<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/NCT01671982</url>
  </required_header>
  <id_info>
    <org_study_id>ALTER</org_study_id>
    <nct_id>NCT01671982</nct_id>
  </id_info>
  <brief_title>ALternative TEnofovir Dosing in Adults With Moderate Renal Function Impairment</brief_title>
  <acronym>ALTER</acronym>
  <official_title>Tenofovir Pharmacokinetics in HIV-infected Thai Adults With Moderate Renal Function Impairment Receiving Either a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based or Lopinavir/Ritonavir-based Antiretroviral Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut de Recherche pour le Developpement</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Government Pharmaceutical Organization</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chiang Mai University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut de Recherche pour le Developpement</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the drug concentrations of tenofovir (TDF) in HIV-infected Thai adults with&#xD;
      moderate renal function impairment when administered at the recommended dose of 300 mg every&#xD;
      48 hours, and at an alternative dose of 150 mg every 24 hours.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is designed as a Phase I, non-randomized, open-label, pharmacokinetic study. We&#xD;
      hypothesize that administration of tenofovir 150 mg once daily to HIV-infected Thai adults&#xD;
      with moderate renal function impairment (CLcr between 30 to &lt;50 mL/min) will provide&#xD;
      comparable drug exposure to the current recommended dose of 300 mg every 48 hours.&#xD;
&#xD;
      Confirmed HIV-positive subjects receiving tenofovir (TDF) 300 mg, every 48 hours, as part of&#xD;
      an NNRTI-based or lopinavir/ritonavir (LPV/r)-based HAART regimen will be proposed to&#xD;
      participate.&#xD;
&#xD;
      Subjects meeting the required criteria will be enrolled into one of 2 groups depending on&#xD;
      their HAART regimen: .&#xD;
&#xD;
      Group 1: Subjects receiving tenofovir 300 mg, every 48 hours, in combination with lamivudine&#xD;
      and an NNRTI,and a confirmed CLcr 30 to &lt;50 mL/min&#xD;
&#xD;
      Group 2: Subjects receiving tenofovir 300 mg, every 48 hours, in combination with lamivudine&#xD;
      and lopinavir/ritonavir, and a confirmed CLcr 30 to &lt;50 mL/min&#xD;
&#xD;
      The study procedures are identical for both groups. All subjects enrolled will have two study&#xD;
      visits. At the first visit, a 48-hour pharmacokinetic evaluation will be performed.&#xD;
      Immediately following completion of the PK sampling, the tenofovir dose will be changed to&#xD;
      150 mg, once daily. Two weeks later, at the second visit, a 24-hour pharmacokinetic&#xD;
      evaluation will be performed. Following completion of the second PK sampling the tenofovir&#xD;
      dose will be changed back to 300 mg every 48 hours. At this time the subjects has reach the&#xD;
      end of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">January 2014</primary_completion_date>
  <phase>Phase 1</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>Tenofovir plasma area-under the concentration time curve (AUC)</measure>
    <time_frame>Study Entry and Day 14</time_frame>
    <description>For each patient, ratios of AUC0-last of q24h versus q48h will be calculated. Geometric mean ratios (GMRs) with 90% CI will be calculated after log-transformation of within patient ratios.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Tenofovir-containing HAART</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Tenofovir Dose Adjustment</intervention_name>
    <description>In subjects with a confirmed CLcr 30 to &lt;50 mL/min, switch tenofovir 300 mg every 48 hours, to 150 mg once daily for 2 weeks.</description>
    <arm_group_label>Tenofovir-containing HAART</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt;18 years old&#xD;
&#xD;
          -  provided written informed consent&#xD;
&#xD;
          -  receiving the tenofovir tablet formulation from the Thai Government Pharmaceutical&#xD;
             Organization (GPO) for at least 4 weeks before enrollment&#xD;
&#xD;
          -  documentation of confirmed HIV-1 infection (documented by two serology tests obtained&#xD;
             at two different dates)&#xD;
&#xD;
          -  Confirmed Creatinine clearance result between 30 to &lt;50 mL/min [confirmed defined as&#xD;
             two CLcr determinations calculated using the Cockcroft-Gault equation within two weeks&#xD;
             of each other, within 1 month prior to entry]&#xD;
&#xD;
          -  received tenofovir 300 mg, every 48 hours for at least 2 weeks prior to entry, in&#xD;
             combination with 3TC plus NNRTI, or 3TC plus lopinavir/ritonavir&#xD;
&#xD;
          -  a HIV-1 RNA viral load &lt; 50 copies/mL within 6 months prior to entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant use of a atazanavir, didanosine&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  Any of the following laboratory tests within 30 days prior to study entry classified&#xD;
             as ≥ Grade 3 (see DAIDS Table for Grading the Severity of Adult and Pediatric Adverse&#xD;
             Events, Version 1.0 [Dec. 2004], Clarification August, 2009): neutrophil count,&#xD;
             hemoglobin, platelets, AST, or ALT&#xD;
&#xD;
          -  HBs-antigen positive&#xD;
&#xD;
          -  Any clinically significant diseases (other than HIV-1 infection) or clinically&#xD;
             significant findings during the screening medical history or physical examination&#xD;
             that, in the investigator's opinion, would compromise participation in this study&#xD;
&#xD;
          -  concurrent participation to any other clinical trial without prior agreement of the&#xD;
             two study teams&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim R Cressey, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>PHPT / Chiang Mai University / IRD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sanpatong Hospital</name>
      <address>
        <city>Sanpatong</city>
        <state>Chiang Mai</state>
        <zip>20120</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HIV-NAT</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nakornping Hospital</name>
      <address>
        <city>Chiang Mai</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chonburi Hospital</name>
      <address>
        <city>Chonburi</city>
        <zip>20000</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Phayao Hospital</name>
      <address>
        <city>Phayao</city>
        <zip>56000</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <link>
    <url>http://www.phpt.org</url>
    <description>Related Info</description>
  </link>
  <results_reference>
    <citation>Cressey TR, Avihingsanon A, Halue G, Leenasirimakul P, Sukrakanchana PO, Tawon Y, Jaisieng N, Jourdain G, Podany AT, Fletcher CV, Klinbuayaem V, Bowonwatanuwong C. Plasma and Intracellular Pharmacokinetics of Tenofovir Disoproxil Fumarate 300 mg Every 48 Hours vs 150 mg Once Daily in HIV-Infected Adults With Moderate Renal Function Impairment. Clin Infect Dis. 2015 Aug 15;61(4):633-9. doi: 10.1093/cid/civ346. Epub 2015 Apr 28.</citation>
    <PMID>25921689</PMID>
  </results_reference>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>August 17, 2012</study_first_submitted>
  <study_first_submitted_qc>August 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</study_first_posted>
  <last_update_submitted>May 28, 2015</last_update_submitted>
  <last_update_submitted_qc>May 28, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 29, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institut de Recherche pour le Developpement</investigator_affiliation>
    <investigator_full_name>Gonzague Jourdain</investigator_full_name>
    <investigator_title>Director, International Reserach Unit 174</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</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/NCT01671982
org study id: ALTER
nct id: NCT01671982
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
To assess the drug concentrations of tenofovir (TDF) in HIV-infected Thai adults with
      moderate renal function impairment when administered at the recommended dose of 300 mg every
      48 hours, and at an alternative dose of 150 mg every 24 hours.
The study is designed as a Phase I, non-randomized, open-label, pharmacokinetic study. We
      hypothesize that administration of tenofovir 150 mg once daily to HIV-infected Thai adults
      with moderate renal function impairment (CLcr between 30 to <50 mL/min) will provide
      comparable drug exposure to the current recommended dose of 300 mg every 48 hours.

      Confirmed HIV-positive subjects receiving tenofovir (TDF) 300 mg, every 48 hours, as part of
      an NNRTI-based or lopinavir/ritonavir (LPV/r)-based HAART regimen will be proposed to
      participate.

      Subjects meeting the required criteria will be enrolled into one of 2 groups depending on
      their HAART regimen: .

      Group 1: Subjects receiving tenofovir 300 mg, every 48 hours, in combination with lamivudine
      and an NNRTI,and a confirmed CLcr 30 to <50 mL/min

      Group 2: Subjects receiving tenofovir 300 mg, every 48 hours, in combination with lamivudine
      and lopinavir/ritonavir, and a confirmed CLcr 30 to <50 mL/min

      The study procedures are identical for both groups. All subjects enrolled will have two study
      visits. At the first visit, a 48-hour pharmacokinetic evaluation will be performed.
      Immediately following completion of the PK sampling, the tenofovir dose will be changed to
      150 mg, once daily. Two weeks later, at the second visit, a 24-hour pharmacokinetic
      evaluation will be performed. Following completion of the second PK sampling the tenofovir
      dose will be changed back to 300 mg every 48 hours. At this time the subjects has reach the
      end of the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Tenofovir plasma area-under the concentration time curve (AUC)
time frame: Study Entry and Day 14
description: For each patient, ratios of AUC0-last of q24h versus q48h will be calculated. Geometric mean ratios (GMRs) with 90% CI will be calculated after log-transformation of within patient ratios.
arm group label: Tenofovir-containing HAART
arm group type: Experimental
intervention type: Other
intervention name: Tenofovir Dose Adjustment
description: In subjects with a confirmed CLcr 30 to <50 mL/min, switch tenofovir 300 mg every 48 hours, to 150 mg once daily for 2 weeks.
arm group label: Tenofovir-containing HAART
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tim R Cressey, PhD
role: Principal Investigator
affiliation: PHPT / Chiang Mai University / IRD
facility: 
facility: 
facility: 
facility: 
facility: 
country: Thailand
url: http://www.phpt.org
description: Related Info
citation: Cressey TR, Avihingsanon A, Halue G, Leenasirimakul P, Sukrakanchana PO, Tawon Y, Jaisieng N, Jourdain G, Podany AT, Fletcher CV, Klinbuayaem V, Bowonwatanuwong C. Plasma and Intracellular Pharmacokinetics of Tenofovir Disoproxil Fumarate 300 mg Every 48 Hours vs 150 mg Once Daily in HIV-Infected Adults With Moderate Renal Function Impairment. Clin Infect Dis. 2015 Aug 15;61(4):633-9. doi: 10.1093/cid/civ346. Epub 2015 Apr 28.
PMID: 25921689
responsible party type: Principal Investigator
investigator affiliation: Institut de Recherche pour le Developpement
investigator full name: Gonzague Jourdain
investigator title: Director, International Reserach Unit 174
mesh term: Tenofovir