<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/NCT02984852</url>
  </required_header>
  <id_info>
    <org_study_id>CR108258</org_study_id>
    <secondary_id>TMC114FD2HTX1004</secondary_id>
    <nct_id>NCT02984852</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Relative Bioavailability of Fixed-dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) as a Whole Tablet, as a Split Tablet, and as Crushed Tablet in Healthy Adult Participants</brief_title>
  <official_title>A Single-dose, Open-label, Randomized, Crossover Study to Assess the Relative Bioavailability of the Fixed-dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Administered Orally as a Whole Tablet, as a Split Tablet, and as Crushed Tablet in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Scientific Affairs, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Scientific Affairs, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the single-dose pharmacokinetics and relative&#xD;
      bioavailability of Darunavir (DRV) 800 milligram (mg), Cobicistat (COBI) 150 mg,&#xD;
      Emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg when administered as a&#xD;
      fixed-dose combination (FDC) (D/C/F/TAF) tablet in healthy adult participants when given as&#xD;
      Treatment A (reference): a single dose of D/C/F/TAF (800/150/200/10 mg) FDC tablet swallowed&#xD;
      as a whole, intact tablet with 240milliliter (mL) of noncarbonated water.Treatment B (test):&#xD;
      a single dose of D/C/F/TAF (800/150/200/10 mg) FDC tablet as a split tablet swallowed with&#xD;
      240 mL of noncarbonated water. Treatment C (test): a single dose of D/C/F/TAF (800/150/200/10&#xD;
      mg) FDC tablet as a crushed tablet mixed in 4 ounces (oz) of applesauce.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">February 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Up to Day 4</time_frame>
    <description>Cmax is defined as the maximum observed plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last])</measure>
    <time_frame>Up to Day 4</time_frame>
    <description>AUC (0-last) is the area under the Plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit [non BQL]) concentration, calculated by linear trapezoidal summation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity])</measure>
    <time_frame>Up to Day 4</time_frame>
    <description>The AUC (0-infinity) is the area under the plasma concentration time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Screening (21 days ) to End of the study (7 to 10 days after the last dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinical Laboratory Results as a Measure of Safety and Tolerability</measure>
    <time_frame>Screening (21 days ) to End of the study (7 to 10 days after the last dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Vital Signs as a Measure of Safety and Tolerability</measure>
    <time_frame>Screening (21 days ) to End of the study (7 to 10 days after the last dose)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Physical Examination Findings as a Measure of Safety and Tolerability</measure>
    <time_frame>Screening (21 days ) to End of the study (7 to 10 days after the last dose)</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment sequence ABC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral tablet of darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) Treatment A (whole tablet) as reference in session 1 then Treatment B(split tablet) as test in session 2 followed by Treatment C (crushed tablet mixed in applesauce) as test in session 3 under fed conditions (standardized breakfast) on Day 1 of each treatment session. There will be a washout period of at least 7 days between consecutive drug intakes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence ACB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment A in treatment session 1, then Treatment C in session 2 followed by Treatment B in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence BCA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment B in session 1 then Treatment C in session 2 followed by Treatment A in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence BAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment B in session 1 then Treatment A in session 2 followed by Treatment C in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence CAB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment C in session 1 then Treatment A in session 2 followed by Treatment B in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment sequence CBA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment C in session 1 then Treatment B in session 2 followed by Treatment A in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Darunavir (DRV)</intervention_name>
    <description>Darunavir 800 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/TAF(10mg).</description>
    <arm_group_label>Treatment sequence ABC</arm_group_label>
    <arm_group_label>Treatment sequence ACB</arm_group_label>
    <arm_group_label>Treatment sequence BAC</arm_group_label>
    <arm_group_label>Treatment sequence BCA</arm_group_label>
    <arm_group_label>Treatment sequence CAB</arm_group_label>
    <arm_group_label>Treatment sequence CBA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cobicistat (COBI)</intervention_name>
    <description>Cobicistat 150 milligram (mg) will be taken orally in FDC together with DRV(800mg)/FTC(200mg)/TAF(10mg).</description>
    <arm_group_label>Treatment sequence ABC</arm_group_label>
    <arm_group_label>Treatment sequence ACB</arm_group_label>
    <arm_group_label>Treatment sequence BAC</arm_group_label>
    <arm_group_label>Treatment sequence BCA</arm_group_label>
    <arm_group_label>Treatment sequence CAB</arm_group_label>
    <arm_group_label>Treatment sequence CBA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Emtricitabine (FTC)</intervention_name>
    <description>Emtricitabine 200 milligram (mg) will be taken orally in FDC together with COBI(150mg)/DRV(800mg)/TAF(10mg).</description>
    <arm_group_label>Treatment sequence ABC</arm_group_label>
    <arm_group_label>Treatment sequence ACB</arm_group_label>
    <arm_group_label>Treatment sequence BAC</arm_group_label>
    <arm_group_label>Treatment sequence BCA</arm_group_label>
    <arm_group_label>Treatment sequence CAB</arm_group_label>
    <arm_group_label>Treatment sequence CBA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir Alafenamide (TAF)</intervention_name>
    <description>Tenofovir Alafenamide 10 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/DRV(800mg).</description>
    <arm_group_label>Treatment sequence ABC</arm_group_label>
    <arm_group_label>Treatment sequence ACB</arm_group_label>
    <arm_group_label>Treatment sequence BAC</arm_group_label>
    <arm_group_label>Treatment sequence BCA</arm_group_label>
    <arm_group_label>Treatment sequence CAB</arm_group_label>
    <arm_group_label>Treatment sequence CBA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non-smoker for at least 3 months prior to selection&#xD;
&#xD;
          -  Body mass index (BMI) of 18.0 to 32 kilogram per square meter (kg/m^2), inclusive&#xD;
&#xD;
          -  Woman must have a negative highly sensitive serum (beta-human chorionic gonadotropin&#xD;
             [beta-hCG]) pregnancy test at screening and a negative sensitive urine pregnancy test&#xD;
             on Day -1 before the first dose of study drug&#xD;
&#xD;
          -  Woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted&#xD;
             reproduction during the study and for at least 90 days after receiving the last dose&#xD;
             of study drug&#xD;
&#xD;
          -  During the study and for a minimum of 1 spermatogenesis cycle (defined as&#xD;
             approximately 90 days) after receiving the last dose of study drug, a non-vasectomized&#xD;
             man who is sexually active with a woman of childbearing potential must agree to use a&#xD;
             highly effective barrier method of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positive human immunodeficiency virus -1 (HIV-1) or HIV-2 test at screening&#xD;
&#xD;
          -  Hepatitis A, B, or C infection, confirmed by a positive hepatitis A antibody&#xD;
             immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg), or hepatitis C virus&#xD;
             antibody (anti-HCV) test, respectively, at screening&#xD;
&#xD;
          -  History of renal insufficiency&#xD;
&#xD;
          -  History of significant drug-induced skin reactions (such as, but not limited, to&#xD;
             Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and/or erythema&#xD;
             multiforme) or history of allergies to drugs (such as, but not limited to,&#xD;
             sulfonamides and penicillins)&#xD;
&#xD;
          -  Previously participated in a multiple-dose study with Darunavir (DRV), Cobicistat&#xD;
             (COBI), Emtricitabine (FTC), Tenofovir Alafenamide (TAF), or Tenofovir Disoproxil&#xD;
             Fumarate (TDF)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Scientific Affairs, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Scientific Affairs, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <last_update_submitted>March 31, 2017</last_update_submitted>
  <last_update_submitted_qc>March 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crush Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Emtricitabine</mesh_term>
    <mesh_term>Darunavir</mesh_term>
    <mesh_term>Cobicistat</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/NCT02984852
org study id: CR108258
secondary id: TMC114FD2HTX1004
nct id: NCT02984852
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
The purpose of this study is to evaluate the single-dose pharmacokinetics and relative
      bioavailability of Darunavir (DRV) 800 milligram (mg), Cobicistat (COBI) 150 mg,
      Emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg when administered as a
      fixed-dose combination (FDC) (D/C/F/TAF) tablet in healthy adult participants when given as
      Treatment A (reference): a single dose of D/C/F/TAF (800/150/200/10 mg) FDC tablet swallowed
      as a whole, intact tablet with 240milliliter (mL) of noncarbonated water.Treatment B (test):
      a single dose of D/C/F/TAF (800/150/200/10 mg) FDC tablet as a split tablet swallowed with
      240 mL of noncarbonated water. Treatment C (test): a single dose of D/C/F/TAF (800/150/200/10
      mg) FDC tablet as a crushed tablet mixed in 4 ounces (oz) of applesauce.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Observed Plasma Concentration (Cmax)
time frame: Up to Day 4
description: Cmax is defined as the maximum observed plasma concentration.
measure: Area Under the Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last])
time frame: Up to Day 4
description: AUC (0-last) is the area under the Plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit [non BQL]) concentration, calculated by linear trapezoidal summation.
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
time frame: Up to Day 4
description: The AUC (0-infinity) is the area under the plasma concentration time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
time frame: Screening (21 days ) to End of the study (7 to 10 days after the last dose)
measure: Number of Participants With Clinical Laboratory Results as a Measure of Safety and Tolerability
time frame: Screening (21 days ) to End of the study (7 to 10 days after the last dose)
measure: Number of Participants With Vital Signs as a Measure of Safety and Tolerability
time frame: Screening (21 days ) to End of the study (7 to 10 days after the last dose)
measure: Number of Participants With Physical Examination Findings as a Measure of Safety and Tolerability
time frame: Screening (21 days ) to End of the study (7 to 10 days after the last dose)
arm group label: Treatment sequence ABC
arm group type: Experimental
description: Participants will receive a single oral tablet of darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) Treatment A (whole tablet) as reference in session 1 then Treatment B(split tablet) as test in session 2 followed by Treatment C (crushed tablet mixed in applesauce) as test in session 3 under fed conditions (standardized breakfast) on Day 1 of each treatment session. There will be a washout period of at least 7 days between consecutive drug intakes.
arm group label: Treatment sequence ACB
arm group type: Experimental
description: Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment A in treatment session 1, then Treatment C in session 2 followed by Treatment B in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.
arm group label: Treatment sequence BCA
arm group type: Experimental
description: Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment B in session 1 then Treatment C in session 2 followed by Treatment A in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.
arm group label: Treatment sequence BAC
arm group type: Experimental
description: Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment B in session 1 then Treatment A in session 2 followed by Treatment C in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.
arm group label: Treatment sequence CAB
arm group type: Experimental
description: Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment C in session 1 then Treatment A in session 2 followed by Treatment B in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.
arm group label: Treatment sequence CBA
arm group type: Experimental
description: Participants will receive a single oral tablet of D/C/F/TAF [FDC] Treatment C in session 1 then Treatment B in session 2 followed by Treatment A in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes.
intervention type: Drug
intervention name: Darunavir (DRV)
description: Darunavir 800 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/TAF(10mg).
arm group label: Treatment sequence ABC
arm group label: Treatment sequence ACB
arm group label: Treatment sequence BAC
arm group label: Treatment sequence BCA
arm group label: Treatment sequence CAB
arm group label: Treatment sequence CBA
intervention type: Drug
intervention name: Cobicistat (COBI)
description: Cobicistat 150 milligram (mg) will be taken orally in FDC together with DRV(800mg)/FTC(200mg)/TAF(10mg).
arm group label: Treatment sequence ABC
arm group label: Treatment sequence ACB
arm group label: Treatment sequence BAC
arm group label: Treatment sequence BCA
arm group label: Treatment sequence CAB
arm group label: Treatment sequence CBA
intervention type: Drug
intervention name: Emtricitabine (FTC)
description: Emtricitabine 200 milligram (mg) will be taken orally in FDC together with COBI(150mg)/DRV(800mg)/TAF(10mg).
arm group label: Treatment sequence ABC
arm group label: Treatment sequence ACB
arm group label: Treatment sequence BAC
arm group label: Treatment sequence BCA
arm group label: Treatment sequence CAB
arm group label: Treatment sequence CBA
intervention type: Drug
intervention name: Tenofovir Alafenamide (TAF)
description: Tenofovir Alafenamide 10 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/DRV(800mg).
arm group label: Treatment sequence ABC
arm group label: Treatment sequence ACB
arm group label: Treatment sequence BAC
arm group label: Treatment sequence BCA
arm group label: Treatment sequence CAB
arm group label: Treatment sequence CBA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Scientific Affairs, LLC Clinical Trial
role: Study Director
affiliation: Janssen Scientific Affairs, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Crush Injuries
mesh term: Tenofovir
mesh term: Emtricitabine
mesh term: Darunavir
mesh term: Cobicistat