<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/NCT01700790</url>
  </required_header>
  <id_info>
    <org_study_id>20100325</org_study_id>
    <nct_id>NCT01700790</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin</brief_title>
  <official_title>A Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir in Combination With Rifampin in HIV-1-infected Patients With Tuberculosis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Miami</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oswaldo Cruz Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The object of this study is to evaluate the pharmacokinetic interactions, short term safety&#xD;
      and efficacy of standard dose lopinavir/ritonavir 200mg/50 (two tablets twice daily) given&#xD;
      with ritonavir 100 mg three tablets twice daily given in combination with rifampin in&#xD;
      HIV-infected persons with tuberculosis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be an open label non-randomized pharmacokinetic study of 10-12 HIV-infected&#xD;
      patients co-infected with Mycobacterium tuberculosis.&#xD;
&#xD;
      Enrollment: Potential subjects with active tuberculosis who have tolerated a rifampin&#xD;
      containing regimen for at least 2 weeks. Potential subjects will be referred from the&#xD;
      surrounding communities to Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)&#xD;
&#xD;
      Visit 1: Subjects will then be started on lopinavir/ritonavir containing HAART regimen with&#xD;
      standard twice daily dosing. Ritonavir 100 mg capsules will be added to the regimen and the&#xD;
      dose escalated until the patient is taking 3 capsules twice daily. The time between&#xD;
      enrollment and visit 1 will be determined by the treating physician.&#xD;
&#xD;
      Visit 2: They will return about 1 week after dose escalation has been completed to sample&#xD;
      lopinavir and rifampin concentrations.&#xD;
&#xD;
      Visit 3: Subject will return in 2 weeks to have repeat to review results of lopinavir&#xD;
      concentrations and response to therapy. Ritonavir will be adjusted as needed.&#xD;
&#xD;
      Visit 4: Subject will then return in 4 weeks for last visit for evaluation. Lopinavir and&#xD;
      rifampin PK will be done.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    No Further Funding&#xD;
  </why_stopped>
  <start_date type="Actual">February 2016</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">November 17, 2018</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>Proportion of patients with expected pre dose concentration of lopinavir.</measure>
    <time_frame>Weeks 2 and 8: lopinavir time points at hours 0, 2, 4, 6 and 8.</time_frame>
    <description>The expected pre dose concentration of lopinavir is &gt;1.0 mcg/mL.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with successful treatment of HIV therapy.</measure>
    <time_frame>Approximately 10-12 weeks</time_frame>
    <description>HIV failure will be defined as failure to drop the viral load by 0.5 log 10 copies/mL drop by week 4 of treatment and a viral load drop &gt;1 log 10 copies/ml by week 8.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with expected AUC of rifampin</measure>
    <time_frame>Approximatley 10-12 weeks</time_frame>
    <description>The expected AUC of rifampin is 44-70 mcg•h/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patient with success of tuberculosis therapy</measure>
    <time_frame>Approximatly 10-12 weeks</time_frame>
    <description>Success of treatment using criteria established by the Brazilian National Ttuberculosis Program.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with expected Cmax and AUC of lopinavir</measure>
    <time_frame>10-12 weeks</time_frame>
    <description>The expected Cmax of lopinavir is 6-14 mcg/mL. The expected AUC lopinavir is 56-130 µg•h/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with expected Cmax of rifampin.</measure>
    <time_frame>Weeks 2 and 8: rifampin time points at hours 0, 2, 4, 6 and 8.</time_frame>
    <description>Expected maximum concentration of rifampin is 8-24 mcg/mL</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>AIDS</condition>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>Lopinavir/ritonavir and ritonavir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two tablets of twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 tablets of ritonavir 100 mg of twice daily given with rifampin 600 mg daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lopinavir/ritonavir and ritonavir</intervention_name>
    <description>Two tablets twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 capsules of ritonavir 100 mg twice daily given with rifampin 600 mg daily</description>
    <arm_group_label>Lopinavir/ritonavir and ritonavir</arm_group_label>
    <other_name>Kaletra</other_name>
    <other_name>Norvir</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  Antiretroviral naive&#xD;
&#xD;
          -  If not antiretroviral naïve they must meet the following criteria:&#xD;
&#xD;
               -  Taking Kaletra containing regimen with suppressed viral load.&#xD;
&#xD;
               -  Taking an NNRTI or integrase containing regimen without prior history of use of&#xD;
                  PI for more than 2 weeks&#xD;
&#xD;
               -  Taking an NNRTI or integrase containing regimen with prior exposure to PI greater&#xD;
                  than 2 weeks. It must be clearly stated in the source document that PI was&#xD;
                  switched to another agent for convenience.&#xD;
&#xD;
               -  Taking another PI containing regimens with suppressed viral load. It must be&#xD;
                  clearly stated in source document that if another PI was used for greater than 2&#xD;
                  weeks the regimen was switched to another agent for convenience. Subjects with&#xD;
                  prior history of PI use may be enrolled, if there is a genotype showing no&#xD;
                  resistance to Kaletra Other Inclusion criteria&#xD;
&#xD;
          -  Be at least 18 years of age and able to give informed consent.&#xD;
&#xD;
          -  Diagnosed with TB by criteria per Brazilian Ministry of Health&#xD;
&#xD;
          -  Have a good clinical response to TB.&#xD;
&#xD;
          -  Tolerating tuberculosis therapy containing rifampin for the 2 weeks prior to&#xD;
             screening,except for persons taking protease inhibitors at time of diagnosis of TB.,.&#xD;
             Subjects taking protease inhibitors will be screened and initiate visit 1 within 3&#xD;
             days of starting TB medication&#xD;
&#xD;
          -  HIV positive with documentation present in source document.&#xD;
&#xD;
          -  Have a CD4 cell count greater than 50 cells/mm3if not taking ART. Persons with cd4 &lt;&#xD;
             50 may be enrolled, if it is felt that in the best interest of the patient, that&#xD;
             enrollment in the study will allow for quicker initiation of antiretroviral therapy&#xD;
             than referral to another treatment center.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-compliance with DOTPlus. Alternatively DOT can be done by telephoning patient on a&#xD;
             daily basis 5 times a week and having patient annotate taking drug in a log which&#xD;
             would be reviewed by clinic staff&#xD;
&#xD;
          -  History of being treated for tuberculosis in the prior 2 years unless there is DST,&#xD;
             including PCR testing, showing sensitivity to rifamycin.&#xD;
&#xD;
          -  Known hypersensitivity to rifampin or rifabutin.&#xD;
&#xD;
          -  Liver enzymes greater than 2 times ULN.&#xD;
&#xD;
          -  Bilirubin greater than 2 times ULN.&#xD;
&#xD;
          -  Serum creatinine greater than 3 times ULN.&#xD;
&#xD;
          -  Hemoglobin less than 7.0 gms even if receiving erythropoietin.&#xD;
&#xD;
          -  Absolute neutrophil count less than 750 cells/mm3 even if receiving G-CSF.&#xD;
&#xD;
          -  Fasting triglycerides greater than 400 mg/dL.&#xD;
&#xD;
          -  Fasting cholesterol &gt; 1.6 upper limits of normal.&#xD;
&#xD;
          -  GI intolerance of tuberculosis medications requiring discontinuation of tuberculosis&#xD;
             medications.&#xD;
&#xD;
          -  Fasting glucose greater 150 mg/dL.&#xD;
&#xD;
          -  Pregnant women.&#xD;
&#xD;
          -  Use of one of the prohibited medications&#xD;
&#xD;
          -  Any condition that the investigators feel could compromise the use of the current&#xD;
             medication.&#xD;
&#xD;
          -  Have a CD4 cell count of 50 cells/mm3or less&#xD;
&#xD;
          -  Hepatitis B or C infection&#xD;
&#xD;
          -  Alcohol or illicit drug use, which in the investigators opinion may affect&#xD;
             participation in study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Catherine Boulanger, MD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami Miller Medical School of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Valeria Calvicanti Rolla, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oswaldo Cruz Foundation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto Nacional de Infectologia Evandro Chagas - Fiocruz(INI), Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)</name>
      <address>
        <city>Rio de Janeiro</city>
        <state>RJ</state>
        <zip>21040-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Ren Y, Nuttall JJ, Egbers C, Eley BS, Meyers TM, Smith PJ, Maartens G, McIlleron HM. Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9. doi: 10.1097/QAI.0b013e3181642257.</citation>
    <PMID>18197120</PMID>
  </reference>
  <reference>
    <citation>la Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, Boeree MJ, Koopmans PP, Hekster YA, Burger DM. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004 May;48(5):1553-60. doi: 10.1128/AAC.48.5.1553-1560.2004.</citation>
    <PMID>15105105</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>October 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <last_update_submitted>May 14, 2019</last_update_submitted>
  <last_update_submitted_qc>May 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Catherine Boulanger</investigator_full_name>
    <investigator_title>Associate of Professor of Clinical Medicine</investigator_title>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>AIDS</keyword>
  <keyword>Tuberculosis</keyword>
  <keyword>Rifampin</keyword>
  <keyword>Lopinavir</keyword>
  <keyword>Pharmacokinetic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Lopinavir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT01700790
org study id: 20100325
nct id: NCT01700790
lead sponsor: 
collaborator: 
has dmc: No
The object of this study is to evaluate the pharmacokinetic interactions, short term safety
      and efficacy of standard dose lopinavir/ritonavir 200mg/50 (two tablets twice daily) given
      with ritonavir 100 mg three tablets twice daily given in combination with rifampin in
      HIV-infected persons with tuberculosis
This will be an open label non-randomized pharmacokinetic study of 10-12 HIV-infected
      patients co-infected with Mycobacterium tuberculosis.

      Enrollment: Potential subjects with active tuberculosis who have tolerated a rifampin
      containing regimen for at least 2 weeks. Potential subjects will be referred from the
      surrounding communities to Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)

      Visit 1: Subjects will then be started on lopinavir/ritonavir containing HAART regimen with
      standard twice daily dosing. Ritonavir 100 mg capsules will be added to the regimen and the
      dose escalated until the patient is taking 3 capsules twice daily. The time between
      enrollment and visit 1 will be determined by the treating physician.

      Visit 2: They will return about 1 week after dose escalation has been completed to sample
      lopinavir and rifampin concentrations.

      Visit 3: Subject will return in 2 weeks to have repeat to review results of lopinavir
      concentrations and response to therapy. Ritonavir will be adjusted as needed.

      Visit 4: Subject will then return in 4 weeks for last visit for evaluation. Lopinavir and
      rifampin PK will be done.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients with expected pre dose concentration of lopinavir.
time frame: Weeks 2 and 8: lopinavir time points at hours 0, 2, 4, 6 and 8.
description: The expected pre dose concentration of lopinavir is >1.0 mcg/mL.
measure: Proportion of patients with successful treatment of HIV therapy.
time frame: Approximately 10-12 weeks
description: HIV failure will be defined as failure to drop the viral load by 0.5 log 10 copies/mL drop by week 4 of treatment and a viral load drop >1 log 10 copies/ml by week 8.
measure: Proportion of patients with expected AUC of rifampin
time frame: Approximatley 10-12 weeks
description: The expected AUC of rifampin is 44-70 mcg•h/mL
measure: Proportion of patient with success of tuberculosis therapy
time frame: Approximatly 10-12 weeks
description: Success of treatment using criteria established by the Brazilian National Ttuberculosis Program.
measure: Proportion of patients with expected Cmax and AUC of lopinavir
time frame: 10-12 weeks
description: The expected Cmax of lopinavir is 6-14 mcg/mL. The expected AUC lopinavir is 56-130 µg•h/mL
measure: Proportion of patients with expected Cmax of rifampin.
time frame: Weeks 2 and 8: rifampin time points at hours 0, 2, 4, 6 and 8.
description: Expected maximum concentration of rifampin is 8-24 mcg/mL
arm group label: Lopinavir/ritonavir and ritonavir
arm group type: Experimental
description: Two tablets of twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 tablets of ritonavir 100 mg of twice daily given with rifampin 600 mg daily.
intervention type: Drug
intervention name: Lopinavir/ritonavir and ritonavir
description: Two tablets twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 capsules of ritonavir 100 mg twice daily given with rifampin 600 mg daily
arm group label: Lopinavir/ritonavir and ritonavir
other name: Kaletra
other name: Norvir
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Catherine Boulanger, MD.
role: Principal Investigator
affiliation: University of Miami Miller Medical School of Medicine
last name: Valeria Calvicanti Rolla, MD
role: Principal Investigator
affiliation: Oswaldo Cruz Foundation
facility: 
country: Brazil
citation: Ren Y, Nuttall JJ, Egbers C, Eley BS, Meyers TM, Smith PJ, Maartens G, McIlleron HM. Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9. doi: 10.1097/QAI.0b013e3181642257.
PMID: 18197120
citation: la Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, Boeree MJ, Koopmans PP, Hekster YA, Burger DM. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004 May;48(5):1553-60. doi: 10.1128/AAC.48.5.1553-1560.2004.
PMID: 15105105
responsible party type: Principal Investigator
investigator affiliation: University of Miami
investigator full name: Catherine Boulanger
investigator title: Associate of Professor of Clinical Medicine
mesh term: Tuberculosis
mesh term: Ritonavir
mesh term: Lopinavir
sharing ipd: No