<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/NCT02212587</url>
  </required_header>
  <id_info>
    <org_study_id>TIPBCC002</org_study_id>
    <secondary_id>165476</secondary_id>
    <nct_id>NCT02212587</nct_id>
  </id_info>
  <brief_title>Tobramycin Inhalation Powder (TIP) in Cystic Fibrosis Patients Infected With Burkholderia Cepacia Complex</brief_title>
  <official_title>Pilot Study of the in Vivo Efficacy of Tobramycin Inhalation Powder (TIP) in Cystic Fibrosis Patients Infected With Burkholderia Cepacia Complex</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Unity Health Toronto</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to determine if tobramycin inhalation powder (TIP) can reduce&#xD;
      the amount of Burkholderia Cepacia Complex (BCC) species - type of bacteria, in the sputum of&#xD;
      cystic fibrosis patient.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 1</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Change in Sputum Density of BCC in Colony Forming Units (CFUs)/ml From Day 0 to Day 28 of TIP Treatment.</measure>
    <time_frame>0 to 28 days</time_frame>
    <description>The change in sputum density of BCC in colony forming units (CFUs)/ml from day 0 to day 28 of TIP treatment. Sputum density was calculated by doing serial dilutions of sputum on agar plates and counting colony forming units expressed per ml.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Change in Pulmonary Function Tests, Including Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Maximal Mid-expiratory Flow Rate (FEF25-75), Measured at Day 0 and Day 28 of TIP Treatment.</measure>
    <time_frame>0 to 28 days</time_frame>
    <description>The main lung function measure was relative change in FEV1 from day 0 to Day 28 reported as %.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.</measure>
    <time_frame>0 to 28 days</time_frame>
    <description>We measured both neutrophil elastase sputum for participants.</description>
  </other_outcome>
  <other_outcome>
    <measure>Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment.</measure>
    <time_frame>Day 28</time_frame>
    <description>We did trough (0 hour) and peak (1 hour post dose) TIP sputum tobramycin concentrations and reported it for participants.</description>
  </other_outcome>
  <other_outcome>
    <measure>The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment.</measure>
    <time_frame>0 to 28 days</time_frame>
    <description>For all participants, the minimum inhibitory concentration of tobramycin for planktonic and biofilm grown BCC was measured in the lab on the isolate collected before and after TIP treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>The Number of Participants With Adverse Events Measured at Day 14 and at Day 28 of TIP Treatment.</measure>
    <time_frame>At Dat 0, Day 14, and Day 28</time_frame>
    <description>The number of participants with adverse events was reported for all participants in the trial.</description>
  </other_outcome>
  <other_outcome>
    <measure>The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.</measure>
    <time_frame>0 to 28 days</time_frame>
    <description>We measured both IL-8 sputum for participants.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Cystic Fibrosis</condition>
  <condition>Burkholderia Cepacia Infection</condition>
  <arm_group>
    <arm_group_label>TOBI Podhaler</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TOBI</intervention_name>
    <description>New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
    <arm_group_label>TOBI Podhaler</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 6 years or older&#xD;
&#xD;
          -  Diagnosis of CF based on the following: sweat chloride&gt;60 mEq/L or genotype with 2&#xD;
             identifiable mutations consistent with CF; and one or more clinical features&#xD;
             consistent with CF.&#xD;
&#xD;
          -  Chronically infected with a Burkholderia cepacia complex species (&gt;50% of respiratory&#xD;
             specimens positive in the 24 months prior to screening).&#xD;
&#xD;
          -  Able to produce sputum (expectorated or induced).&#xD;
&#xD;
          -  Able to reproducibly perform pulmonary function testing.&#xD;
&#xD;
          -  Written informed consent provided.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Post lung transplantation.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Acute exacerbation requiring IV or oral antibiotics within 14 days&#xD;
&#xD;
          -  Patients currently receiving inhaled tobramycin/TOBI&#xD;
&#xD;
          -  A septic or clinically unstable patient, as determined by the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Valerie Waters, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital of Sick Children</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Michael's Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5B 1W8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <results_reference>
    <citation>Waters V, Yau Y, Beaudoin T, Wettlaufer J, Tom SK, McDonald N, Rizvi L, Klingel M, Ratjen F, Tullis E. Pilot trial of tobramycin inhalation powder in cystic fibrosis patients with chronic Burkholderia cepacia complex infection. J Cyst Fibros. 2017 Jul;16(4):492-495. doi: 10.1016/j.jcf.2017.02.008. Epub 2017 Mar 3.</citation>
    <PMID>28262569</PMID>
  </results_reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <results_first_submitted>August 21, 2018</results_first_submitted>
  <results_first_submitted_qc>October 12, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 4, 2020</results_first_posted>
  <last_update_submitted>October 12, 2020</last_update_submitted>
  <last_update_submitted_qc>October 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>inhaled antibiotics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burkholderia Infections</mesh_term>
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TOBI Podhaler</title>
          <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TOBI Podhaler</title>
          <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Burkholderia cenocepacia IIIA, n (%)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Burkholderia cenocepacia IIIB, n (%)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Burkholderia multivorans, n (%)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sputum density log10 CFU/ml, median (range)</title>
          <units>log10 CFU/ml</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.9" lower_limit="3.1" upper_limit="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Change in Sputum Density of BCC in Colony Forming Units (CFUs)/ml From Day 0 to Day 28 of TIP Treatment.</title>
        <description>The change in sputum density of BCC in colony forming units (CFUs)/ml from day 0 to day 28 of TIP treatment. Sputum density was calculated by doing serial dilutions of sputum on agar plates and counting colony forming units expressed per ml.</description>
        <time_frame>0 to 28 days</time_frame>
        <population>sputum density measurements was calculated for all patients from Day 0 to Day 28</population>
        <group_list>
          <group group_id="O1">
            <title>TOBI Podhaler</title>
            <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in Sputum Density of BCC in Colony Forming Units (CFUs)/ml From Day 0 to Day 28 of TIP Treatment.</title>
          <description>The change in sputum density of BCC in colony forming units (CFUs)/ml from day 0 to day 28 of TIP treatment. Sputum density was calculated by doing serial dilutions of sputum on agar plates and counting colony forming units expressed per ml.</description>
          <population>sputum density measurements was calculated for all patients from Day 0 to Day 28</population>
          <units>CFU/ml log10</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" lower_limit="-3.9" upper_limit="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Change in Pulmonary Function Tests, Including Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Maximal Mid-expiratory Flow Rate (FEF25-75), Measured at Day 0 and Day 28 of TIP Treatment.</title>
        <description>The main lung function measure was relative change in FEV1 from day 0 to Day 28 reported as %.</description>
        <time_frame>0 to 28 days</time_frame>
        <population>All patients had lung function measures which were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>TOBI Podhaler</title>
            <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in Pulmonary Function Tests, Including Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Maximal Mid-expiratory Flow Rate (FEF25-75), Measured at Day 0 and Day 28 of TIP Treatment.</title>
          <description>The main lung function measure was relative change in FEV1 from day 0 to Day 28 reported as %.</description>
          <population>All patients had lung function measures which were analyzed.</population>
          <units>relative change in FEV1 expressed as %</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" lower_limit="-6.6" upper_limit="28.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.</title>
        <description>We measured both neutrophil elastase sputum for participants.</description>
        <time_frame>0 to 28 days</time_frame>
        <population>Sputum inflammatory markers were measured for 8 participants who could produce sputum.</population>
        <group_list>
          <group group_id="O1">
            <title>TOBI Podhaler</title>
            <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.</title>
          <description>We measured both neutrophil elastase sputum for participants.</description>
          <population>Sputum inflammatory markers were measured for 8 participants who could produce sputum.</population>
          <units>NE = ug/ml</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-51.9" lower_limit="-188.4" upper_limit="47.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment.</title>
        <description>We did trough (0 hour) and peak (1 hour post dose) TIP sputum tobramycin concentrations and reported it for participants.</description>
        <time_frame>Day 28</time_frame>
        <population>We did pre and post TIP sputum tobramycin concentrations in 9 participants at Day 28 since one patient stopped taking the drug.</population>
        <group_list>
          <group group_id="O1">
            <title>TOBI Podhaler</title>
            <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
          </group>
        </group_list>
        <measure>
          <title>Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment.</title>
          <description>We did trough (0 hour) and peak (1 hour post dose) TIP sputum tobramycin concentrations and reported it for participants.</description>
          <population>We did pre and post TIP sputum tobramycin concentrations in 9 participants at Day 28 since one patient stopped taking the drug.</population>
          <units>ug/ml</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Trough (0 hr)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="194" lower_limit="11" upper_limit="2100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Peak (1 hr post dose)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1025" lower_limit="306" upper_limit="4700"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment.</title>
        <description>For all participants, the minimum inhibitory concentration of tobramycin for planktonic and biofilm grown BCC was measured in the lab on the isolate collected before and after TIP treatment.</description>
        <time_frame>0 to 28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TOBI Podhaler</title>
            <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment.</title>
          <description>For all participants, the minimum inhibitory concentration of tobramycin for planktonic and biofilm grown BCC was measured in the lab on the isolate collected before and after TIP treatment.</description>
          <units>ug/ml (MIC50)</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="200" lower_limit="10" upper_limit="1600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="400" lower_limit="10" upper_limit="1600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Number of Participants With Adverse Events Measured at Day 14 and at Day 28 of TIP Treatment.</title>
        <description>The number of participants with adverse events was reported for all participants in the trial.</description>
        <time_frame>At Dat 0, Day 14, and Day 28</time_frame>
        <population>We observed for adverse events in all participants and reported on those that had an adverse event.</population>
        <group_list>
          <group group_id="O1">
            <title>TOBI Podhaler</title>
            <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Participants With Adverse Events Measured at Day 14 and at Day 28 of TIP Treatment.</title>
          <description>The number of participants with adverse events was reported for all participants in the trial.</description>
          <population>We observed for adverse events in all participants and reported on those that had an adverse event.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.</title>
        <description>We measured both IL-8 sputum for participants.</description>
        <time_frame>0 to 28 days</time_frame>
        <population>Sputum inflammatory markers were measured for 8 participants who could produce sputum.</population>
        <group_list>
          <group group_id="O1">
            <title>TOBI Podhaler</title>
            <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.</title>
          <description>We measured both IL-8 sputum for participants.</description>
          <population>Sputum inflammatory markers were measured for 8 participants who could produce sputum.</population>
          <units>IL-8 = ng/ml</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-127" lower_limit="-298.62" upper_limit="101.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 month</time_frame>
      <group_list>
        <group group_id="E1">
          <title>TOBI Podhaler</title>
          <description>TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Valerie Waters</name_or_title>
      <organization>Hospital of Sick Children</organization>
      <phone>416-813-1500</phone>
      <email>valerie.waters@sickkids.ca</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/NCT02212587
org study id: TIPBCC002
secondary id: 165476
nct id: NCT02212587
lead sponsor: 
has dmc: No
The objective of this study is to determine if tobramycin inhalation powder (TIP) can reduce
      the amount of Burkholderia Cepacia Complex (BCC) species - type of bacteria, in the sputum of
      cystic fibrosis patient.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Change in Sputum Density of BCC in Colony Forming Units (CFUs)/ml From Day 0 to Day 28 of TIP Treatment.
time frame: 0 to 28 days
description: The change in sputum density of BCC in colony forming units (CFUs)/ml from day 0 to day 28 of TIP treatment. Sputum density was calculated by doing serial dilutions of sputum on agar plates and counting colony forming units expressed per ml.
measure: The Change in Pulmonary Function Tests, Including Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Maximal Mid-expiratory Flow Rate (FEF25-75), Measured at Day 0 and Day 28 of TIP Treatment.
time frame: 0 to 28 days
description: The main lung function measure was relative change in FEV1 from day 0 to Day 28 reported as %.
measure: The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.
time frame: 0 to 28 days
description: We measured both neutrophil elastase sputum for participants.
measure: Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment.
time frame: Day 28
description: We did trough (0 hour) and peak (1 hour post dose) TIP sputum tobramycin concentrations and reported it for participants.
measure: The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment.
time frame: 0 to 28 days
description: For all participants, the minimum inhibitory concentration of tobramycin for planktonic and biofilm grown BCC was measured in the lab on the isolate collected before and after TIP treatment.
measure: The Number of Participants With Adverse Events Measured at Day 14 and at Day 28 of TIP Treatment.
time frame: At Dat 0, Day 14, and Day 28
description: The number of participants with adverse events was reported for all participants in the trial.
measure: The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.
time frame: 0 to 28 days
description: We measured both IL-8 sputum for participants.
arm group label: TOBI Podhaler
arm group type: Experimental
intervention type: Drug
intervention name: TOBI
description: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
arm group label: TOBI Podhaler
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: No
last name: Valerie Waters, MD
role: Principal Investigator
affiliation: Hospital of Sick Children
facility: 
facility: 
country: Canada
citation: Waters V, Yau Y, Beaudoin T, Wettlaufer J, Tom SK, McDonald N, Rizvi L, Klingel M, Ratjen F, Tullis E. Pilot trial of tobramycin inhalation powder in cystic fibrosis patients with chronic Burkholderia cepacia complex infection. J Cyst Fibros. 2017 Jul;16(4):492-495. doi: 10.1016/j.jcf.2017.02.008. Epub 2017 Mar 3.
PMID: 28262569
responsible party type: Sponsor
mesh term: Burkholderia Infections
mesh term: Cystic Fibrosis
mesh term: Fibrosis
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 