<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/NCT03000517</url>
  </required_header>
  <id_info>
    <org_study_id>LFX/V0.1</org_study_id>
    <nct_id>NCT03000517</nct_id>
  </id_info>
  <brief_title>PK of Levofloxacin in MDR-TB Patients</brief_title>
  <official_title>Pharmacokinetics of Levofloxacin in MDR-TB Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Center Groningen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The emergence and spread of multi-drug resistant and extensively-drug resistant strains of&#xD;
      Mycobacterium tuberculosis (MDR/XDR-TB) have posed a great threat to global TB control and&#xD;
      elimination, limiting treatment success rate at worrisome 50% for MDR-TB. Among various&#xD;
      factors contributing to the development of drug resistance, low drug exposure is well&#xD;
      recognized. To overcome this, either new drugs have to be developed or the dose of currently&#xD;
      used therapy be optimized, or both. Fluoroquinolones (levofloxacin and moxifloxacin) and&#xD;
      aminoglycosides are important drugs in the MDR-TB treatment regimen. Development of acquired&#xD;
      drug resistance to these drugs could complicate and narrow down the available options, and&#xD;
      further exacerbate to pre-XDR and XDR-TB.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The main objective of this prospective clinical study is to understand the pharmacokinetics&#xD;
      of levofloxacin in MDR-TB patients, receiving standard dosage (750-1250mg) based on the body&#xD;
      weight and correlate drug exposure, with treatment outcomes.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      A prospective pharmacokinetic study&#xD;
&#xD;
      Study population: 20 MDR-TB patients&#xD;
&#xD;
      Intervention: Patients receive once daily oral dosing of levofloxacin (750-1250mg) based on&#xD;
      the body weight, under MDR-TB treatment regimen of Nepal.&#xD;
&#xD;
      Main study parameters/end points:&#xD;
&#xD;
      The pharmacokinetic parameters(Vd, CL, AUC etc.) of levofloxacin are the primary end points&#xD;
      of the study. The Cmax/MIC and AUC0-24h/MIC ratios are the best predictive parameters for&#xD;
      efficacy of levofloxacin treatment and will be estimated. Pharmacokinetics will be evaluated&#xD;
      in plasma and in oral fluid&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 4, 2016</start_date>
  <completion_date type="Actual">January 24, 2018</completion_date>
  <primary_completion_date type="Actual">October 27, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>AUC</measure>
    <time_frame>Period I (15-30) day and Period II (45-60) day</time_frame>
    <description>The main objective of this prospective clinical trial is to evaluate the levofloxacin exposures (AUC) of a standard dose (750-1250mg) in plasma and saliva of MDR-TB patients.</description>
  </primary_outcome>
  <enrollment type="Actual">20</enrollment>
  <condition>Multi-drug Resistant Tuberculosis</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma and saliva samples of MDR-TB patients on 0 hr premedication and 1,2,4,8 hrs post&#xD;
      mediation.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patient with previously treated or newly diagnosed MDR-TB who are at the end of first&#xD;
        month(15-30th day) and second month (45-60th day) of their treatment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient with TB, with Mycobacterium tuberculosis by culture/ Gene Xpert&#xD;
&#xD;
          -  Patient is 18 years or older with newly diagnosed or previously treated MDR-TB&#xD;
&#xD;
          -  Patient with sputum smear positive for acid-fast bacilli or sputum smear negative but&#xD;
             Gene Xpert (MTB/RIF) positive, and resistant to both isoniazid and rifampicin&#xD;
&#xD;
          -  Patients with MDR-TB receiving levofloxacin as a part of MDR-TB regimen&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with neurologic or severe extra-pulmonary manifestations of tuberculosis&#xD;
&#xD;
          -  Pregnant women or breast feeding mothers with MDR-TB&#xD;
&#xD;
          -  Patients with diminished renal functions or on medications for the treatment of renal&#xD;
             disorders&#xD;
&#xD;
          -  Body weight &lt;35 kg&#xD;
&#xD;
          -  Patients treated with aluminium- and magnesium containing antacids and ferrous&#xD;
             sulphates, cimetidine and probenecid, theophylline, warfarin, zidovudine, digoxin or&#xD;
             cyclosporine.&#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>Jan-Willem Alffenaar</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Groningen, University of Groningen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>German Nepal Tuberculosis Project Clinic (GENETUP)</name>
      <address>
        <city>Kalimati</city>
        <state>Kathmandu</state>
        <zip>1494</zip>
        <country>Nepal</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Nepal</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>January 24, 2018</last_update_submitted>
  <last_update_submitted_qc>January 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Groningen</investigator_affiliation>
    <investigator_full_name>Jan-Willem C Alffenaar</investigator_full_name>
    <investigator_title>PhD PharmD Clinical Pharmacologist</investigator_title>
  </responsible_party>
  <keyword>levofloxacin</keyword>
  <keyword>multi-drug resistant TB</keyword>
  <keyword>pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Tuberculosis, Multidrug-Resistant</mesh_term>
  </condition_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/NCT03000517
org study id: LFX/V0.1
nct id: NCT03000517
lead sponsor: 
has dmc: No
The emergence and spread of multi-drug resistant and extensively-drug resistant strains of
      Mycobacterium tuberculosis (MDR/XDR-TB) have posed a great threat to global TB control and
      elimination, limiting treatment success rate at worrisome 50% for MDR-TB. Among various
      factors contributing to the development of drug resistance, low drug exposure is well
      recognized. To overcome this, either new drugs have to be developed or the dose of currently
      used therapy be optimized, or both. Fluoroquinolones (levofloxacin and moxifloxacin) and
      aminoglycosides are important drugs in the MDR-TB treatment regimen. Development of acquired
      drug resistance to these drugs could complicate and narrow down the available options, and
      further exacerbate to pre-XDR and XDR-TB.

      Objective:

      The main objective of this prospective clinical study is to understand the pharmacokinetics
      of levofloxacin in MDR-TB patients, receiving standard dosage (750-1250mg) based on the body
      weight and correlate drug exposure, with treatment outcomes.

      Study design:

      A prospective pharmacokinetic study

      Study population: 20 MDR-TB patients

      Intervention: Patients receive once daily oral dosing of levofloxacin (750-1250mg) based on
      the body weight, under MDR-TB treatment regimen of Nepal.

      Main study parameters/end points:

      The pharmacokinetic parameters(Vd, CL, AUC etc.) of levofloxacin are the primary end points
      of the study. The Cmax/MIC and AUC0-24h/MIC ratios are the best predictive parameters for
      efficacy of levofloxacin treatment and will be estimated. Pharmacokinetics will be evaluated
      in plasma and in oral fluid
observational model: Cohort
time perspective: Prospective
measure: AUC
time frame: Period I (15-30) day and Period II (45-60) day
description: The main objective of this prospective clinical trial is to evaluate the levofloxacin exposures (AUC) of a standard dose (750-1250mg) in plasma and saliva of MDR-TB patients.
Plasma and saliva samples of MDR-TB patients on 0 hr premedication and 1,2,4,8 hrs post
      mediation.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jan-Willem Alffenaar
role: Principal Investigator
affiliation: University Medical Center Groningen, University of Groningen
facility: 
country: Nepal
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Groningen
investigator full name: Jan-Willem C Alffenaar
investigator title: PhD PharmD Clinical Pharmacologist
mesh term: Tuberculosis
mesh term: Tuberculosis, Multidrug-Resistant