<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/NCT02193490</url>
  </required_header>
  <id_info>
    <org_study_id>2012-1106</org_study_id>
    <nct_id>NCT02193490</nct_id>
  </id_info>
  <brief_title>DNase Treatment for Dry Eyes</brief_title>
  <official_title>Safety and Efficacy Of Recombinant Human Deoxyribonuclease Eye Drops In Patients With Sjogren's and Non-Sjogren Dry Eye Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Illinois at Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Research to Prevent Blindness</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Illinois at Chicago</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the tolerability and preliminary efficacy of DNase&#xD;
      eye drops in patients with Sjogren's and Non-Sjogren Dry Eye Disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor ceased sponsorship and terminated the research citing slow accrual of subjects in this&#xD;
    clinical trial.&#xD;
  </why_stopped>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">October 11, 2017</completion_date>
  <primary_completion_date type="Actual">October 11, 2017</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining</measure>
    <time_frame>Between baseline and at 8 weeks of treatment</time_frame>
    <description>Corneal staining score as measured by Rose Bengal (RB) dye staining using National Eye Institute (NEI) 1995 workshop grading scale. The dye was applied to each eye and a slit lamp was used to observe corneal staining. The NEI scale relies on a chart that divides the cornea into 5 sections and assigns a value from 0 (absent) to 3 (severe) to each section, based on the density of punctate staining, final staining score being the sum of individual section scores, for a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with RB dye defined as a score of 0 indicating the best outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Change in the Ocular Surface Disease Index Score</measure>
    <time_frame>Between baseline and at 8 weeks of treatment</time_frame>
    <description>Ocular Surface Disease Index (OSDI), a 12-item questionnaire, assesses symptom of ocular irritation in dry eye disease (DED) and how it affects functioning related to vision in the past week. It has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on 0 to 4 scale with 0 being &quot;none of the time&quot; and 4 being &quot;all of the time.&quot; OSDI score range from 0-100 with score 0-12 being normal, 13-22 being mild DED, 23-32 being moderate DED, and &gt;33 being severe DED. OSDI=[(sum of scores for questions answered)×100]/[(total questions answered)×4]</description>
  </primary_outcome>
  <other_outcome>
    <measure>The Change in Mucoid Debris Strands Between Baseline and 8-weeks</measure>
    <time_frame>Between baseline and 8-weeks of treatment</time_frame>
    <description>The presence of mucoid debris/strands over the ocular surface was assessed and the amount graded as the absence of mucoid debris (0) or presence of mucoid debris (1+, 2+ or 3+) with a bigger number indicating greater presence of mucoid debris with &quot;3+&quot; implying presence of the highest amount of mucoid debris and indicating the worst outcome.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Dry Eye</condition>
  <arm_group>
    <arm_group_label>DNase</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>DNase 0.1% eye drops four times a day for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vehicle</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drug vehicle eye drops four times a day for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DNase</intervention_name>
    <description>DNase 0.1% eye drops four times a day for 8 weeks</description>
    <arm_group_label>DNase</arm_group_label>
    <other_name>Pulmozyme</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vehicle</intervention_name>
    <description>Drug vehicle eye drops four times a day for 8 weeks</description>
    <arm_group_label>Vehicle</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18 years or older.&#xD;
&#xD;
          -  Capable of giving informed consent and does provide informed consent.&#xD;
&#xD;
          -  Documented Dry Eye Disease for at least 6 months.&#xD;
&#xD;
          -  Schirmer I &lt;10&#xD;
&#xD;
          -  Corneal/ conjunctival (Rose Bengal) staining ≥1&#xD;
&#xD;
          -  Ocular symptoms must be considered as annoying or activity limiting (OSDI ≥13; mild).&#xD;
&#xD;
          -  Women must be post-menopausal ≥ 1 year, or surgically sterilized. If not, a negative&#xD;
             urine pregnancy test is required within 14 days of receiving her first dose of test&#xD;
             medication (placebo/ study drug) along with definite evidence of contraceptive use&#xD;
             during the duration of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergic to Deoxyribonuclease eye drops or any similar products, or excipients of&#xD;
             Deoxyribonuclease eye drops 0.1%.&#xD;
&#xD;
          -  Receiving or have received within 30 days any experimental systemic medication.&#xD;
&#xD;
          -  Active ocular infection or ocular allergies.&#xD;
&#xD;
          -  Any history of eyelid surgery or ocular surgery within the past 3 months.&#xD;
&#xD;
          -  Corneal epithelial defect larger than 1 mm2 in either eye.&#xD;
&#xD;
          -  The use of topical cyclosporine or corticosteroids within 2 weeks of enrollment&#xD;
&#xD;
          -  Have active drug/alcohol dependence or abuse history&#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>Sandeep Jain, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Illinois at Chicago</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Translational Clinic of Corneal Neurobiology laboratory, Illinois Eye and Ear Infirmary, University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://chicago.medicine.uic.edu/directory/name/sandeep-jain-md-jain/</url>
    <description>Principal Investigator description</description>
  </link>
  <reference>
    <citation>Tibrewal S, Sarkar J, Jassim SH, Gandhi S, Sonawane S, Chaudhary S, Byun YS, Ivanir Y, Hallak J, Horner JH, Newcomb M, Jain S. Tear fluid extracellular DNA: diagnostic and therapeutic implications in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Dec 11;54(13):8051-61. doi: 10.1167/iovs.13-12844.</citation>
    <PMID>24255046</PMID>
  </reference>
  <reference>
    <citation>Sonawane S, Khanolkar V, Namavari A, Chaudhary S, Gandhi S, Tibrewal S, Jassim SH, Shaheen B, Hallak J, Horner JH, Newcomb M, Sarkar J, Jain S. Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm for inflammation in dry eye disease. Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8253-63. doi: 10.1167/iovs.12-10430.</citation>
    <PMID>23169882</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <results_first_submitted>July 23, 2019</results_first_submitted>
  <results_first_submitted_qc>October 16, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 5, 2019</results_first_posted>
  <last_update_submitted>January 15, 2020</last_update_submitted>
  <last_update_submitted_qc>January 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Illinois at Chicago</investigator_affiliation>
    <investigator_full_name>Sandeep Jain, MD</investigator_full_name>
    <investigator_title>Associate Professor of Ophthalmology</investigator_title>
  </responsible_party>
  <keyword>DNase, Pulmozyme, dry eye disease, treatment</keyword>
  <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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 6, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT02193490/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This single-center study was conducted at the Department of Ophthalmology Clinical Trials and Translational Center, the University of Illinois at Chicago (UIC).</recruitment_details>
      <pre_assignment_details>A 2-week washout period was required if topical corticosteroids or topical cyclosporine were discontinued before enrollment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>DNase</title>
          <description>DNase 0.1% eye drops four times a day for 8 weeks&#xD;
DNase: DNase 0.1% eye drops four times a day for 8 weeks</description>
        </group>
        <group group_id="P2">
          <title>Vehicle</title>
          <description>Drug vehicle eye drops four times a day for 8 weeks&#xD;
Vehicle: Drug vehicle eye drops four times a day for 8 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>DNase</title>
          <description>DNase 0.1% eye drops four times a day for 8 weeks&#xD;
DNase: DNase 0.1% eye drops four times a day for 8 weeks</description>
        </group>
        <group group_id="B2">
          <title>Vehicle</title>
          <description>Drug vehicle eye drops four times a day for 8 weeks&#xD;
Vehicle: Drug vehicle eye drops four times a day for 8 weeks</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="25"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="47"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57" lower_limit="44" upper_limit="64"/>
                    <measurement group_id="B2" value="55.5" lower_limit="50.2" upper_limit="60.8"/>
                    <measurement group_id="B3" value="56" lower_limit="47" upper_limit="62.5"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diagnosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Sjogren's Syndrome</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-Sjogren's DED</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ocular GVHD</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>OSDI</title>
          <description>Ocular Surface Disease Index (OSDI), 12-item questionnaire, assesses symptom of ocular irritation in dry eye disease (DED) and how it affects functioning related to vision in past week. It has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on 0 to 4 scale with 0 being &quot;none of the time&quot; and 4 being &quot;all of the time.&quot; OSDI score range from 0-100 with score 0-12 being normal, 13-22 being mild DED, 23-32 being moderate DED, and &gt;33 being severe DED. OSDI=[(sum of scores for questions answered)×100]/[(total questions answered)×4]</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50" lower_limit="32.5" upper_limit="62.5"/>
                    <measurement group_id="B2" value="49" lower_limit="36.6" upper_limit="72.9"/>
                    <measurement group_id="B3" value="50" lower_limit="33.65" upper_limit="71.335"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Corneal Staining</title>
          <description>Corneal staining score as measured by Rose Bengal (RB) dye staining using National Eye Institute (NEI) grading scale. The dye was applied to each eye and a slit lamp was used to observe corneal staining. The NEI scale relies on a chart that divides the cornea into 5 sections and assigns a value from 0 (absent) to 3 (severe) to each section, based on the density of punctate staining, final staining score being the sum of individual section scores with a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with RB dye defined as a score of 0 indicating the best outcome.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <title>Oculus Dexter (OD)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5" lower_limit="3" upper_limit="7"/>
                    <measurement group_id="B2" value="5" lower_limit="4" upper_limit="8"/>
                    <measurement group_id="B3" value="5" lower_limit="3" upper_limit="6.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Oculus Sinister (OS)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5" lower_limit="3" upper_limit="6"/>
                    <measurement group_id="B2" value="5" lower_limit="4" upper_limit="8"/>
                    <measurement group_id="B3" value="5" lower_limit="4" upper_limit="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mucoid Debris Strands</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>OD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Schirmer I</title>
          <description>The Schirmer's I tests consists of a thin strip of filter paper placed in lower conjunctival fornix (between the lower eyelid and ocular surface) for 5 minutes. The length of wetting of the strip is used as a measure of tear production by the eye. A normal level of production is considered to be over 10 millimeters (mm) of tears on the paper. Anything under 10 mm is considered to be an abnormally low level of tear production. A measurement of less than 5 mm is considered severe dry eye.</description>
          <units>mm</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <title>OD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2" lower_limit="0" upper_limit="4"/>
                    <measurement group_id="B2" value="0.75" lower_limit="0" upper_limit="1"/>
                    <measurement group_id="B3" value="1" lower_limit="0" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2" lower_limit="0" upper_limit="5"/>
                    <measurement group_id="B2" value="0.25" lower_limit="0" upper_limit="1.75"/>
                    <measurement group_id="B3" value="1" lower_limit="0" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Conjunctival Staining</title>
          <description>Conjunctival staining score as measured by Rose Bengal (RB) dye staining using National Eye Institute (NEI) grading scale. The dye was applied to each eye and a slit lamp was used to observe conjunctival staining. The NEI scale relies on a chart that divides the conjunctiva into 2 sections and assigns a value from 0 (absent) to 3 (severe) to each section, based on the density of punctate staining, final staining score being the sum of individual section scores, for a range of 0-6 points. Complete conjunctival staining clearance with RB dye defined as a score of 0 indicating the best outcome.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <title>OD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.00" lower_limit="2" upper_limit="4"/>
                    <measurement group_id="B2" value="4.00" lower_limit="3" upper_limit="6"/>
                    <measurement group_id="B3" value="4" lower_limit="2" upper_limit="4.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.00" lower_limit="2" upper_limit="4"/>
                    <measurement group_id="B2" value="4.00" lower_limit="2" upper_limit="5"/>
                    <measurement group_id="B3" value="4" lower_limit="2" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Conjunctival Injection</title>
          <description>Ocular surface redness (nasal or temporal) will be assessed using the Validated Bulbar Redness grading scale (VBR). VBR consists of 10 images illustrating different degrees of ocular surface redness (OR), ranging from normal to severe, and each image is assigned a value in an order of ascending severity (10-100). Subjects were examined by a slit-lamp and the bulbar conjunctival injection of the subject's eye (nasal and temporal) will be compared to the reference images and graded accordingly.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <title>Temporal OD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40" lower_limit="30" upper_limit="60"/>
                    <measurement group_id="B2" value="45" lower_limit="40" upper_limit="60"/>
                    <measurement group_id="B3" value="40" lower_limit="40" upper_limit="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temporal OS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40" lower_limit="40" upper_limit="60"/>
                    <measurement group_id="B2" value="45" lower_limit="40" upper_limit="60"/>
                    <measurement group_id="B3" value="40" lower_limit="40" upper_limit="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal OD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40" lower_limit="30" upper_limit="50"/>
                    <measurement group_id="B2" value="40" lower_limit="40" upper_limit="57.5"/>
                    <measurement group_id="B3" value="40" lower_limit="35" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal OS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40" lower_limit="30" upper_limit="50"/>
                    <measurement group_id="B2" value="45" lower_limit="40" upper_limit="60"/>
                    <measurement group_id="B3" value="40" lower_limit="30" upper_limit="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Corneal Filaments</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>OD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tolerability [Oculus Uterque (OU)]</title>
          <description>To see how subjects react to the study medication, their first dose was given by the investigator at baseline visit in the clinic itself. Afterward, subjects were asked to rate tolerability of the drug on the Visual Analogue Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end. The VAS ratings were completed after the administration of the test medication. Subjects placed a single slash mark across the horizontal line between the end labeled &quot;completely intolerable&quot; (0 mm) and &quot;easily tolerable&quot; (100mm).</description>
          <population>Missing data for one patient.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Tolerability (90)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="21"/>
                    <count group_id="B3" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tolerability (100)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="21"/>
                    <count group_id="B3" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Intraocular Pressure (IOP)</title>
          <units>mmHg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <title>OD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.5" lower_limit="15" upper_limit="20"/>
                    <measurement group_id="B2" value="18" lower_limit="16" upper_limit="20"/>
                    <measurement group_id="B3" value="18" lower_limit="15.625" upper_limit="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OS</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="22"/>
                    <count group_id="B3" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18.5" lower_limit="16" upper_limit="22"/>
                    <measurement group_id="B2" value="18" lower_limit="15.5" upper_limit="20"/>
                    <measurement group_id="B3" value="18" lower_limit="16" upper_limit="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining</title>
        <description>Corneal staining score as measured by Rose Bengal (RB) dye staining using National Eye Institute (NEI) 1995 workshop grading scale. The dye was applied to each eye and a slit lamp was used to observe corneal staining. The NEI scale relies on a chart that divides the cornea into 5 sections and assigns a value from 0 (absent) to 3 (severe) to each section, based on the density of punctate staining, final staining score being the sum of individual section scores, for a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with RB dye defined as a score of 0 indicating the best outcome.</description>
        <time_frame>Between baseline and at 8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>DNase</title>
            <description>DNase 0.1% eye drops four times a day for 8 weeks&#xD;
DNase: DNase 0.1% eye drops four times a day for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>Drug vehicle eye drops four times a day for 8 weeks&#xD;
Vehicle: Drug vehicle eye drops four times a day for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining</title>
          <description>Corneal staining score as measured by Rose Bengal (RB) dye staining using National Eye Institute (NEI) 1995 workshop grading scale. The dye was applied to each eye and a slit lamp was used to observe corneal staining. The NEI scale relies on a chart that divides the cornea into 5 sections and assigns a value from 0 (absent) to 3 (severe) to each section, based on the density of punctate staining, final staining score being the sum of individual section scores, for a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with RB dye defined as a score of 0 indicating the best outcome.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>OD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.00" lower_limit="-3.00" upper_limit="-1.00"/>
                    <measurement group_id="O2" value="0.00" lower_limit="-0.25" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.00" lower_limit="-3.00" upper_limit="-1.00"/>
                    <measurement group_id="O2" value="0.00" lower_limit="0.00" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Change in the Ocular Surface Disease Index Score</title>
        <description>Ocular Surface Disease Index (OSDI), a 12-item questionnaire, assesses symptom of ocular irritation in dry eye disease (DED) and how it affects functioning related to vision in the past week. It has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on 0 to 4 scale with 0 being &quot;none of the time&quot; and 4 being &quot;all of the time.&quot; OSDI score range from 0-100 with score 0-12 being normal, 13-22 being mild DED, 23-32 being moderate DED, and &gt;33 being severe DED. OSDI=[(sum of scores for questions answered)×100]/[(total questions answered)×4]</description>
        <time_frame>Between baseline and at 8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>DNase</title>
            <description>DNase 0.1% eye drops four times a day for 8 weeks&#xD;
DNase: DNase 0.1% eye drops four times a day for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>Drug vehicle eye drops four times a day for 8 weeks&#xD;
Vehicle: Drug vehicle eye drops four times a day for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in the Ocular Surface Disease Index Score</title>
          <description>Ocular Surface Disease Index (OSDI), a 12-item questionnaire, assesses symptom of ocular irritation in dry eye disease (DED) and how it affects functioning related to vision in the past week. It has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on 0 to 4 scale with 0 being &quot;none of the time&quot; and 4 being &quot;all of the time.&quot; OSDI score range from 0-100 with score 0-12 being normal, 13-22 being mild DED, 23-32 being moderate DED, and &gt;33 being severe DED. OSDI=[(sum of scores for questions answered)×100]/[(total questions answered)×4]</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>OD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.75" lower_limit="-37" upper_limit="-11.80"/>
                    <measurement group_id="O2" value="-8.43" lower_limit="-25" upper_limit="-0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.75" lower_limit="-37" upper_limit="-11.80"/>
                    <measurement group_id="O2" value="-8.43" lower_limit="-25" upper_limit="-0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.078</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Change in Mucoid Debris Strands Between Baseline and 8-weeks</title>
        <description>The presence of mucoid debris/strands over the ocular surface was assessed and the amount graded as the absence of mucoid debris (0) or presence of mucoid debris (1+, 2+ or 3+) with a bigger number indicating greater presence of mucoid debris with &quot;3+&quot; implying presence of the highest amount of mucoid debris and indicating the worst outcome.</description>
        <time_frame>Between baseline and 8-weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>DNase</title>
            <description>DNase 0.1% eye drops four times a day for 8 weeks&#xD;
DNase: DNase 0.1% eye drops four times a day for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>Drug vehicle eye drops four times a day for 8 weeks&#xD;
Vehicle: Drug vehicle eye drops four times a day for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in Mucoid Debris Strands Between Baseline and 8-weeks</title>
          <description>The presence of mucoid debris/strands over the ocular surface was assessed and the amount graded as the absence of mucoid debris (0) or presence of mucoid debris (1+, 2+ or 3+) with a bigger number indicating greater presence of mucoid debris with &quot;3+&quot; implying presence of the highest amount of mucoid debris and indicating the worst outcome.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>OD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.00" lower_limit="-2.00" upper_limit="0.00"/>
                    <measurement group_id="O2" value="0.00" lower_limit="0.00" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="-1.00" upper_limit="0.00"/>
                    <measurement group_id="O2" value="0.00" lower_limit="0.00" upper_limit="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Between baseline and 8-weeks of treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>DNase</title>
          <description>DNase 0.1% eye drops four times a day for 8 weeks&#xD;
DNase: DNase 0.1% eye drops four times a day for 8 weeks</description>
        </group>
        <group group_id="E2">
          <title>Vehicle</title>
          <description>Drug vehicle eye drops four times a day for 8 weeks&#xD;
Vehicle: Drug vehicle eye drops four times a day for 8 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>4</frequency_threshold>
        <default_assessment>Non-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="9" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Grittines</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Burning</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Light Sensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Itching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <limitations_and_caveats>Outcomes of this clinical trial shouldn't be over-interpreted for benefit. Accurate assessment of therapeutic implications of DNase eye drops will only be possible after adequately powered definitive pivotal trials. Small sample size is a limitation.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Sandeep Jain</name_or_title>
      <organization>University of Illinois Chicago</organization>
      <phone>312-996-4476</phone>
      <email>jains@uic.edu</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/NCT02193490
org study id: 2012-1106
nct id: NCT02193490
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate the tolerability and preliminary efficacy of DNase
      eye drops in patients with Sjogren's and Non-Sjogren Dry Eye Disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The Change in Corneal Surface Staining as Measured by Rose Bengal Dye Staining
time frame: Between baseline and at 8 weeks of treatment
description: Corneal staining score as measured by Rose Bengal (RB) dye staining using National Eye Institute (NEI) 1995 workshop grading scale. The dye was applied to each eye and a slit lamp was used to observe corneal staining. The NEI scale relies on a chart that divides the cornea into 5 sections and assigns a value from 0 (absent) to 3 (severe) to each section, based on the density of punctate staining, final staining score being the sum of individual section scores, for a range of 0 (minimum) -15 (maximum) points. Complete corneal staining clearance with RB dye defined as a score of 0 indicating the best outcome.
measure: The Change in the Ocular Surface Disease Index Score
time frame: Between baseline and at 8 weeks of treatment
description: Ocular Surface Disease Index (OSDI), a 12-item questionnaire, assesses symptom of ocular irritation in dry eye disease (DED) and how it affects functioning related to vision in the past week. It has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on 0 to 4 scale with 0 being "none of the time" and 4 being "all of the time." OSDI score range from 0-100 with score 0-12 being normal, 13-22 being mild DED, 23-32 being moderate DED, and >33 being severe DED. OSDI=[(sum of scores for questions answered)×100]/[(total questions answered)×4]
measure: The Change in Mucoid Debris Strands Between Baseline and 8-weeks
time frame: Between baseline and 8-weeks of treatment
description: The presence of mucoid debris/strands over the ocular surface was assessed and the amount graded as the absence of mucoid debris (0) or presence of mucoid debris (1+, 2+ or 3+) with a bigger number indicating greater presence of mucoid debris with "3+" implying presence of the highest amount of mucoid debris and indicating the worst outcome.
arm group label: DNase
arm group type: Active Comparator
description: DNase 0.1% eye drops four times a day for 8 weeks
arm group label: Vehicle
arm group type: Placebo Comparator
description: Drug vehicle eye drops four times a day for 8 weeks
intervention type: Drug
intervention name: DNase
description: DNase 0.1% eye drops four times a day for 8 weeks
arm group label: DNase
other name: Pulmozyme
intervention type: Drug
intervention name: Vehicle
description: Drug vehicle eye drops four times a day for 8 weeks
arm group label: Vehicle
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sandeep Jain, MD
role: Principal Investigator
affiliation: University of Illinois at Chicago
facility: 
country: United States
url: https://chicago.medicine.uic.edu/directory/name/sandeep-jain-md-jain/
description: Principal Investigator description
citation: Tibrewal S, Sarkar J, Jassim SH, Gandhi S, Sonawane S, Chaudhary S, Byun YS, Ivanir Y, Hallak J, Horner JH, Newcomb M, Jain S. Tear fluid extracellular DNA: diagnostic and therapeutic implications in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Dec 11;54(13):8051-61. doi: 10.1167/iovs.13-12844.
PMID: 24255046
citation: Sonawane S, Khanolkar V, Namavari A, Chaudhary S, Gandhi S, Tibrewal S, Jassim SH, Shaheen B, Hallak J, Horner JH, Newcomb M, Sarkar J, Jain S. Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm for inflammation in dry eye disease. Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8253-63. doi: 10.1167/iovs.12-10430.
PMID: 23169882
responsible party type: Principal Investigator
investigator affiliation: University of Illinois at Chicago
investigator full name: Sandeep Jain, MD
investigator title: Associate Professor of Ophthalmology
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Outcomes of this clinical trial shouldn't be over-interpreted for benefit. Accurate assessment of therapeutic implications of DNase eye drops will only be possible after adequately powered definitive pivotal trials. Small sample size is a limitation.
point of contact: 