<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/NCT01730664</url>
  </required_header>
  <id_info>
    <org_study_id>ETB/V0.2</org_study_id>
    <nct_id>NCT01730664</nct_id>
  </id_info>
  <brief_title>PK/PD of Ertapenem In Patients With TB</brief_title>
  <official_title>Pharmacokinetics and Pharmacodynamics of Ertapenem in Patients With Tuberculosis</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale:&#xD;
&#xD;
      Treatment of multidrug or extensively drug resistant tuberculosis (MDR/XDR-TB) is a real&#xD;
      challenge as failure in response to treatment and serious side-effects are frequently&#xD;
      encountered. New, more effective drugs with less side effects are therefore urgently needed&#xD;
      to solve this problem. Although several new drugs against TB are in the pipeline, physicians&#xD;
      currently have limited treatment options for treatment of complicated MDR/XDR-TB cases.&#xD;
      Therefore, drugs developed and labeled for other infectious diseases are evaluated for TB.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The main objective of this prospective clinical trial is to evaluate pharmacokinetics of a&#xD;
      standard dose (2000mg) of ertapenem in TB patients. This clinical trial will provide&#xD;
      important information on PK of ertapenem in TB patients for future studies. Data can be used&#xD;
      for limited sampling strategies for ertapenem based on a pharmacokinetic population model&#xD;
      constructed from the full PK curves of the patients.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      A prospective pharmacokinetic study.&#xD;
&#xD;
      Study population: 12 TB patients.&#xD;
&#xD;
      Intervention: Single dose of 2000mg in a 30 minutes intravenous infusion.&#xD;
&#xD;
      Main study parameters/endpoints:&#xD;
&#xD;
      The pharmacokinetic parameters (Vd, Cl, AUC, etc) of ertapenem are the primary endpoints of&#xD;
      the study. The T&gt;MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio are most&#xD;
      likely the best predictive parameters for efficacy of ertapenem treatment and will be&#xD;
      calculated for a range of M tuberculosis isolates.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 26, 2017</start_date>
  <completion_date type="Actual">July 13, 2017</completion_date>
  <primary_completion_date type="Actual">July 13, 2017</primary_completion_date>
  <phase>Phase 2</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC</measure>
    <time_frame>first day</time_frame>
    <description>main objective of this prospective clinical trial is to evaluate AUC of a standard dose (1000mg) of ertapenem in TB patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety: number of patients with organ dysfunction</measure>
    <time_frame>day 1 and day 3</time_frame>
    <description>renal function(eGFR) and liver enzymes(ALAT; ASAT)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>limited sampling strategies</measure>
    <time_frame>day 1</time_frame>
    <description>limited sampling strategies for ertapenem based on a pharmacokinetic population model constructed from the full PK curves of the patients.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>PK of Ertapenem in TB Patients</condition>
  <arm_group>
    <arm_group_label>ertapenem</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single dose ertapenem</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ertapenem</intervention_name>
    <description>single dose of 2000mg ertapenem IV</description>
    <arm_group_label>ertapenem</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with TB, with Mycobacterium tuberculosis (or M. africanum) by culture and /&#xD;
             or molecular test&#xD;
&#xD;
          -  Adults: from 18 years until 64 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -Contra-indications for ertapenem:&#xD;
&#xD;
          -  There are few adverse effects of ertapenem. The only absolute contra- indication is a&#xD;
             previous anaphylactic reaction to ertapenem or other β-lactam antibiotic.&#xD;
&#xD;
          -  Renal Insufficiency, defined by a eGFR of 30ml/min&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  HIV&#xD;
&#xD;
          -  Body weight &lt; 40 kg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UMCG - Tuberculosis Center</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Tremblay LW, Fan F, Blanchard JS. Biochemical and structural characterization of Mycobacterium tuberculosis beta-lactamase with the carbapenems ertapenem and doripenem. Biochemistry. 2010 May 4;49(17):3766-73. doi: 10.1021/bi100232q.</citation>
    <PMID>20353175</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>August 24, 2017</last_update_submitted>
  <last_update_submitted_qc>August 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2017</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>ertapenem</keyword>
  <keyword>tuberculosis</keyword>
  <keyword>pharmacokinetics</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>Ertapenem</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/NCT01730664
org study id: ETB/V0.2
nct id: NCT01730664
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Rationale:

      Treatment of multidrug or extensively drug resistant tuberculosis (MDR/XDR-TB) is a real
      challenge as failure in response to treatment and serious side-effects are frequently
      encountered. New, more effective drugs with less side effects are therefore urgently needed
      to solve this problem. Although several new drugs against TB are in the pipeline, physicians
      currently have limited treatment options for treatment of complicated MDR/XDR-TB cases.
      Therefore, drugs developed and labeled for other infectious diseases are evaluated for TB.

      Objective:

      The main objective of this prospective clinical trial is to evaluate pharmacokinetics of a
      standard dose (2000mg) of ertapenem in TB patients. This clinical trial will provide
      important information on PK of ertapenem in TB patients for future studies. Data can be used
      for limited sampling strategies for ertapenem based on a pharmacokinetic population model
      constructed from the full PK curves of the patients.

      Study design:

      A prospective pharmacokinetic study.

      Study population: 12 TB patients.

      Intervention: Single dose of 2000mg in a 30 minutes intravenous infusion.

      Main study parameters/endpoints:

      The pharmacokinetic parameters (Vd, Cl, AUC, etc) of ertapenem are the primary endpoints of
      the study. The T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio are most
      likely the best predictive parameters for efficacy of ertapenem treatment and will be
      calculated for a range of M tuberculosis isolates.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: AUC
time frame: first day
description: main objective of this prospective clinical trial is to evaluate AUC of a standard dose (1000mg) of ertapenem in TB patients
measure: Safety: number of patients with organ dysfunction
time frame: day 1 and day 3
description: renal function(eGFR) and liver enzymes(ALAT; ASAT)
measure: limited sampling strategies
time frame: day 1
description: limited sampling strategies for ertapenem based on a pharmacokinetic population model constructed from the full PK curves of the patients.
arm group label: ertapenem
arm group type: Experimental
description: single dose ertapenem
intervention type: Drug
intervention name: ertapenem
description: single dose of 2000mg ertapenem IV
arm group label: ertapenem
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
facility: 
country: Netherlands
citation: Tremblay LW, Fan F, Blanchard JS. Biochemical and structural characterization of Mycobacterium tuberculosis beta-lactamase with the carbapenems ertapenem and doripenem. Biochemistry. 2010 May 4;49(17):3766-73. doi: 10.1021/bi100232q.
PMID: 20353175
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: Ertapenem