<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/NCT02199613</url>
  </required_header>
  <id_info>
    <org_study_id>H14-00490</org_study_id>
    <secondary_id>H14-00490</secondary_id>
    <nct_id>NCT02199613</nct_id>
  </id_info>
  <brief_title>Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir Treatment Simplification Strategy</brief_title>
  <acronym>QuaDar</acronym>
  <official_title>Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir in Treatment-experienced Patients: Quality Control Monitoring of a Treatment Simplification Strategy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of British Columbia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study aims to assess the safety and efficacy of darunavir 800mg plus the co-formulated&#xD;
      elvitegravir/cobicistat/tenofovir disoproxil fumarate (DF)/emtricitabine (Stribild) tablet as&#xD;
      a simplification strategy for the treatment of HIV infection in HIV-infected subjects who&#xD;
      have had previous antiretroviral treatment experience with multiple-drug regimens.&#xD;
&#xD;
      We hypothesize that elvitegravir/cobicistat/tenofovir DF/emtricitabine with darunavir will&#xD;
      offer a safe and efficacious treatment simplification strategy for HIV positive patients&#xD;
      currently receiving multiple-drug regimens to control their HIV infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible, consenting subjects will be assessed at baseline and weeks 2, 12, 24, 36, and 48.&#xD;
      Study medications will be dispensed at all visits except week 2, and all participants will&#xD;
      commence taking open-label darunavir 800mg in conjunction with the co-formulated tenofovir&#xD;
      DF/emtricitabine/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily&#xD;
      with food, following study procedures at baseline.&#xD;
&#xD;
      Assessments at the study visits will include:&#xD;
&#xD;
        1. Complete physical exam including height and weight at baseline; symptom-directed&#xD;
           physical exam and weight at other visits&#xD;
&#xD;
        2. Adverse clinical events including serious adverse events (hospitalizations etc.) and&#xD;
           medication changes at every visit.&#xD;
&#xD;
        3. HIV RNA every 4 weeks.&#xD;
&#xD;
        4. CD4 and CD8 absolute counts and % at all visits except week 2.&#xD;
&#xD;
        5. Platelet count, aspartate amino transferase (AST), creatinine, estimated glomerular&#xD;
           filtration rate (eGFR), phosphorus, urinalysis, and urine albumin to creatinine ratio&#xD;
           (UACR) at each visit.&#xD;
&#xD;
        6. Fasting lipids (total, HDL, and LDL cholesterol and triglycerides), apolipoprotein B,&#xD;
           high-sensitivity C- reactive protein (hsCRP) at baseline, week 24, and week 48.&#xD;
&#xD;
        7. Pregnancy test for women of child-bearing potential (as defined above) at every visit&#xD;
           except week 2. In addition, pregnancy tests will be performed monthly for women of&#xD;
           child-bearing potential; between study visits these may be done at home.&#xD;
&#xD;
        8. A plasma sample (3 mL) will be collected and stored once at baseline for all subjects,&#xD;
           and used for measurement of darunavir trough (pre-dose) concentration in subjects&#xD;
           receiving darunavir in their pre-study regimen.&#xD;
&#xD;
        9. All subjects will take their study medication under observation in the clinic on Day 14,&#xD;
           and plasma samples (3mL) for pharmacokinetic testing will be drawn immediately pre-dose&#xD;
           and at 1, 2, 3, 4, 5, 6, and 8 hours post-dose. Subjects will return the following day&#xD;
           before taking their Day 15 dose for a 24-hour post-dose sample.&#xD;
&#xD;
       10. Peripheral blood mononuclear cells (PBMCs) will be collected and stored at baseline for&#xD;
           possible future study-related testing.&#xD;
&#xD;
       11. The following questionnaires will be completed by participants prior to other study&#xD;
           procedures at baseline and at weeks 24 and 48: MOS-HIV quality of life questionnaire;&#xD;
           HIVTSQ; ACTG treatment adherence questionnaire; and the medication adherence self-report&#xD;
           inventory (MASRI).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">February 14, 2017</completion_date>
  <primary_completion_date type="Actual">February 14, 2017</primary_completion_date>
  <phase>Phase 4</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>Plasma HIV RNA</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of individuals with plasma HIV RNA &lt;200copies/mL at 12 weeks following regimen switch</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>plasma HIV RNA</measure>
    <time_frame>weeks 12, 24 and 48</time_frame>
    <description>Proportion of individuals with plasma HIV RNA &lt; 50 copies/mL at weeks 12, 24 and 48 post switch</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>plasma HIV RNA</measure>
    <time_frame>week 24 and 48</time_frame>
    <description>Proportion of individuals with plasma HIV RNA &lt; 200 copies/mL at week 24 and 48 post switch</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD4 cell count, CD4% and CD4/CD8 ratio</measure>
    <time_frame>12, 24 and 48 weeks</time_frame>
    <description>Change in CD4 cell count, CD4% and CD4/CD8 ratio from study baseline to 12, 24 and 48 weeks after switch.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>serum creatinine and estimated glomerular filtration rate (eGFR)</measure>
    <time_frame>12, 24, and 48 weeks</time_frame>
    <description>Change in serum creatinine and eGFR from baseline to 12, 24 weeks and 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event discontinuations</measure>
    <time_frame>48 weeks</time_frame>
    <description>Proportion of adverse events experienced necessitating switch to original regimen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP)</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Changes in fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP) between baseline and 24 and 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Darunavir plasma concentration</measure>
    <time_frame>week 2</time_frame>
    <description>Change in darunavir trough concentration from baseline to week 2 for individuals receiving darunavir at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores)</measure>
    <time_frame>weeks 24 and 48</time_frame>
    <description>Changes in HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores) between baseline and weeks 24 and 48 following switch.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Changes in antiretroviral adherence from baseline to 24 and 48 weeks. Adherence will be assessed using two measures: the ACTG treatment adherence questionnaire and the Medication adherence self-report inventory (MASRI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elvitegravir plasma concentrations</measure>
    <time_frame>Day 14</time_frame>
    <description>Elvitegravir concentrations will be measured at day 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>48 weeks</time_frame>
    <description>Adverse events necessitating a resumption of the previous antiretroviral regimen, and all serious adverse events will be recorded.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>HIV Infection</condition>
  <arm_group>
    <arm_group_label>Treatment simplification</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open-label darunavir 800mg in conjunction with the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily with food</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment simplification</intervention_name>
    <description>Eligible, consenting subjects will start open-label darunavir 800mg plus the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet once daily with food, following the study procedures at the baseline visit. They will be assessed at weeks 2, 12, 24, 36, and 48 after starting the new regimen.</description>
    <arm_group_label>Treatment simplification</arm_group_label>
    <other_name>Darunavir 800mg plus Stribild tablet once daily</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV positive adults &gt; or = 19 years of age&#xD;
&#xD;
          -  receiving stable therapy including one or two nucleoside/nucleotide reverse&#xD;
             transcriptase inhibitors (NRTIs), in conjunction with a once-daily protease inhibitor&#xD;
             (PI) (atazanavir, lopinavir or darunavir) and twice daily raltegravir or once daily&#xD;
             dolutegravir&#xD;
&#xD;
          -  Virologic suppression for &gt;6 months, defined as plasma viral load (VL) consistently &lt;&#xD;
             200 copies/mL with no evidence of prior virologic rebound (VL &gt; 1000 copies/mL) on the&#xD;
             NRTI/PI/Raltegravir regimen, AND VL &lt; 50 copies/mL at time of study screening&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &gt; o r= 70mL/min at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior documented viral rebound &gt; 1000 copies/mL on any raltegravir-containing regimen&#xD;
&#xD;
          -  Evidence of resistance mutations compromising raltegravir or elvitegravir activity on&#xD;
             prior genotypes.&#xD;
&#xD;
          -  Evidence of clinically significant resistance to tenofovir on any previous genotype&#xD;
             tests: K65R mutation, or 3 or more thymidine-analogue associated mutations (TAMS)&#xD;
             compromising tenofovir activity&#xD;
&#xD;
          -  Evidence of resistance mutations significantly compromising darunavir activity on any&#xD;
             previous genotypic tests&#xD;
&#xD;
          -  Current use of any nonnucleoside reverse transcriptase inhibitor (NNRTI)&#xD;
&#xD;
          -  Pregnancy or breast-feeding&#xD;
&#xD;
          -  Contraindications to tenofovir/FTC, elvitegravir, or cobicistat (e.g. previous&#xD;
             significant toxicity, intolerance or drug interactions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Hull, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Paul's Hospital Immunodeficiency Clinic</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z 1Y6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <last_update_submitted>November 1, 2017</last_update_submitted>
  <last_update_submitted_qc>November 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of British Columbia</investigator_affiliation>
    <investigator_full_name>Mark Hull</investigator_full_name>
    <investigator_title>Clinical Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>antiretroviral therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Darunavir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02199613
org study id: H14-00490
secondary id: H14-00490
nct id: NCT02199613
lead sponsor: 
collaborator: 
has dmc: No
The study aims to assess the safety and efficacy of darunavir 800mg plus the co-formulated
      elvitegravir/cobicistat/tenofovir disoproxil fumarate (DF)/emtricitabine (Stribild) tablet as
      a simplification strategy for the treatment of HIV infection in HIV-infected subjects who
      have had previous antiretroviral treatment experience with multiple-drug regimens.

      We hypothesize that elvitegravir/cobicistat/tenofovir DF/emtricitabine with darunavir will
      offer a safe and efficacious treatment simplification strategy for HIV positive patients
      currently receiving multiple-drug regimens to control their HIV infection.
Eligible, consenting subjects will be assessed at baseline and weeks 2, 12, 24, 36, and 48.
      Study medications will be dispensed at all visits except week 2, and all participants will
      commence taking open-label darunavir 800mg in conjunction with the co-formulated tenofovir
      DF/emtricitabine/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily
      with food, following study procedures at baseline.

      Assessments at the study visits will include:

        1. Complete physical exam including height and weight at baseline; symptom-directed
           physical exam and weight at other visits

        2. Adverse clinical events including serious adverse events (hospitalizations etc.) and
           medication changes at every visit.

        3. HIV RNA every 4 weeks.

        4. CD4 and CD8 absolute counts and % at all visits except week 2.

        5. Platelet count, aspartate amino transferase (AST), creatinine, estimated glomerular
           filtration rate (eGFR), phosphorus, urinalysis, and urine albumin to creatinine ratio
           (UACR) at each visit.

        6. Fasting lipids (total, HDL, and LDL cholesterol and triglycerides), apolipoprotein B,
           high-sensitivity C- reactive protein (hsCRP) at baseline, week 24, and week 48.

        7. Pregnancy test for women of child-bearing potential (as defined above) at every visit
           except week 2. In addition, pregnancy tests will be performed monthly for women of
           child-bearing potential; between study visits these may be done at home.

        8. A plasma sample (3 mL) will be collected and stored once at baseline for all subjects,
           and used for measurement of darunavir trough (pre-dose) concentration in subjects
           receiving darunavir in their pre-study regimen.

        9. All subjects will take their study medication under observation in the clinic on Day 14,
           and plasma samples (3mL) for pharmacokinetic testing will be drawn immediately pre-dose
           and at 1, 2, 3, 4, 5, 6, and 8 hours post-dose. Subjects will return the following day
           before taking their Day 15 dose for a 24-hour post-dose sample.

       10. Peripheral blood mononuclear cells (PBMCs) will be collected and stored at baseline for
           possible future study-related testing.

       11. The following questionnaires will be completed by participants prior to other study
           procedures at baseline and at weeks 24 and 48: MOS-HIV quality of life questionnaire;
           HIVTSQ; ACTG treatment adherence questionnaire; and the medication adherence self-report
           inventory (MASRI).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Plasma HIV RNA
time frame: 12 weeks
description: Proportion of individuals with plasma HIV RNA <200copies/mL at 12 weeks following regimen switch
measure: plasma HIV RNA
time frame: weeks 12, 24 and 48
description: Proportion of individuals with plasma HIV RNA < 50 copies/mL at weeks 12, 24 and 48 post switch
measure: plasma HIV RNA
time frame: week 24 and 48
description: Proportion of individuals with plasma HIV RNA < 200 copies/mL at week 24 and 48 post switch
measure: CD4 cell count, CD4% and CD4/CD8 ratio
time frame: 12, 24 and 48 weeks
description: Change in CD4 cell count, CD4% and CD4/CD8 ratio from study baseline to 12, 24 and 48 weeks after switch.
measure: serum creatinine and estimated glomerular filtration rate (eGFR)
time frame: 12, 24, and 48 weeks
description: Change in serum creatinine and eGFR from baseline to 12, 24 weeks and 48 weeks.
measure: Adverse event discontinuations
time frame: 48 weeks
description: Proportion of adverse events experienced necessitating switch to original regimen
measure: fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP)
time frame: 24 and 48 weeks
description: Changes in fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP) between baseline and 24 and 48 weeks.
measure: Darunavir plasma concentration
time frame: week 2
description: Change in darunavir trough concentration from baseline to week 2 for individuals receiving darunavir at baseline
measure: HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores)
time frame: weeks 24 and 48
description: Changes in HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores) between baseline and weeks 24 and 48 following switch.
measure: Adherence
time frame: 24 and 48 weeks
description: Changes in antiretroviral adherence from baseline to 24 and 48 weeks. Adherence will be assessed using two measures: the ACTG treatment adherence questionnaire and the Medication adherence self-report inventory (MASRI).
measure: Elvitegravir plasma concentrations
time frame: Day 14
description: Elvitegravir concentrations will be measured at day 14
measure: Adverse events
time frame: 48 weeks
description: Adverse events necessitating a resumption of the previous antiretroviral regimen, and all serious adverse events will be recorded.
arm group label: Treatment simplification
arm group type: Experimental
description: Open-label darunavir 800mg in conjunction with the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily with food
intervention type: Drug
intervention name: Treatment simplification
description: Eligible, consenting subjects will start open-label darunavir 800mg plus the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet once daily with food, following the study procedures at the baseline visit. They will be assessed at weeks 2, 12, 24, 36, and 48 after starting the new regimen.
arm group label: Treatment simplification
other name: Darunavir 800mg plus Stribild tablet once daily
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Hull, MD
role: Principal Investigator
affiliation: University of British Columbia
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of British Columbia
investigator full name: Mark Hull
investigator title: Clinical Assistant Professor
mesh term: HIV Infections
mesh term: Darunavir