<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/NCT03246386</url>
  </required_header>
  <id_info>
    <org_study_id>UMCN-AKF-17.08</org_study_id>
    <nct_id>NCT03246386</nct_id>
  </id_info>
  <brief_title>Dosing Obese With Noxafil® Under a Trial (DONUT)</brief_title>
  <acronym>DONUT</acronym>
  <official_title>Pharmacokinetics of Posaconazole Given as a Single Intravenous Dose to Obese Subjects: Dosing Obese With Noxafil® Under a Trial (DONUT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>St. Antonius Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <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>
      Although posaconazole is approved for the prophylaxes and treatment of invasive fungal&#xD;
      infections, specific dosing guidelines for posaconazole in (morbidly) obese patients are not&#xD;
      specified. There is clear evidence indicating that heavier patients are receiving a&#xD;
      sub-optimal dose if the current guidelines are used. Specifically in the setting of augmented&#xD;
      prevalence of species with intermediate susceptible to posaconazole, adequate dosing is&#xD;
      needed at start of treatment.&#xD;
&#xD;
      Therefore it seems prudent to conduct a trial in a cohort of obese patients who receive&#xD;
      posaconazole (300mg or 400mg) and define the pharmacokinetics. These will then be compared to&#xD;
      the pharmacokinetics in a normal-weight group receiving 300mg posaconazole.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obese patients with a BMI ≥ 35 kg/m2 undergoing endoscopic gastric bypass surgery will&#xD;
      receive a 300 mg or 400mg dose of posaconazole. A PK curve will be determined after&#xD;
      administration at t=0.45, 0.75, 1, 1.5, 2, 4, 8, 12, 24, and (if feasible) 48 hours post&#xD;
      infusion. Blood samples (4 mL) on PK days will be taken to obtain at least 2.0 mL of plasma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2017</start_date>
  <completion_date type="Actual">September 1, 2018</completion_date>
  <primary_completion_date type="Actual">September 1, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Posaconazole exposure</measure>
    <time_frame>Through study completion (usually after 24 or 48 hours)</time_frame>
    <description>The concentration-time curve of posaconazole in obese will be compared with that in non-obese subjects. Exposure is assessed by Area-Under-the-Curve from zero to 48 hours (AUC0-48h).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exposure with augemented posaconazol dose</measure>
    <time_frame>Through study completion (usually after 24 or 48 hours)</time_frame>
    <description>The concentration-time curve of posaconazole in obese receiving 400mg will be compared with that in non-obese subjects. Exposure is assessed by Area-Under-the-Curve from zero to 48 hours (AUC0-48h).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Morbid Obesity</condition>
  <arm_group>
    <arm_group_label>Obese subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with a BMI&gt;35 kg/m2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-obese subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects with a BMI&gt;18.5 and &lt;25 kg/m2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Posaconazole Injection [Noxafil] 300mg</intervention_name>
    <description>Single dose by intravenous infusion 300mg</description>
    <arm_group_label>Non-obese subjects</arm_group_label>
    <arm_group_label>Obese subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Posaconazole Injection [Noxafil] 400mg</intervention_name>
    <description>Single dose by intravenous infusion 400mg</description>
    <arm_group_label>Obese subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects BMI:&#xD;
&#xD;
               -  obese groups: subject must have a BMI ≥35 kg/m2 at the time of inclusion,&#xD;
&#xD;
               -  non-obese group: subject must have a BMI ≥18.5 and &lt; 25kg/m2 at the time of&#xD;
                  inclusion.&#xD;
&#xD;
          2. Subject is at least 18 of age on the day of screening and not older than 65 years of&#xD;
             age on the day of dosing;&#xD;
&#xD;
          3. If a woman, is neither pregnant nor able to become pregnant and is not nursing an&#xD;
             infant;&#xD;
&#xD;
          4. Subject is able and willing to sign the Informed Consent before screening evaluations.&#xD;
&#xD;
             For the non-obese subjects the following additional inclusion criteria applies:&#xD;
&#xD;
          5. Subject is in good age-appropriate health condition as established by medical history,&#xD;
             physical examination, electrocardiography, results of biochemistry, hematology and&#xD;
             urinalysis testing within 6 weeks prior to study drug administration. Results of&#xD;
             biochemistry, hematology and urinalysis testing should be within the laboratory's&#xD;
             reference ranges (see Appendix A). If laboratory results are not within the reference&#xD;
             ranges, the subject is included based on the investigator's judgment that the observed&#xD;
             deviations are not clinically relevant. This should be clearly recorded;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Documented history of sensitivity to medicinal products or excipients similar to those&#xD;
             found in the posaconazole preparation;&#xD;
&#xD;
          2. History of, or known abuse of drugs, alcohol or solvents (up until a maximum of three&#xD;
             months before study drug administration);&#xD;
&#xD;
          3. Use of medication that has known relevant interaction with study drug as determined by&#xD;
             the investigator up to 1 weeks prior to study drug administration.&#xD;
&#xD;
          4. Donation of blood or plasma to a blood bank or in a clinical study (except a screening&#xD;
             visit) within 4 weeks prior to study drug administration;&#xD;
&#xD;
          5. Blood transfusion within 8 weeks prior to study drug administration;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roger Brüggemann, PhD-PharmD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Antonius hospital</name>
      <address>
        <city>Nieuwegein</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>https://pubmed.ncbi.nlm.nih.gov/31971567/</url>
    <description>paper</description>
  </link>
  <results_reference>
    <citation>Wasmann RE, Smit C, van Donselaar MH, van Dongen EPA, Wiezer RMJ, Verweij PE, Burger DM, Knibbe CAJ, Bruggemann RJM. Implications for IV posaconazole dosing in the era of obesity. J Antimicrob Chemother. 2020 Apr 1;75(4):1006-1013. doi: 10.1093/jac/dkz546.</citation>
    <PMID>31971567</PMID>
  </results_reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>October 16, 2020</last_update_submitted>
  <last_update_submitted_qc>October 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity, Morbid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Posaconazole</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/NCT03246386
org study id: UMCN-AKF-17.08
nct id: NCT03246386
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Although posaconazole is approved for the prophylaxes and treatment of invasive fungal
      infections, specific dosing guidelines for posaconazole in (morbidly) obese patients are not
      specified. There is clear evidence indicating that heavier patients are receiving a
      sub-optimal dose if the current guidelines are used. Specifically in the setting of augmented
      prevalence of species with intermediate susceptible to posaconazole, adequate dosing is
      needed at start of treatment.

      Therefore it seems prudent to conduct a trial in a cohort of obese patients who receive
      posaconazole (300mg or 400mg) and define the pharmacokinetics. These will then be compared to
      the pharmacokinetics in a normal-weight group receiving 300mg posaconazole.
Obese patients with a BMI ≥ 35 kg/m2 undergoing endoscopic gastric bypass surgery will
      receive a 300 mg or 400mg dose of posaconazole. A PK curve will be determined after
      administration at t=0.45, 0.75, 1, 1.5, 2, 4, 8, 12, 24, and (if feasible) 48 hours post
      infusion. Blood samples (4 mL) on PK days will be taken to obtain at least 2.0 mL of plasma.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects.
primary purpose: Basic Science
masking: None (Open Label)
measure: Posaconazole exposure
time frame: Through study completion (usually after 24 or 48 hours)
description: The concentration-time curve of posaconazole in obese will be compared with that in non-obese subjects. Exposure is assessed by Area-Under-the-Curve from zero to 48 hours (AUC0-48h).
measure: Exposure with augemented posaconazol dose
time frame: Through study completion (usually after 24 or 48 hours)
description: The concentration-time curve of posaconazole in obese receiving 400mg will be compared with that in non-obese subjects. Exposure is assessed by Area-Under-the-Curve from zero to 48 hours (AUC0-48h).
arm group label: Obese subjects
arm group type: Experimental
description: Subjects with a BMI>35 kg/m2
arm group label: Non-obese subjects
arm group type: Active Comparator
description: Subjects with a BMI>18.5 and <25 kg/m2
intervention type: Drug
intervention name: Posaconazole Injection [Noxafil] 300mg
description: Single dose by intravenous infusion 300mg
arm group label: Non-obese subjects
arm group label: Obese subjects
intervention type: Drug
intervention name: Posaconazole Injection [Noxafil] 400mg
description: Single dose by intravenous infusion 400mg
arm group label: Obese subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Roger Brüggemann, PhD-PharmD
role: Principal Investigator
affiliation: Radboud University Medical Center
facility: 
facility: 
country: Netherlands
url: https://pubmed.ncbi.nlm.nih.gov/31971567/
description: paper
citation: Wasmann RE, Smit C, van Donselaar MH, van Dongen EPA, Wiezer RMJ, Verweij PE, Burger DM, Knibbe CAJ, Bruggemann RJM. Implications for IV posaconazole dosing in the era of obesity. J Antimicrob Chemother. 2020 Apr 1;75(4):1006-1013. doi: 10.1093/jac/dkz546.
PMID: 31971567
responsible party type: Sponsor
mesh term: Obesity, Morbid
mesh term: Posaconazole
sharing ipd: No