</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mpati Medical Center</name>
      <address>
        <city>Dundee</city>
        <zip>3000</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical HIV Research Unit</name>
      <address>
        <city>Johannesburg</city>
        <zip>2092</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Perinatal HIV Research Unit</name>
      <address>
        <city>Soweto</city>
        <zip>2013</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Stellenbosch</name>
      <address>
        <city>Stellenbosch</city>
        <zip>7602</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siriraj Hospital, Mahidol University</name>
      <address>
        <city>Bangkok</city>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Savang Vadhana Memorial Hospital</name>
      <address>
        <city>Chon Buri</city>
        <zip>20110</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Srinakarind Hospital</name>
      <address>
        <city>Khon Kaen</city>
        <zip>40002</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
    <country>Thailand</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Mexico</country>
  </removed_countries>
  <results_reference>
    <citation>Gaur A, Fourie J, Chokephaibulkit K, Bekker L-G, Yin X, Custodio J, Bennett S, Cheng A, Quirk E. Pharmacokinetics, Efficacy and Safety of an Integrase Inhibitor-Based Single-Tablet Regimen in HIV-Infected Treatment-Naïve Adolescents. 21st Conference on Retroviruses and Opportunistic Infections (CROI). March 2014. Boston, MA, USA</citation>
  </results_reference>
  <results_reference>
    <citation>Chokephaibulkit K, Gaur A, Fourie J, Bekker L-G, Shao Y, Custodio J, Bennett S, Cheng A, Quirk E. Safety and Efficacy of the Integrase Inhibitor-Based Stribild Single-Tablet Regimen in HIV-Infected Adolescents Through 24 Weeks of Treatment. 20th International AIDS Conference. July 2014. Melbourne, Australia</citation>
  </results_reference>
  <results_reference>
    <citation>Porter DP, Bennett S, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). February 2015. Seattle, WA, USA</citation>
  </results_reference>
  <results_reference>
    <citation>Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, Bekker LG, Shao Y, Bennett S, Quirk E. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). 8th IAS Conference on HIV Pathogenesis, Treatment &amp; Prevention. July 2015. Vancouver, Canada</citation>
  </results_reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 4, 2012</study_first_posted>
  <results_first_submitted>February 24, 2017</results_first_submitted>
  <results_first_submitted_qc>February 24, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 10, 2017</results_first_posted>
  <disposition_first_submitted>August 17, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>August 18, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">August 19, 2016</disposition_first_posted>
  <last_update_submitted>July 20, 2018</last_update_submitted>
  <last_update_submitted_qc>July 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adolescents</keyword>
  <keyword>HIV-1</keyword>
  <keyword>HIV</keyword>
  <keyword>Treatment Naive</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at study sites in the United States, South Africa, and Thailand. The first participant was screened on 06 December 2012. The last study visit occurred on 29 January 2018.</recruitment_details>
      <pre_assignment_details>56 participants were screened.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>EVG/COBI/FTC/TDF</title>
          <description>Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) (150/150/200/300 mg) single-tablet regimen (STR) administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43">34 participants transitioned to commercial Stribild or to an individual patient use (IPU) program</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non- Compliance with Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrew Consent</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set: all participants who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>EVG/COBI/FTC/TDF</title>
          <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="50"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15" spread="1.5"/>
                  </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="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Permitted</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>South Africa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thailand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HIV-1 RNA</title>
          <units>log10 copies/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.60" spread="0.551"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HIV-1 RNA Category</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>≤ 100,000 copies/mL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt; 100,000 copies/mL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CD4 Cell Count</title>
          <units>cells/µL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="399" spread="127.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>CD4 Cell Count Category</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>≤ 199 cells/µL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>200 ≥ and ≤ 349 cells/µL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>350 ≥ and ≤ 499 cells/µL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥ 500 cells/µL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG</title>
        <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
        <time_frame>Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10</time_frame>
        <population>PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG</title>
          <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
          <population>PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.</population>
          <units>ng•h/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31620.9" spread="13978.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>A sample size of 14 participants was estimated to provide over 95% power to show pharmacokinetic equivalence between adult and adolescent participants. EVG population PK from historical adult data was used for comparison. The inter-subject standard deviation (natural log scale) of EVG AUCtau observed in the population PK data was 0.31 (historical data).</non_inferiority_desc>
            <param_type>Geometric least squares mean ratio</param_type>
            <param_value>1.3029</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.0479</ci_lower_limit>
            <ci_upper_limit>1.6200</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)</title>
        <time_frame>Up to Week 48 plus 30 days</time_frame>
        <population>Safety Analysis Set: all participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)</title>
          <population>Safety Analysis Set: all participants who received at least 1 dose of study drug.</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="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI</title>
        <description>Ctau is defined as the observed drug concentration at the end of the dosing interval.</description>
        <time_frame>Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10</time_frame>
        <population>PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI</title>
          <description>Ctau is defined as the observed drug concentration at the end of the dosing interval.</description>
          <population>PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>EVG</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="579.3" spread="455.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FTC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="102.6" spread="30.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TFV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.6" spread="23.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>COBI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.7" spread="68.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI</title>
        <description>Cmax is defined as the maximum concentration of drug.</description>
        <time_frame>Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10</time_frame>
        <population>PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI</title>
          <description>Cmax is defined as the maximum concentration of drug.</description>
          <population>PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>EVG</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2624.3" spread="1239.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FTC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2217.4" spread="664.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TFV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="438.5" spread="170.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>COBI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1500.4" spread="975.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI</title>
        <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
        <time_frame>Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10</time_frame>
        <population>PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI</title>
          <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
          <population>PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.</population>
          <units>ng•h/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FTC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15136.5" spread="4702.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TFV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4450.7" spread="1312.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>COBI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11884.8" spread="11220.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With HIV-1 RNA &lt; 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis</title>
        <time_frame>Weeks 24 and 48</time_frame>
        <population>Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With HIV-1 RNA &lt; 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis</title>
          <population>Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With HIV-1 RNA &lt; 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis</title>
        <time_frame>Weeks 24 and 48</time_frame>
        <population>Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With HIV-1 RNA &lt; 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis</title>
          <population>Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48</title>
        <time_frame>Baseline; Weeks 24 and 48</time_frame>
        <population>Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48</title>
          <population>Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.</population>
          <units>log10 copies/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Week 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.08" spread="0.922"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 48</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.16" spread="0.705"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in CD4+ Cell Count at Weeks 24 and 48</title>
        <time_frame>Baseline; Weeks 24 and 48</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in CD4+ Cell Count at Weeks 24 and 48</title>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>cells/µL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="178" spread="165.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="229" spread="245.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in CD4 Percentage at Weeks 24 and 48</title>
        <time_frame>Baseline; Weeks 24 and 48</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>EVG/COBI/FTC/TDF</title>
            <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in CD4 Percentage at Weeks 24 and 48</title>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>percentage</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" spread="4.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" spread="5.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to the last dose date plus 30 days (maximum exposure: 250.7 weeks)</time_frame>
      <desc>Safety Analysis Set: all participants who received at least 1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>EVG/COBI/FTC/TDF</title>
          <description>EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.1</default_vocab>
        <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="50"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Food poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Immune reconstitution inflammatory syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Disseminated tuberculosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Gastroenteritis shigella</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal behaviour</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.1</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="46" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Oropharyngeal gonococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Proctitis gonococcal</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Secondary syphilis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </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>After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:&#xD;
The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or&#xD;
The study has been completed at all study sites for at least 2 years</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gilead Clinical Study Information Center</name_or_title>
      <organization>Gilead Sciences</organization>
      <email>GileadClinicalTrials@gilead.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/NCT01721109
org study id: GS-US-236-0112
secondary id: 2015-000313-40
nct id: NCT01721109
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK)
      and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil
      fumarate (EVG/COBI/FTC/TDF) single-tablet regimen (STR) (Part A) and to evaluate the safety
      and tolerability of EVG/COBI/FTC/TDF STR through Week 48 (Part B) in HIV-1 infected,
      antiretroviral (ARV) treatment-naive adolescents.

      A total of 50 adolescent participants (12 to < 18 years of age) will be enrolled to receive
      EVG/COBI/FTC/TDF as follows:

        -  Part A: Twelve to 16 eligible participants will be enrolled to evaluate steady-state PK,
           and confirm the dose, with the intent to enroll at least 4 participants 12 to < 15 and
           at least 4 participants 15 to < 18 years of age.

        -  Part B: Following confirmation of EVG exposure in at least 12 participants from Part A,
           34 to 38 participants in addition to those enrolled in Part A will be enrolled to
           evaluate the safety, tolerability, and antiviral activity of EVG/COBI/FTC/TDF STR.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
time frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
measure: Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
time frame: Up to Week 48 plus 30 days
measure: For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
time frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
description: Ctau is defined as the observed drug concentration at the end of the dosing interval.
measure: For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
time frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
description: Cmax is defined as the maximum concentration of drug.
measure: For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
time frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
time frame: Weeks 24 and 48
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
time frame: Weeks 24 and 48
measure: Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
time frame: Baseline; Weeks 24 and 48
measure: Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
time frame: Baseline; Weeks 24 and 48
measure: Change From Baseline in CD4 Percentage at Weeks 24 and 48
time frame: Baseline; Weeks 24 and 48
arm group label: EVG/COBI/FTC/TDF
arm group type: Experimental
description: Participants will receive treatment for 48 weeks and then had the option to enter an Extension Phase to receive EVG/COBI/FTC/TDF until 1) the age of 18, 2) EVG/COBI/FTC/TDF becomes commercially available in the country the participant is enrolled, or 3) Gilead elects to terminate the development of EVG/COBI/FTC/TDF in that country.
intervention type: Drug
intervention name: EVG/COBI/FTC/TDF
description: 150/150/200/300 mg STR administered orally once daily with food
arm group label: EVG/COBI/FTC/TDF
other name: Stribild®
criteria: 
gender: All
minimum age: 12 Years
maximum age: 17 Years
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: South Africa
country: Thailand
country: United States
country: Mexico
citation: Gaur A, Fourie J, Chokephaibulkit K, Bekker L-G, Yin X, Custodio J, Bennett S, Cheng A, Quirk E. Pharmacokinetics, Efficacy and Safety of an Integrase Inhibitor-Based Single-Tablet Regimen in HIV-Infected Treatment-Naïve Adolescents. 21st Conference on Retroviruses and Opportunistic Infections (CROI). March 2014. Boston, MA, USA
citation: Chokephaibulkit K, Gaur A, Fourie J, Bekker L-G, Shao Y, Custodio J, Bennett S, Cheng A, Quirk E. Safety and Efficacy of the Integrase Inhibitor-Based Stribild Single-Tablet Regimen in HIV-Infected Adolescents Through 24 Weeks of Treatment. 20th International AIDS Conference. July 2014. Melbourne, Australia
citation: Porter DP, Bennett S, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). February 2015. Seattle, WA, USA
citation: Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, Bekker LG, Shao Y, Bennett S, Quirk E. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention. July 2015. Vancouver, Canada
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Acquired Immunodeficiency Syndrome
mesh term: Immunologic Deficiency Syndromes
mesh term: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 