<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/NCT04431518</url>
  </required_header>
  <id_info>
    <org_study_id>ViiV Healthcare IIS 1837</org_study_id>
    <nct_id>NCT04431518</nct_id>
  </id_info>
  <brief_title>PK of JULUCA in Hemodialysis</brief_title>
  <official_title>The Steady-State Pharmacokinetics of Dolutegravir/Rilpivirine Fixed Dose Combination (FDC) in Patients With End Stage Renal Disease (ESRD) Requiring Hemodialysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will compare the pharmacokinetics of the component drugs in JULUCA, and HIV&#xD;
      combination treatment pill, in HIV-negative patients who require hemodialysis with those with&#xD;
      normal renal function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The pharmacokinetics of dolutegravir and rilpivirine, the components of JULUCA, in patients&#xD;
      with end stage renal disease requiring hemodialysis have not previously been adequately&#xD;
      studied. It is possible that the PK of these drugs are affected by renal failure which may&#xD;
      then compromise effectiveness and safety. This trial will rigorously assess the plasma PK and&#xD;
      protein-binding of these two drugs in 10 HIV-negative patients requiring hemodialysis with 10&#xD;
      matched persons with normal renal function. All participants will receive JULUCA for up to 14&#xD;
      days and then undergo a 24 hour intensive PK evaluation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 23, 2021</start_date>
  <completion_date type="Anticipated">August 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Matched case-control</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DTG Ctau</measure>
    <time_frame>11-14 days</time_frame>
    <description>Steady-state plasma Ctau for dolutegravir</description>
  </primary_outcome>
  <primary_outcome>
    <measure>RPV Ctau</measure>
    <time_frame>11-14 days</time_frame>
    <description>Steady-state plasma Ctau for rilpivirine</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of DTG and RPV</measure>
    <time_frame>26-30 days</time_frame>
    <description>The attributable adverse events associated with use of DTG and RPV will be assessed during the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DTG and RPV AUC</measure>
    <time_frame>11-14 days</time_frame>
    <description>Steady-state plasma AUC for dolutegravir and rilpivirine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DTG and RPV Cmax</measure>
    <time_frame>11-14 days</time_frame>
    <description>Steady-stage plasma Cmax for dolutegravir and rilpivirine</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>HIV/AIDS</condition>
  <condition>ESRD</condition>
  <arm_group>
    <arm_group_label>Hemodialysis Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Receipt of JULUCA one pill per day up to 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal Renal Function Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Receipt of JULUCA one pill per day up to 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JULUCA 50Mg-25Mg Tablet</intervention_name>
    <description>One dose of JULUCA will be taken daily for up to 14 days</description>
    <arm_group_label>Hemodialysis Group</arm_group_label>
    <arm_group_label>Normal Renal Function Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Negative HIV antibody testing at screening.&#xD;
&#xD;
          2. For the ESRD requiring HD study group: ESRD requiring chronic hemodialysis for at&#xD;
             least 6 months at an established center (not home dialysis).&#xD;
&#xD;
             NOTE: The approximate date that hemodialysis was initiated should be reported, if&#xD;
             known.&#xD;
&#xD;
             For the normal renal function group: Estimated CrCl (using the Cockcroft-Gault&#xD;
             equation) at screening ≥75mL/min.&#xD;
&#xD;
          3. Availability of alternative venous access (not used for dialysis) for the purpose of&#xD;
             PK sampling.&#xD;
&#xD;
          4. The following laboratory values obtained within 30 days prior to study entry (obtained&#xD;
             either at screening or done as part of routine clinical care):&#xD;
&#xD;
               -  AST (SGOT) and ALT (SGPT) less than or equal to ULN&#xD;
&#xD;
               -  Total bilirubin less than or equal to 1.5 x ULN&#xD;
&#xD;
               -  Hemoglobin greater than or equal to 8.0 mg/dL&#xD;
&#xD;
          5. A negative serum pregnancy test result at screening for all women of reproductive&#xD;
             potential who have not reached menopause or undergone hysterectomy, bilateral&#xD;
             oophorectomy, or tubal ligation.&#xD;
&#xD;
          6. Males and females, age 18-65 years.&#xD;
&#xD;
          7. Ability and willingness of participant or legal guardian/representative to provide&#xD;
             written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known allergy or hypersensitivity to either dolutegravir or rilpivirine&#xD;
&#xD;
          2. Use of peritoneal dialysis.&#xD;
&#xD;
          3. Serious illnesses, other than ESRD, requiring systemic treatment and/or&#xD;
             hospitalization within 30 days prior to the Screening Visit.&#xD;
&#xD;
          4. Known liver cirrhosis, unstable liver disease (presence of ascites, encephalopathy,&#xD;
             coagulopathy, esophageal/gastric varices), Child-Pugh Class A, B, or C, or known&#xD;
             biliary abnormalities (except for known Gilbert's syndrome or asymptomatic&#xD;
             gallstones).&#xD;
&#xD;
          5. Hepatitis B surface antigen or hepatitis C antibody with detectable RNA at screening.&#xD;
&#xD;
          6. Known gastrointestinal disease that may lead to poor absorption of the study drugs.&#xD;
&#xD;
          7. Known hereditary problems of galactose intolerance, total lactase deficiency, or&#xD;
             glucose-galactose malabsorption.&#xD;
&#xD;
          8. Any of the following gastrointestinal signs or symptoms of Grade ≥ 2 within 7 days&#xD;
             prior to the Screening Visit or during study drug administration prior to the&#xD;
             Intensive PK Study Visit:&#xD;
&#xD;
               -  nausea&#xD;
&#xD;
               -  vomiting&#xD;
&#xD;
               -  diarrhea&#xD;
&#xD;
               -  abdominal pain&#xD;
&#xD;
          9. Use of any of the following within 30 days of initiating study drug:&#xD;
&#xD;
               -  Medications known to appreciably inhibit or induce CYP3A enzymes, P-glycoprotein,&#xD;
                  or UGT1A1 or UGT1A4 enzymes (e.g., anticonvulsants such as carbamazepine,&#xD;
                  phenytoin, oxacarbamazepine; antimycobacterials such as rifampin, rifabutin and&#xD;
                  rifapentine; antifungal agents such as ketoconazole, fluconazole and&#xD;
                  itraconazole; verapamil, clarithromycin, erythromycin)&#xD;
&#xD;
               -  St. John's Wort, echinacea, grapefruits or grapefruit juice, garlic supplements,&#xD;
                  ginseng, golden seal, and milk thistle&#xD;
&#xD;
               -  Cancer chemotherapeutic agents&#xD;
&#xD;
               -  Investigational agents&#xD;
&#xD;
               -  Immunomodulators, including systemic steroids greater than or equal to 100 mg/day&#xD;
                  of prednisone (Note: Topical and inhaled corticosteroids are allowed.)&#xD;
&#xD;
               -  Dofetilide&#xD;
&#xD;
               -  Positive pre-study drug screen. Drugs that will be screened for include&#xD;
                  amphetamines, barbiturates, cocaine and phencyclidine (PCP). Active injected drug&#xD;
                  users will be excluded from this study.&#xD;
&#xD;
         10. Use of proton pump inhibitors within 7 days of initiating study drug (H2 blockers are&#xD;
             permitted).&#xD;
&#xD;
         11. Pregnancy and/or breast-feeding.&#xD;
&#xD;
         12. Moderate to severe depression, defined as a PHQ-9 ≥ 10 at Screening.&#xD;
&#xD;
         13. Significant change (i.e., more than a 50% change) in tobacco smoking habit within 6&#xD;
             weeks prior to the Screening Visit. Participants who have recently stopped smoking&#xD;
             should have stopped smoking more than 6 weeks prior to the Screening Visit.&#xD;
             Participants who have recently started smoking should have started more than 6 weeks&#xD;
             prior to the Screening Visit.&#xD;
&#xD;
         14. QTc interval greater than 500 msec at Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Samir K Gupta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Samir K Gupta, MD</last_name>
    <phone>317-274-7926</phone>
    <email>sgupta1@iu.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Samir Gupta</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Samir Gupta</last_name>
      <phone>317-274-7926</phone>
      <email>sgupta1@iu.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>May 16, 2023</last_update_submitted>
  <last_update_submitted_qc>May 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Samir K. Gupta, MD</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>ESRD</keyword>
  <keyword>Hemodialysis</keyword>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dolutegravir, rilpivirine drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD will provided upon request and approval by the investigators or through online data repositories such as Figshare.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>IPD will become available after publication of the data, anticipated to be by July 2022.</ipd_time_frame>
    <ipd_access_criteria>Fully available when posted to online repositories. Additional data upon request and approval by the study investigators. The financial sponsor will not have a role in this process.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 17, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT04431518/Prot_SAP_003.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 19, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT04431518/ICF_004.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04431518
org study id: ViiV Healthcare IIS 1837
nct id: NCT04431518
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study will compare the pharmacokinetics of the component drugs in JULUCA, and HIV
      combination treatment pill, in HIV-negative patients who require hemodialysis with those with
      normal renal function.
The pharmacokinetics of dolutegravir and rilpivirine, the components of JULUCA, in patients
      with end stage renal disease requiring hemodialysis have not previously been adequately
      studied. It is possible that the PK of these drugs are affected by renal failure which may
      then compromise effectiveness and safety. This trial will rigorously assess the plasma PK and
      protein-binding of these two drugs in 10 HIV-negative patients requiring hemodialysis with 10
      matched persons with normal renal function. All participants will receive JULUCA for up to 14
      days and then undergo a 24 hour intensive PK evaluation.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Matched case-control
primary purpose: Treatment
masking: None (Open Label)
measure: DTG Ctau
time frame: 11-14 days
description: Steady-state plasma Ctau for dolutegravir
measure: RPV Ctau
time frame: 11-14 days
description: Steady-state plasma Ctau for rilpivirine
measure: Safety of DTG and RPV
time frame: 26-30 days
description: The attributable adverse events associated with use of DTG and RPV will be assessed during the study.
measure: DTG and RPV AUC
time frame: 11-14 days
description: Steady-state plasma AUC for dolutegravir and rilpivirine
measure: DTG and RPV Cmax
time frame: 11-14 days
description: Steady-stage plasma Cmax for dolutegravir and rilpivirine
arm group label: Hemodialysis Group
arm group type: Experimental
description: Receipt of JULUCA one pill per day up to 14 days
arm group label: Normal Renal Function Group
arm group type: Active Comparator
description: Receipt of JULUCA one pill per day up to 14 days
intervention type: Drug
intervention name: JULUCA 50Mg-25Mg Tablet
description: One dose of JULUCA will be taken daily for up to 14 days
arm group label: Hemodialysis Group
arm group label: Normal Renal Function Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Samir K Gupta, MD
role: Principal Investigator
affiliation: Indiana University School of Medicine
last name: Samir K Gupta, MD
phone: 317-274-7926
email: sgupta1@iu.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: Samir K. Gupta, MD
investigator title: Professor of Medicine
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Dolutegravir, rilpivirine drug combination
sharing ipd: Yes
ipd description: All IPD will provided upon request and approval by the investigators or through online data repositories such as Figshare.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: IPD will become available after publication of the data, anticipated to be by July 2022.
ipd access criteria: Fully available when posted to online repositories. Additional data upon request and approval by the study investigators. The financial sponsor will not have a role in this process.
provided document: 
provided document: 