<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/NCT02191657</url>
  </required_header>
  <id_info>
    <org_study_id>LA26-106</org_study_id>
    <nct_id>NCT02191657</nct_id>
  </id_info>
  <brief_title>Antiretroviral Activity and Pharmacokinetics of Deferiprone in Healthy Volunteers and Asymptomatic HIV-infected Subjects</brief_title>
  <official_title>A Double Blind, Placebo-controlled, Dose-escalating, Multiple Dose Study, Investigating the Safety, Antiretroviral Activity, Tolerability and Pharmacokinetic Profile of Deferiprone When Administered in Healthy Volunteers and Asymptomatic HIV Infected Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ApoPharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ApoPharma</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study was to examine the safety, efficacy, and pharmacokinetics of&#xD;
      different dosages of deferiprone in subjects with or without HIV infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Three cohorts were enrolled: two of individuals who were asymptomatically infected with HIV&#xD;
      and one of healthy volunteers. Dosages were as follows:&#xD;
&#xD;
        -  Cohort 1 (asymptomatic HIV infected subjects): 33 mg/kg deferiprone three times daily&#xD;
           for a total of 99 mg/kg/day&#xD;
&#xD;
        -  Cohort 2 (healthy volunteers): 50 mg/kg deferiprone three times daily for a total of 150&#xD;
           mg/kg/day&#xD;
&#xD;
        -  Cohort 3 (asymptomatic HIV infected subjects): 50 mg/kg deferiprone three times daily&#xD;
           for a total of 150 mg/kg/day&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2006</start_date>
  <completion_date type="Actual">April 2010</completion_date>
  <primary_completion_date type="Actual">May 2008</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>Parallel Assignment</intervention_model>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of adverse events following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers</measure>
    <time_frame>9 weeks (from receipt of first dose until 8 weeks after the last dose)</time_frame>
    <description>Collection of adverse events, including abnormal findings in physical examination, vital signs, 12-lead ECG, 24-hour Holter ECG, and laboratory variables (hematology, clinical chemistry, and urinalysis)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of viral load following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers</measure>
    <time_frame>9 weeks (pre-dose until 8 weeks after last dose)</time_frame>
    <description>Measurement of HIV RNA load for the assessment of antiretroviral activity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cluster of differentiation 4 (CD4) count and p24 antigen status following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers</measure>
    <time_frame>1 week (pre-dose to day of last dose)</time_frame>
    <description>Measurement of CD4 count and p24 antigen status for assessment of antiviral activity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax of deferiprone and deferiprone 3-O-glucuronide</measure>
    <time_frame>24-hour interval</time_frame>
    <description>Determination of Cmax following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of deferiprone and deferiprone 3-O-glucuronide</measure>
    <time_frame>24-hour interval</time_frame>
    <description>Determination of Tmax of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) 0-infinity of deferiprone and deferiprone 3-O-glucuronide</measure>
    <time_frame>24-hour interval</time_frame>
    <description>Determination of AUC 0-infinity of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2 of deferiprone and deferiprone 3-O-glucuronide</measure>
    <time_frame>24-hour interval</time_frame>
    <description>Determination of T1/2 of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>HIV Infection</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm were asymptomatic HIV-infected individuals who received a dose of 33 mg/kg deferiprone three times a day for a total daily dosage of 99 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm were healthy volunteers who received a dose of 50 mg/kg deferiprone three times a day for a total daily dosage of 150 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm were asymptomatic HIV-infected individuals who received a dose of 50 mg/kg deferiprone three times a day for a total daily dosage of 150 mg/kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Deferiprone</intervention_name>
    <description>Oral iron chelator</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <other_name>Ferriprox</other_name>
    <other_name>L1</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female aged ≥18 years and ≤ 60 years.&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) of &gt;1000/mm3 for African black population and ≥&#xD;
             1600/mm3 for all other races.&#xD;
&#xD;
          -  For Cohort 2: HIV-negative&#xD;
&#xD;
          -  For Cohorts 1 and 3: HIV-1 positive; CD4 count of at least 300/mm3; HIV-1 RNA copies&#xD;
             (viral load) &gt;10 000 copies/mL serum; and current physical health stable and not&#xD;
             requiring antiretroviral treatment&#xD;
&#xD;
          -  For Cohorts 1 and 3: Chest x-ray showing absence of active infectious diseases (such&#xD;
             as tuberculosis, viral or atypical bacteria or parasitic infection).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of any severe concomitant disease.&#xD;
&#xD;
          -  History of or current, recurrent or recent (4 weeks) febrile disease.&#xD;
&#xD;
          -  History of opportunistic infections, neoplasm or AIDS-defining conditions.&#xD;
&#xD;
          -  Inability to discontinue any medication from screening onwards, or for at least 2&#xD;
             weeks before the first admission; in particular any antiviral or therapy with&#xD;
             immunosuppressive activity.&#xD;
&#xD;
          -  Significant liver impairment: aspartate aminotransferase (AST), alanine&#xD;
             aminotransferase (ALT) ≥ 2.5 times the upper normal limit.&#xD;
&#xD;
          -  Significant kidney impairment: serum creatinine ≥ two times the upper normal limit.&#xD;
&#xD;
          -  Any concomitant disorder or resultant therapy likely to have interfered with subject&#xD;
             compliance or with study procedures.&#xD;
&#xD;
          -  Known hypersensitivity to any of the test materials or related compounds.&#xD;
&#xD;
          -  Positive test for Hepatitis B and/or C antibodies.&#xD;
&#xD;
          -  A history of multiple and/or severe allergies to drugs or foods or a history of&#xD;
             anaphylactic reactions.&#xD;
&#xD;
          -  History of seizures or epilepsy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dewald Steyn, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of the Free State, South Africa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PAREXEL International</name>
      <address>
        <city>Bloemfontein,</city>
        <zip>9324</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>November 2007</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>July 14, 2014</last_update_submitted>
  <last_update_submitted_qc>July 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>deferiprone</keyword>
  <keyword>iron chelation</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>Deferiprone</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/NCT02191657
org study id: LA26-106
nct id: NCT02191657
lead sponsor: 
has dmc: Yes
The purpose of this study was to examine the safety, efficacy, and pharmacokinetics of
      different dosages of deferiprone in subjects with or without HIV infection.
Three cohorts were enrolled: two of individuals who were asymptomatically infected with HIV
      and one of healthy volunteers. Dosages were as follows:

        -  Cohort 1 (asymptomatic HIV infected subjects): 33 mg/kg deferiprone three times daily
           for a total of 99 mg/kg/day

        -  Cohort 2 (healthy volunteers): 50 mg/kg deferiprone three times daily for a total of 150
           mg/kg/day

        -  Cohort 3 (asymptomatic HIV infected subjects): 50 mg/kg deferiprone three times daily
           for a total of 150 mg/kg/day
allocation: Randomized
intervention model: Parallel Assignment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Occurrence of adverse events following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
time frame: 9 weeks (from receipt of first dose until 8 weeks after the last dose)
description: Collection of adverse events, including abnormal findings in physical examination, vital signs, 12-lead ECG, 24-hour Holter ECG, and laboratory variables (hematology, clinical chemistry, and urinalysis)
measure: Measurement of viral load following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
time frame: 9 weeks (pre-dose until 8 weeks after last dose)
description: Measurement of HIV RNA load for the assessment of antiretroviral activity
measure: Cluster of differentiation 4 (CD4) count and p24 antigen status following repeated oral doses of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
time frame: 1 week (pre-dose to day of last dose)
description: Measurement of CD4 count and p24 antigen status for assessment of antiviral activity
measure: Cmax of deferiprone and deferiprone 3-O-glucuronide
time frame: 24-hour interval
description: Determination of Cmax following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
measure: Tmax of deferiprone and deferiprone 3-O-glucuronide
time frame: 24-hour interval
description: Determination of Tmax of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
measure: Area under the curve (AUC) 0-infinity of deferiprone and deferiprone 3-O-glucuronide
time frame: 24-hour interval
description: Determination of AUC 0-infinity of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
measure: T1/2 of deferiprone and deferiprone 3-O-glucuronide
time frame: 24-hour interval
description: Determination of T1/2 of deferiprone and its metabolite following a dose of deferiprone in asymptomatic HIV-infected subjects and healthy volunteers
arm group label: Cohort 1
arm group type: Experimental
description: Subjects in this arm were asymptomatic HIV-infected individuals who received a dose of 33 mg/kg deferiprone three times a day for a total daily dosage of 99 mg/kg
arm group label: Cohort 2
arm group type: Experimental
description: Subjects in this arm were healthy volunteers who received a dose of 50 mg/kg deferiprone three times a day for a total daily dosage of 150 mg/kg
arm group label: Cohort 3
arm group type: Experimental
description: Subjects in this arm were asymptomatic HIV-infected individuals who received a dose of 50 mg/kg deferiprone three times a day for a total daily dosage of 150 mg/kg.
intervention type: Drug
intervention name: Deferiprone
description: Oral iron chelator
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
other name: Ferriprox
other name: L1
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Dewald Steyn, MD
role: Principal Investigator
affiliation: University of the Free State, South Africa
facility: 
country: South Africa
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Deferiprone