<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/NCT01684436</url>
  </required_header>
  <id_info>
    <org_study_id>APMA-DE-0812</org_study_id>
    <nct_id>NCT01684436</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Punctal Plug Insertion in Patients With Dry Eye</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Allergan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will access changes in tear protein levels and symptoms of dry eye following&#xD;
      insertion of a punctal plug.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2012</start_date>
  <completion_date type="Actual">July 31, 2013</completion_date>
  <primary_completion_date type="Actual">July 31, 2013</primary_completion_date>
  <phase>Phase 4</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>Concentration of Tear Cytokine Levels Before Punctal Plug Insertion in the Study Eye</measure>
    <time_frame>Week 0 (Baseline)</time_frame>
    <description>A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentration of Tear Cytokine Levels Following Punctal Plug Insertion in the Study Eye</measure>
    <time_frame>Week 3</time_frame>
    <description>A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Corneal Fluorescein Staining Score in the Study Eye</measure>
    <time_frame>Week 0 (Baseline), Week 3</time_frame>
    <description>The cornea is evaluated following ocular administration of fluorescein stain in the study eye. The cornea is the transparent front part of the eye which covers the iris and pupil. The cornea is divided into 5 regions. Each region is scored according to the extent of staining, with scores ranging from 0 to 4 points: 0=non-staining to 4=regional whole staining of the cornea with 0.5 unit intervals. The higher the staining score, the worse the dry eye condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tear Film Break-up Time (TBUT)</measure>
    <time_frame>Week 0 (Baseline), Week 3</time_frame>
    <description>TBUT is defined as the time to initial breakup of the tear film following a blink. The longer it takes, the more stable the tear film.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Schirmer's Test Score</measure>
    <time_frame>Week 0 (Baseline), Week 3</time_frame>
    <description>The Schirmer's Test measures the rate of tear secretion by the eye over 5 minutes (min). The results indicate the presence of dry eye (Normal = greater than or equal to 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dry Eye Questionnaire Irritation Score</measure>
    <time_frame>Week 0 (Baseline), Week 3</time_frame>
    <description>Severity of dry eye irritation is rated by the patient using a visual analogue scale (VAS). Patients put a mark on a 100 millimeter line where 0 (far left on the line)=no symptoms to 100 (far right on the line)=most severe symptoms. The higher the score, the more severe the symptoms.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Dry Eye</condition>
  <arm_group>
    <arm_group_label>Punctal plug</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Punctal plugs inserted into the study eye on Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Punctal Plug</intervention_name>
    <description>Punctal plugs inserted into the study eye on Day 1.</description>
    <arm_group_label>Punctal plug</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with moderate to severe dry eye&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous punctal plug insertion in the last 3 months or presence of plugs at the time&#xD;
             of study&#xD;
&#xD;
          -  Contact lens wear in the 7 days prior to study start or during the study&#xD;
&#xD;
          -  LASIK procedure in the last year&#xD;
&#xD;
          -  Cataract or other eye surgery in the last 3 months&#xD;
&#xD;
          -  Corneal grafts&#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>Allergan</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Tong L, Beuerman R, Simonyi S, Hollander DA, Stern ME. Effects of Punctal Occlusion on Clinical Signs and Symptoms and on Tear Cytokine Levels in Patients with Dry Eye. Ocul Surf. 2016 Apr;14(2):233-41. doi: 10.1016/j.jtos.2015.12.004. Epub 2016 Jan 13.</citation>
    <PMID>26774908</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <results_first_submitted>July 10, 2014</results_first_submitted>
  <results_first_submitted_qc>August 14, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 15, 2014</results_first_posted>
  <last_update_submitted>April 9, 2019</last_update_submitted>
  <last_update_submitted_qc>April 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 17, 2019</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>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Punctal Plug</title>
          <description>Punctal plugs inserted into the study eye on Day 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </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>
      <population>The number of participants for analysis includes all patients who completed the study</population>
      <group_list>
        <group group_id="B1">
          <title>Punctal Plug</title>
          <description>Punctal plugs inserted into the study eye on Day 1.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
          </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="49.8" spread="14.1"/>
                  </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="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Concentration of Tear Cytokine Levels Before Punctal Plug Insertion in the Study Eye</title>
        <description>A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.</description>
        <time_frame>Week 0 (Baseline)</time_frame>
        <population>All patients who completed the study</population>
        <group_list>
          <group group_id="O1">
            <title>Punctal Plug</title>
            <description>Punctal plugs inserted into the study eye on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Tear Cytokine Levels Before Punctal Plug Insertion in the Study Eye</title>
          <description>A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.</description>
          <population>All patients who completed the study</population>
          <units>picogram/milliliter/millimeter(pg/ml/mm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Interferon (IFN)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.24" spread="2.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-10 (IL10)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.69" spread="3.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-12 (IL12)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.08" spread="9.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-13 (IL13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.81" spread="26.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-17A (IL17A)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.57" spread="0.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-1B (IL1B)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.63" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Matrix metallopeptidase 9 (MMP9)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1519.82" spread="1516.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-2 (IL2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.88" spread="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-4 (IL4)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.66" spread="21.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-6 (IL6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.11" spread="6.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-8 (IL8)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.00" spread="55.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interferon γ-Induced Protein-10 (IP10)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2384.86" spread="1198.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocyte Chemotactic Protein 1 (MCP1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.08" spread="46.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Macrophage Inflammatory Protein 1 Alpha (MIP1A)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.59" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Regulate Activation Normal T-Cell Express (RANTE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.20" spread="15.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tumor Necrosis Factor Alpha (TNFA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.54" spread="1.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Corneal Fluorescein Staining Score in the Study Eye</title>
        <description>The cornea is evaluated following ocular administration of fluorescein stain in the study eye. The cornea is the transparent front part of the eye which covers the iris and pupil. The cornea is divided into 5 regions. Each region is scored according to the extent of staining, with scores ranging from 0 to 4 points: 0=non-staining to 4=regional whole staining of the cornea with 0.5 unit intervals. The higher the staining score, the worse the dry eye condition.</description>
        <time_frame>Week 0 (Baseline), Week 3</time_frame>
        <population>All patients who completed the study</population>
        <group_list>
          <group group_id="O1">
            <title>Punctal Plug</title>
            <description>Punctal plugs inserted into the study eye on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Corneal Fluorescein Staining Score in the Study Eye</title>
          <description>The cornea is evaluated following ocular administration of fluorescein stain in the study eye. The cornea is the transparent front part of the eye which covers the iris and pupil. The cornea is divided into 5 regions. Each region is scored according to the extent of staining, with scores ranging from 0 to 4 points: 0=non-staining to 4=regional whole staining of the cornea with 0.5 unit intervals. The higher the staining score, the worse the dry eye condition.</description>
          <population>All patients who completed the study</population>
          <units>Scores on a Scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0 (Baseline): Superior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.57" spread="0.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 0 (Baseline): Inferior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.33" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 0 (Baseline): Nasal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.67" spread="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 0 (Baseline): Temporal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.72" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 0 (Baseline): Central</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.91" spread="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3: Superior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.48" spread="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3: Inferior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.22" spread="0.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3: Nasal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3: Temporal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.36" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3: Central</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.57" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tear Film Break-up Time (TBUT)</title>
        <description>TBUT is defined as the time to initial breakup of the tear film following a blink. The longer it takes, the more stable the tear film.</description>
        <time_frame>Week 0 (Baseline), Week 3</time_frame>
        <population>All patients who completed the study</population>
        <group_list>
          <group group_id="O1">
            <title>Punctal Plug</title>
            <description>Punctal plugs inserted into the study eye on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Tear Film Break-up Time (TBUT)</title>
          <description>TBUT is defined as the time to initial breakup of the tear film following a blink. The longer it takes, the more stable the tear film.</description>
          <population>All patients who completed the study</population>
          <units>Seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0 (Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.21" spread="0.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.42" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Schirmer's Test Score</title>
        <description>The Schirmer's Test measures the rate of tear secretion by the eye over 5 minutes (min). The results indicate the presence of dry eye (Normal = greater than or equal to 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye.</description>
        <time_frame>Week 0 (Baseline), Week 3</time_frame>
        <population>All patients who completed the study</population>
        <group_list>
          <group group_id="O1">
            <title>Punctal Plug</title>
            <description>Punctal plugs inserted into the study eye on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Schirmer's Test Score</title>
          <description>The Schirmer's Test measures the rate of tear secretion by the eye over 5 minutes (min). The results indicate the presence of dry eye (Normal = greater than or equal to 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye.</description>
          <population>All patients who completed the study</population>
          <units>Millimeters (mm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0 (Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.07" spread="2.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.28" spread="5.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Dry Eye Questionnaire Irritation Score</title>
        <description>Severity of dry eye irritation is rated by the patient using a visual analogue scale (VAS). Patients put a mark on a 100 millimeter line where 0 (far left on the line)=no symptoms to 100 (far right on the line)=most severe symptoms. The higher the score, the more severe the symptoms.</description>
        <time_frame>Week 0 (Baseline), Week 3</time_frame>
        <population>All patients who completed the study</population>
        <group_list>
          <group group_id="O1">
            <title>Punctal Plug</title>
            <description>Punctal plugs inserted into the study eye on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Dry Eye Questionnaire Irritation Score</title>
          <description>Severity of dry eye irritation is rated by the patient using a visual analogue scale (VAS). Patients put a mark on a 100 millimeter line where 0 (far left on the line)=no symptoms to 100 (far right on the line)=most severe symptoms. The higher the score, the more severe the symptoms.</description>
          <population>All patients who completed the study</population>
          <units>Millimeters (mm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 0 (Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.81" spread="26.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.22" spread="24.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Concentration of Tear Cytokine Levels Following Punctal Plug Insertion in the Study Eye</title>
        <description>A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.</description>
        <time_frame>Week 3</time_frame>
        <population>All patients who completed the study</population>
        <group_list>
          <group group_id="O1">
            <title>Punctal Plug</title>
            <description>Punctal plugs inserted into the study eye on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Tear Cytokine Levels Following Punctal Plug Insertion in the Study Eye</title>
          <description>A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.</description>
          <population>All patients who completed the study</population>
          <units>picogram/milliliter/millimeter(pg/ml/mm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IFN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.12" spread="2.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.97" spread="3.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.34" spread="6.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL13</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.14" spread="23.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL17A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.55" spread="0.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL1B</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.10" spread="1.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MMP9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1445.53" spread="1415.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.05" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.75" spread="8.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.31" spread="3.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.07" spread="57.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IP10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2769.17" spread="1479.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MCP1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.08" spread="62.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MIP1A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.61" spread="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RANTE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.55" spread="26.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNFA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.37" spread="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events (AEs) and serious adverse events (SAEs) were collected over the 3 week study period.</time_frame>
      <desc>All patients enrolled in the study were used for the analysis of adverse events (AEs) and serious adverse events (SAEs).</desc>
      <group_list>
        <group group_id="E1">
          <title>Punctal Plug</title>
          <description>Punctal plugs inserted into the study eye on Day 1.</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="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="30"/>
              </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>A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is at least 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Vice President Medical Affairs,</name_or_title>
      <organization>Allergan, Inc</organization>
      <phone>714-246-4500</phone>
      <email>clinicaltrials@allergan.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/NCT01684436
org study id: APMA-DE-0812
nct id: NCT01684436
lead sponsor: 
has dmc: No
This study will access changes in tear protein levels and symptoms of dry eye following
      insertion of a punctal plug.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Concentration of Tear Cytokine Levels Before Punctal Plug Insertion in the Study Eye
time frame: Week 0 (Baseline)
description: A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.
measure: Concentration of Tear Cytokine Levels Following Punctal Plug Insertion in the Study Eye
time frame: Week 3
description: A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.
measure: Corneal Fluorescein Staining Score in the Study Eye
time frame: Week 0 (Baseline), Week 3
description: The cornea is evaluated following ocular administration of fluorescein stain in the study eye. The cornea is the transparent front part of the eye which covers the iris and pupil. The cornea is divided into 5 regions. Each region is scored according to the extent of staining, with scores ranging from 0 to 4 points: 0=non-staining to 4=regional whole staining of the cornea with 0.5 unit intervals. The higher the staining score, the worse the dry eye condition.
measure: Tear Film Break-up Time (TBUT)
time frame: Week 0 (Baseline), Week 3
description: TBUT is defined as the time to initial breakup of the tear film following a blink. The longer it takes, the more stable the tear film.
measure: Schirmer's Test Score
time frame: Week 0 (Baseline), Week 3
description: The Schirmer's Test measures the rate of tear secretion by the eye over 5 minutes (min). The results indicate the presence of dry eye (Normal = greater than or equal to 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye.
measure: Dry Eye Questionnaire Irritation Score
time frame: Week 0 (Baseline), Week 3
description: Severity of dry eye irritation is rated by the patient using a visual analogue scale (VAS). Patients put a mark on a 100 millimeter line where 0 (far left on the line)=no symptoms to 100 (far right on the line)=most severe symptoms. The higher the score, the more severe the symptoms.
arm group label: Punctal plug
arm group type: Experimental
description: Punctal plugs inserted into the study eye on Day 1.
intervention type: Device
intervention name: Punctal Plug
description: Punctal plugs inserted into the study eye on Day 1.
arm group label: Punctal plug
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Allergan
facility: 
country: Singapore
citation: Tong L, Beuerman R, Simonyi S, Hollander DA, Stern ME. Effects of Punctal Occlusion on Clinical Signs and Symptoms and on Tear Cytokine Levels in Patients with Dry Eye. Ocul Surf. 2016 Apr;14(2):233-41. doi: 10.1016/j.jtos.2015.12.004. Epub 2016 Jan 13.
PMID: 26774908
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 