<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/NCT01667107</url>
  </required_header>
  <id_info>
    <org_study_id>5592-105</org_study_id>
    <secondary_id>2012-003140-68</secondary_id>
    <nct_id>NCT01667107</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic Analysis of Posaconazole in Lung Transplant Recipients (MK-5592-105)</brief_title>
  <acronym>PAPAL</acronym>
  <official_title>A Pharmacokinetic Analysis of Posaconazole in the Plasma and Alveolar Compartment of Lung Transplant Recipients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This single site study will examine plasma and alveolar compartment (AC) levels of&#xD;
      posaconazole in cystic fibrosis (CF) and non-cystic fibrosis (non-CF) lung transplant&#xD;
      recipients receiving routine post-operative anti-fungal prophylaxis. Invasive fungal&#xD;
      infection rates will be assessed following transplantation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated due to an unfavorable risk-benefit analysis&#xD;
  </why_stopped>
  <start_date type="Actual">January 23, 2013</start_date>
  <completion_date type="Actual">January 16, 2014</completion_date>
  <primary_completion_date type="Actual">January 16, 2014</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to Reach 90% of the Steady State Serum Concentration of Posaconazole</measure>
    <time_frame>Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43</time_frame>
    <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time to reach 90% of the steady state serum posaconazole concentration was to be estimated from fitting a linear model to the concentration data over time. The data did not permit estimation of the endpoint from the modeling proposed in the protocol.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum</measure>
    <time_frame>Up to Day 42</time_frame>
    <description>Concurrent BAL and serum samples for measurement of posaconazole concentration were to be collected during any clinically-indicated bronchoscopy. A participant could have more than 1 bronchoscopy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Develop Invasive Fungal Infection</measure>
    <time_frame>Up to Day 84</time_frame>
    <description>Invasive fungal infection was assessed using the Mycoses Study Group/European Organisation for Research and Treatment of Cancer (MSG/EORTC) criteria. Infections counted in the analysis were those classified as 'proven', 'probable', or 'possible' according to the criteria.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Fungal Infection</condition>
  <arm_group>
    <arm_group_label>Posaconazole - CF Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Posaconazole - Non-CF Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Posaconazole</intervention_name>
    <arm_group_label>Posaconazole - CF Participants</arm_group_label>
    <arm_group_label>Posaconazole - Non-CF Participants</arm_group_label>
    <other_name>SCH056592</other_name>
    <other_name>MK-5592</other_name>
    <other_name>Noxafil®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calogen®</intervention_name>
    <arm_group_label>Posaconazole - CF Participants</arm_group_label>
    <arm_group_label>Posaconazole - Non-CF Participants</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Scheduled to undergo lung transplantation&#xD;
&#xD;
          -  Able to take oral/nasogastric medication&#xD;
&#xD;
          -  Females of childbearing potential, males, and the sexual partners of males must use an&#xD;
             effective method of birth control during this study and for 6 weeks after completing&#xD;
             the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe liver disease&#xD;
&#xD;
          -  Current use of cytochrome P-450 (CYP)-3A4 inhibitors including terfenadine,&#xD;
             astemizole, cisapride, pimozide, halofantrine or quinidine within 7 days before&#xD;
             transplant&#xD;
&#xD;
          -  Treatment with posaconazole within 14 days before transplant&#xD;
&#xD;
          -  Breastfeeding&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>December 22, 2014</results_first_submitted>
  <results_first_submitted_qc>December 22, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 5, 2015</results_first_posted>
  <last_update_submitted>September 10, 2018</last_update_submitted>
  <last_update_submitted_qc>September 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 9, 2018</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>Mycoses</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>Yes</sharing_ipd>
    <ipd_description>https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>CSR Synopsis</doc_type>
      <doc_url>http://www.merck.com/clinical-trials/study.html?id=5592-105&amp;kw=5592-105&amp;tab=access</doc_url>
    </study_doc>
  </study_docs>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cystic Fibrosis Participants</title>
          <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
        </group>
        <group group_id="P2">
          <title>Non-Cystic Fibrosis Participants</title>
          <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Tolerability issues</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cystic Fibrosis Participants</title>
          <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
        </group>
        <group group_id="B2">
          <title>Non-Cystic Fibrosis Participants</title>
          <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.0" spread="7.82"/>
                    <measurement group_id="B2" value="52.4" spread="10.39"/>
                    <measurement group_id="B3" value="45.5" spread="14.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to Reach 90% of the Steady State Serum Concentration of Posaconazole</title>
        <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time to reach 90% of the steady state serum posaconazole concentration was to be estimated from fitting a linear model to the concentration data over time. The data did not permit estimation of the endpoint from the modeling proposed in the protocol.</description>
        <time_frame>Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43</time_frame>
        <population>The population to be analyzed included participants who complied with the protocol sufficiently to ensure that the results would exhibit the effects of treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Cystic Fibrosis Participants</title>
            <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
          <group group_id="O2">
            <title>Non-Cystic Fibrosis Participants</title>
            <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach 90% of the Steady State Serum Concentration of Posaconazole</title>
          <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time to reach 90% of the steady state serum posaconazole concentration was to be estimated from fitting a linear model to the concentration data over time. The data did not permit estimation of the endpoint from the modeling proposed in the protocol.</description>
          <population>The population to be analyzed included participants who complied with the protocol sufficiently to ensure that the results would exhibit the effects of treatment</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Time to Reach a Serum Concentration of Posaconazole of &gt;=0.5 mg/L</title>
        <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. A posaconazole concentration &gt;=0.5 mg/L is the therapeutic level, the concentration thought to lead to antifungal efficacy. The time at which the serum posaconazole concentration reached &gt;=0.5 mg/mL and remained at that level for all subsequent assessments was recorded.</description>
        <time_frame>Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43</time_frame>
        <population>The population analyzed included all enrolled participants who reached and maintained posaconazole concentration of &gt;=0.5 mg/L</population>
        <group_list>
          <group group_id="O1">
            <title>Cystic Fibrosis Participants</title>
            <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
          <group group_id="O2">
            <title>Non-Cystic Fibrosis Participants</title>
            <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach a Serum Concentration of Posaconazole of &gt;=0.5 mg/L</title>
          <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. A posaconazole concentration &gt;=0.5 mg/L is the therapeutic level, the concentration thought to lead to antifungal efficacy. The time at which the serum posaconazole concentration reached &gt;=0.5 mg/mL and remained at that level for all subsequent assessments was recorded.</description>
          <population>The population analyzed included all enrolled participants who reached and maintained posaconazole concentration of &gt;=0.5 mg/L</population>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.2" spread="8.82"/>
                    <measurement group_id="O2" value="11.9" spread="9.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Maximum Serum Concentration of Posaconazole (Cmax)</title>
        <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The maximum serum concentration of posaconazole was recorded.</description>
        <time_frame>Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43</time_frame>
        <population>The population analyzed included all enrolled participants</population>
        <group_list>
          <group group_id="O1">
            <title>Cystic Fibrosis Participants</title>
            <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
          <group group_id="O2">
            <title>Non-Cystic Fibrosis Participants</title>
            <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Serum Concentration of Posaconazole (Cmax)</title>
          <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The maximum serum concentration of posaconazole was recorded.</description>
          <population>The population analyzed included all enrolled participants</population>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.481" spread="0.6014"/>
                    <measurement group_id="O2" value="1.539" spread="0.8471"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Time to Maximum Serum Concentration of Posaconazole (Tmax)</title>
        <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time required to achieve the maximum serum concentration of posaconazole was recorded.</description>
        <time_frame>Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43</time_frame>
        <population>The population analyzed included all enrolled participants</population>
        <group_list>
          <group group_id="O1">
            <title>Cystic Fibrosis Participants</title>
            <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
          <group group_id="O2">
            <title>Non-Cystic Fibrosis Participants</title>
            <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Serum Concentration of Posaconazole (Tmax)</title>
          <description>Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time required to achieve the maximum serum concentration of posaconazole was recorded.</description>
          <population>The population analyzed included all enrolled participants</population>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.5" spread="12.39"/>
                    <measurement group_id="O2" value="23.1" spread="13.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum</title>
        <description>Concurrent BAL and serum samples for measurement of posaconazole concentration were to be collected during any clinically-indicated bronchoscopy. A participant could have more than 1 bronchoscopy.</description>
        <time_frame>Up to Day 42</time_frame>
        <population>The population analyzed included all enrolled participants who had BAL and serum samples collected at the time of bronchoscopy and analyzed for posaconazole concentration. A participant could have more than 1 pair of samples (BAL and serum) included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Cystic Fibrosis Participants</title>
            <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
          <group group_id="O2">
            <title>Non-Cystic Fibrosis Participants</title>
            <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum</title>
          <description>Concurrent BAL and serum samples for measurement of posaconazole concentration were to be collected during any clinically-indicated bronchoscopy. A participant could have more than 1 bronchoscopy.</description>
          <population>The population analyzed included all enrolled participants who had BAL and serum samples collected at the time of bronchoscopy and analyzed for posaconazole concentration. A participant could have more than 1 pair of samples (BAL and serum) included in the analysis.</population>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>paired BAL and serum samples</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>paired BAL and serum samples</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>BAL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.116" spread="1.1699"/>
                    <measurement group_id="O2" value="0.764" spread="0.800"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serum</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.829" spread="0.3742"/>
                    <measurement group_id="O2" value="0.7488" spread="0.3131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Spearman rank correlation between concurrent BAL and serum posaconazole concentrations</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.139</p_value>
            <method>Spearman rank correlation</method>
            <param_type>Spearman rank correlation coefficient</param_type>
            <param_value>0.53</param_value>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Spearman rank correlation between concurrent BAL and serum posaconazole concentrations</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.057</p_value>
            <method>Spearman rank correlation</method>
            <param_type>Spearman rank correlation coefficient</param_type>
            <param_value>0.59</param_value>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Develop Invasive Fungal Infection</title>
        <description>Invasive fungal infection was assessed using the Mycoses Study Group/European Organisation for Research and Treatment of Cancer (MSG/EORTC) criteria. Infections counted in the analysis were those classified as 'proven', 'probable', or 'possible' according to the criteria.</description>
        <time_frame>Up to Day 84</time_frame>
        <population>Participants were analyzed according to the group in which they were enrolled</population>
        <group_list>
          <group group_id="O1">
            <title>Cystic Fibrosis Participants</title>
            <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
          <group group_id="O2">
            <title>Non-Cystic Fibrosis Participants</title>
            <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Develop Invasive Fungal Infection</title>
          <description>Invasive fungal infection was assessed using the Mycoses Study Group/European Organisation for Research and Treatment of Cancer (MSG/EORTC) criteria. Infections counted in the analysis were those classified as 'proven', 'probable', or 'possible' according to the criteria.</description>
          <population>Participants were analyzed according to the group in which they were enrolled</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.5" lower_limit="2.2" upper_limit="47.1"/>
                    <measurement group_id="O2" value="16.7" lower_limit="5.8" upper_limit="39.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to Day 88</time_frame>
      <desc>All enrolled participants were assessed for adverse events. Adverse events that were serious and/or related to study drug were collected in the study. Related adverse events were those classified as possibly, probably, or certainly related to study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cystic Fibrosis Participants</title>
          <description>Cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
        </group>
        <group group_id="E2">
          <title>Non-Cystic Fibrosis Participants</title>
          <description>Non-cystic fibrosis participants received posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 15.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Systemic inflammatory response syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Transplant rejection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Immunosuppressant drug level decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 15.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Immunosuppressant drug level increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01667107
org study id: 5592-105
secondary id: 2012-003140-68
nct id: NCT01667107
lead sponsor: 
has dmc: No
This single site study will examine plasma and alveolar compartment (AC) levels of
      posaconazole in cystic fibrosis (CF) and non-cystic fibrosis (non-CF) lung transplant
      recipients receiving routine post-operative anti-fungal prophylaxis. Invasive fungal
      infection rates will be assessed following transplantation.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Time to Reach 90% of the Steady State Serum Concentration of Posaconazole
time frame: Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43
description: Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time to reach 90% of the steady state serum posaconazole concentration was to be estimated from fitting a linear model to the concentration data over time. The data did not permit estimation of the endpoint from the modeling proposed in the protocol.
measure: Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum
time frame: Up to Day 42
description: Concurrent BAL and serum samples for measurement of posaconazole concentration were to be collected during any clinically-indicated bronchoscopy. A participant could have more than 1 bronchoscopy.
measure: Percentage of Participants Who Develop Invasive Fungal Infection
time frame: Up to Day 84
description: Invasive fungal infection was assessed using the Mycoses Study Group/European Organisation for Research and Treatment of Cancer (MSG/EORTC) criteria. Infections counted in the analysis were those classified as 'proven', 'probable', or 'possible' according to the criteria.
arm group label: Posaconazole - CF Participants
arm group type: Experimental
description: Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.
arm group label: Posaconazole - Non-CF Participants
arm group type: Experimental
description: Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.
intervention type: Drug
intervention name: Posaconazole
arm group label: Posaconazole - CF Participants
arm group label: Posaconazole - Non-CF Participants
other name: SCH056592
other name: MK-5592
other name: Noxafil®
intervention type: Drug
intervention name: Calogen®
arm group label: Posaconazole - CF Participants
arm group label: Posaconazole - Non-CF Participants
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: United Kingdom
responsible party type: Sponsor
mesh term: Mycoses
mesh term: Posaconazole
sharing ipd: Yes
ipd description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
study doc: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 