<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/NCT03274999</url>
  </required_header>
  <id_info>
    <org_study_id>OCUN-020</org_study_id>
    <nct_id>NCT03274999</nct_id>
  </id_info>
  <brief_title>Clinical Study to Evaluate Tear Characteristics Following Acute TrueTear™ Use</brief_title>
  <official_title>Randomized, Controlled, Single-Center, Cross-Over Clinical Study to Evaluate Tear Characteristics Following Acute TrueTear™ Use</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Allergan</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the change in tear meniscus height (TMH) produced by intranasal&#xD;
      stimulation with TrueTear™ compared with the same device applied extranasally (control).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Based on interim review and decision to re-design the study.&#xD;
  </why_stopped>
  <start_date type="Actual">October 18, 2017</start_date>
  <completion_date type="Actual">November 9, 2017</completion_date>
  <primary_completion_date type="Actual">November 9, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline (Pre-application) in Tear Meniscus Height (TMH) at Eye Opening and Pre-Blink</measure>
    <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
    <description>Tear meniscus height is defined as the mean height of the lower tear prism to the edge of the eye lid measured by the investigator using the Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to time (T) T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 minutes (mins) after application was reported. A negative change from Baseline (Pre-application) indicates improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline (Pre-application) in Tear Lipid Layer Thickness at Eye Opening and Pre-Blink</measure>
    <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
    <description>Lipid layer thickness is defined as the average thickness of the lipid layer calculated from the thickness of the various pattern weighted by the relative coverage of each pattern measured by the investigator using the Tearscope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported. A negative change from Baseline (Pre-application) indicates improvement .</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline (Pre-application) in Non-Invasive Tear Film Break-Up Time (NIBUT)</measure>
    <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
    <description>Non-invasive break-up time is the time in seconds between eye opening and the appearance of the first visible break in the lipid layer of the pre-corneal tear film measured by the investigator using the Tearscope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported. A negative change from Baseline (Pre-application) indicates improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Pre-application in Protective Index (PI)</measure>
    <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
    <description>The Protected Index (PI) corresponds to the percentage of the corneal surface that is not exposed to the atmosphere (i.e. fully covered by the tear film) over the full interblink period measured by the investigator using a Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Pre-application in Exposed Area (EA)</measure>
    <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
    <description>Exposed Area is defined as the percentage of the observed area not covered by the tear film at the time of the blink hence exposed to the atmosphere measured by the investigator using a Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Dry Eye Syndromes</condition>
  <arm_group>
    <arm_group_label>TrueTear™ Intranasal then Extranasal Application</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 followed by TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 14.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TrueTear™ Extranasal then Intranasal Application</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 followed by TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 14.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>TrueTear™ Application</intervention_name>
    <description>Intranasal and extranasal application of TrueTear™ device for approximately 3 minutes at Day 0 and Day 14.</description>
    <arm_group_label>TrueTear™ Extranasal then Intranasal Application</arm_group_label>
    <arm_group_label>TrueTear™ Intranasal then Extranasal Application</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Baseline Ocular Surface Disease Index© (OSDI©) score of at least 23 with no more than&#xD;
             three responses of &quot;not applicable&quot;&#xD;
&#xD;
          -  In at least one eye, a baseline Schirmer test of ≤ 10 mm/5 minutes AND a cotton swab&#xD;
             nasal stimulation Schirmer test of at least 7 mm higher in the same eye&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic or recurrent epistaxis, coagulation disorders or other conditions that may&#xD;
             increase the risk of bleeding&#xD;
&#xD;
          -  History of nasal or sinus surgery&#xD;
&#xD;
          -  Vascularized polyp, deviated septum or severe nasal airway obstruction at the&#xD;
             Screening visit&#xD;
&#xD;
          -  Intraocular and extraocular surgery in either eye within three months of the Screening&#xD;
             Visit or refractive surgery within twelve months of the Screening Visit&#xD;
&#xD;
          -  Cardiac demand pacemaker, implanted defibrillator, or other active implanted metallic&#xD;
             or active implanted electronic device in the head&#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>Clinical Director</last_name>
    <role>Study Director</role>
    <affiliation>Allergan, plc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ocular Technology Group International</name>
      <address>
        <city>London</city>
        <zip>SW1E 6AU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://AllerganClinicalTrials.com</url>
    <description>For information to locate a study location near you, please visit AllerganClinicalTrials.com</description>
  </link>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <results_first_submitted>November 5, 2020</results_first_submitted>
  <results_first_submitted_qc>March 4, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 8, 2021</results_first_posted>
  <disposition_first_submitted>November 9, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>March 4, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 8, 2021</disposition_first_posted>
  <last_update_submitted>March 4, 2021</last_update_submitted>
  <last_update_submitted_qc>March 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2021</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>
  </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>August 9, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT03274999/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TrueTear™ Intranasal Then Extranasal Application</title>
          <description>TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 followed by TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 14.</description>
        </group>
        <group group_id="P2">
          <title>TrueTear™ Extranasal Then Intranasal Application</title>
          <description>TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 followed by TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 14.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention (Day 0)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Intervention (Day 14)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who received TrueTear™ either intranasally or extranasally.</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>All participants randomized to receive TrueTear™ device either intranasally (test) or extranasally (control) on Days 0 and 14.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>All participants randomized to receive TrueTear ™ device either intranasally or extranasally on Days 0 and 14.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52.4" spread="10.1"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <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="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline (Pre-application) in Tear Meniscus Height (TMH) at Eye Opening and Pre-Blink</title>
        <description>Tear meniscus height is defined as the mean height of the lower tear prism to the edge of the eye lid measured by the investigator using the Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to time (T) T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 minutes (mins) after application was reported. A negative change from Baseline (Pre-application) indicates improvement.</description>
        <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
        <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>TrueTear™ Extranasal Application</title>
            <description>TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
          <group group_id="O2">
            <title>TrueTear™ Intranasal Application</title>
            <description>TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Pre-application) in Tear Meniscus Height (TMH) at Eye Opening and Pre-Blink</title>
          <description>Tear meniscus height is defined as the mean height of the lower tear prism to the edge of the eye lid measured by the investigator using the Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to time (T) T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 minutes (mins) after application was reported. A negative change from Baseline (Pre-application) indicates improvement.</description>
          <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
          <units>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="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eye-opening,Pre-application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.312" spread="0.132"/>
                    <measurement group_id="O2" value="0.310" spread="0.143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T0 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.047" spread="0.205"/>
                    <measurement group_id="O2" value="0.105" spread="0.177"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T15 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.010" spread="0.110"/>
                    <measurement group_id="O2" value="0.002" spread="0.096"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T30 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.035" spread="0.118"/>
                    <measurement group_id="O2" value="-0.003" spread="0.100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T60 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.018" spread="0.107"/>
                    <measurement group_id="O2" value="-0.038" spread="0.092"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T120 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.021" spread="0.138"/>
                    <measurement group_id="O2" value="-0.039" spread="0.101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T180 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.049" spread="0.136"/>
                    <measurement group_id="O2" value="-0.032" spread="0.103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T240 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.022" spread="0.125"/>
                    <measurement group_id="O2" value="-0.033" spread="0.137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T300 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.055" spread="0.095"/>
                    <measurement group_id="O2" value="-0.065" spread="0.110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T360 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.049" spread="0.111"/>
                    <measurement group_id="O2" value="-0.060" spread="0.126"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Pre-application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.379" spread="0.152"/>
                    <measurement group_id="O2" value="0.350" spread="0.143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T0 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.067" spread="0.263"/>
                    <measurement group_id="O2" value="0.154" spread="0.231"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T15 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.005" spread="0.143"/>
                    <measurement group_id="O2" value="0.027" spread="0.097"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T30 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.040" spread="0.149"/>
                    <measurement group_id="O2" value="0.012" spread="0.105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T60 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.035" spread="0.159"/>
                    <measurement group_id="O2" value="-0.008" spread="0.097"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T120 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.050" spread="0.150"/>
                    <measurement group_id="O2" value="-0.024" spread="0.097"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T180 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.050" spread="0.153"/>
                    <measurement group_id="O2" value="-0.039" spread="0.074"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T240 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.018" spread="0.159"/>
                    <measurement group_id="O2" value="-0.037" spread="0.132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T300 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.074" spread="0.133"/>
                    <measurement group_id="O2" value="-0.070" spread="0.117"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T360 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.054" spread="0.121"/>
                    <measurement group_id="O2" value="-0.047" spread="0.129"/>
                  </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>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T0) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.156</p_value>
            <p_value_desc>Eye-opening, T0: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T15) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.395</p_value>
            <p_value_desc>Eye-opening, T15: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T30) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.114</p_value>
            <p_value_desc>Eye-opening, T30: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T60) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.211</p_value>
            <p_value_desc>Eye-opening, T60: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T120) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.332</p_value>
            <p_value_desc>Eye-opening, T120: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T180) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.318</p_value>
            <p_value_desc>Eye-opening, T180: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T240) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.375</p_value>
            <p_value_desc>Eye-opening, T240: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T300) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.352</p_value>
            <p_value_desc>Eye-opening, T300: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T360) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.312</p_value>
            <p_value_desc>Eye-opening, T360: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T0) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.134</p_value>
            <p_value_desc>Pre-blink, T0: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T15) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.315</p_value>
            <p_value_desc>Pre-blink, T15: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T30) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.071</p_value>
            <p_value_desc>Pre-blink, T30: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T60) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.260</p_value>
            <p_value_desc>Pre-blink, T60: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T120) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.264</p_value>
            <p_value_desc>Pre-blink, T120: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T180) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.381</p_value>
            <p_value_desc>Pre-blink, T180: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T240) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.249</p_value>
            <p_value_desc>Pre-blink, T240: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T300) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.451</p_value>
            <p_value_desc>Pre-blink, T300: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T360) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.393</p_value>
            <p_value_desc>Pre-blink, T360: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline (Pre-application) in Tear Lipid Layer Thickness at Eye Opening and Pre-Blink</title>
        <description>Lipid layer thickness is defined as the average thickness of the lipid layer calculated from the thickness of the various pattern weighted by the relative coverage of each pattern measured by the investigator using the Tearscope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported. A negative change from Baseline (Pre-application) indicates improvement .</description>
        <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
        <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>TrueTear™ Extranasal Application</title>
            <description>TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
          <group group_id="O2">
            <title>TrueTear™ Intranasal Application</title>
            <description>TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Pre-application) in Tear Lipid Layer Thickness at Eye Opening and Pre-Blink</title>
          <description>Lipid layer thickness is defined as the average thickness of the lipid layer calculated from the thickness of the various pattern weighted by the relative coverage of each pattern measured by the investigator using the Tearscope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported. A negative change from Baseline (Pre-application) indicates improvement .</description>
          <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
          <units>nm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eye-opening,Pre-application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.090" spread="12.185"/>
                    <measurement group_id="O2" value="33.541" spread="9.848"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T0 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.325" spread="19.890"/>
                    <measurement group_id="O2" value="25.255" spread="21.278"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T15 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.527" spread="16.680"/>
                    <measurement group_id="O2" value="6.154" spread="9.924"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T30 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.820" spread="14.292"/>
                    <measurement group_id="O2" value="6.944" spread="14.559"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T60 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.542" spread="17.665"/>
                    <measurement group_id="O2" value="6.174" spread="13.224"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T120 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.385" spread="16.423"/>
                    <measurement group_id="O2" value="-0.310" spread="11.519"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T180 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.766" spread="12.617"/>
                    <measurement group_id="O2" value="1.522" spread="9.387"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T240 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.815" spread="16.918"/>
                    <measurement group_id="O2" value="2.212" spread="9.965"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T300 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.481" spread="16.789"/>
                    <measurement group_id="O2" value="4.662" spread="12.366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eye-opening,Change at T360 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.210" spread="14.388"/>
                    <measurement group_id="O2" value="1.320" spread="9.393"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Pre-application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.498" spread="19.880"/>
                    <measurement group_id="O2" value="45.330" spread="18.124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T0 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.907" spread="19.689"/>
                    <measurement group_id="O2" value="23.203" spread="24.003"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T15 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.145" spread="17.824"/>
                    <measurement group_id="O2" value="4.018" spread="20.612"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T30 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.662" spread="17.007"/>
                    <measurement group_id="O2" value="-0.351" spread="19.049"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T60 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.246" spread="20.592"/>
                    <measurement group_id="O2" value="2.990" spread="19.916"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T120 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.684" spread="17.573"/>
                    <measurement group_id="O2" value="-3.939" spread="13.767"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T180 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.373" spread="14.149"/>
                    <measurement group_id="O2" value="-4.464" spread="10.932"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T240 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.033" spread="17.147"/>
                    <measurement group_id="O2" value="-4.381" spread="14.947"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T300 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.700" spread="20.157"/>
                    <measurement group_id="O2" value="1.725" spread="20.086"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-blink,Change at T360 after application,Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.730" spread="16.013"/>
                    <measurement group_id="O2" value="-4.863" spread="13.992"/>
                  </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>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T0) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.006</p_value>
            <p_value_desc>Eye-opening, T0: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T15) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.063</p_value>
            <p_value_desc>Eye-opening, T15: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T30) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <p_value_desc>Eye-opening, T30: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T60) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.089</p_value>
            <p_value_desc>Eye-opening, T60: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T120) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.112</p_value>
            <p_value_desc>Eye-opening, T120: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T180) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.16</p_value>
            <p_value_desc>Eye-opening, T180: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T240) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.077</p_value>
            <p_value_desc>Eye-opening, T240: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T300) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.157</p_value>
            <p_value_desc>Eye-opening, T300: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T360) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.111</p_value>
            <p_value_desc>Eye-opening, T360: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T0) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.040</p_value>
            <p_value_desc>Pre-blink, T0: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T15) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.241</p_value>
            <p_value_desc>Pre-blink, T15: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T30) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.284</p_value>
            <p_value_desc>Pre-blink, T30: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T60) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.313</p_value>
            <p_value_desc>Pre-blink, T60: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T120) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.433</p_value>
            <p_value_desc>Pre-blink, T120: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T180) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.406</p_value>
            <p_value_desc>Pre-blink, T180: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T240) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.318</p_value>
            <p_value_desc>Pre-blink, T240: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T300) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.499</p_value>
            <p_value_desc>Pre-blink, T300: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T360) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.390</p_value>
            <p_value_desc>Pre-blink, T360: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline (Pre-application) in Non-Invasive Tear Film Break-Up Time (NIBUT)</title>
        <description>Non-invasive break-up time is the time in seconds between eye opening and the appearance of the first visible break in the lipid layer of the pre-corneal tear film measured by the investigator using the Tearscope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported. A negative change from Baseline (Pre-application) indicates improvement.</description>
        <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
        <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>TrueTear™ Extranasal Application</title>
            <description>TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
          <group group_id="O2">
            <title>TrueTear™ Intranasal Application</title>
            <description>TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Pre-application) in Non-Invasive Tear Film Break-Up Time (NIBUT)</title>
          <description>Non-invasive break-up time is the time in seconds between eye opening and the appearance of the first visible break in the lipid layer of the pre-corneal tear film measured by the investigator using the Tearscope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported. A negative change from Baseline (Pre-application) indicates improvement.</description>
          <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</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="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.211" spread="23.626"/>
                    <measurement group_id="O2" value="10.536" spread="8.458"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T0 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.668" spread="16.857"/>
                    <measurement group_id="O2" value="4.784" spread="13.738"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T15 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.489" spread="15.788"/>
                    <measurement group_id="O2" value="0.835" spread="8.258"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T30 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.561" spread="19.045"/>
                    <measurement group_id="O2" value="-0.639" spread="7.272"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T60 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.951" spread="27.848"/>
                    <measurement group_id="O2" value="-0.954" spread="9.171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T120 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.128" spread="14.178"/>
                    <measurement group_id="O2" value="1.683" spread="7.172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T180 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.911" spread="20.700"/>
                    <measurement group_id="O2" value="-0.449" spread="6.029"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T240 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.525" spread="26.612"/>
                    <measurement group_id="O2" value="-0.787" spread="9.026"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T300 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.387" spread="15.805"/>
                    <measurement group_id="O2" value="-1.656" spread="5.560"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T360 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.509" spread="18.756"/>
                    <measurement group_id="O2" value="-0.722" spread="8.369"/>
                  </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>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T0) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.053</p_value>
            <p_value_desc>T0: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T15) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.206</p_value>
            <p_value_desc>T15: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T30) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.221</p_value>
            <p_value_desc>T30: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T60) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.126</p_value>
            <p_value_desc>T60: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T120) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.124</p_value>
            <p_value_desc>T120: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T180) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.167</p_value>
            <p_value_desc>T180: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T240) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.377</p_value>
            <p_value_desc>T240: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T300) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.397</p_value>
            <p_value_desc>T300: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T360) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.441</p_value>
            <p_value_desc>T360: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Pre-application in Protective Index (PI)</title>
        <description>The Protected Index (PI) corresponds to the percentage of the corneal surface that is not exposed to the atmosphere (i.e. fully covered by the tear film) over the full interblink period measured by the investigator using a Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported.</description>
        <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
        <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>TrueTear™ Extranasal Application</title>
            <description>TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
          <group group_id="O2">
            <title>TrueTear™ Intranasal Application</title>
            <description>TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Pre-application in Protective Index (PI)</title>
          <description>The Protected Index (PI) corresponds to the percentage of the corneal surface that is not exposed to the atmosphere (i.e. fully covered by the tear film) over the full interblink period measured by the investigator using a Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported.</description>
          <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
          <units>percentage of area covered by tear film</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.999" spread="0.004"/>
                    <measurement group_id="O2" value="98.797" spread="5.351"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T0 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.003" spread="0.015"/>
                    <measurement group_id="O2" value="1.200" spread="5.343"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T15 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.001"/>
                    <measurement group_id="O2" value="1.198" spread="5.352"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T30 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.009" spread="0.036"/>
                    <measurement group_id="O2" value="1.196" spread="5.352"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T60 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.007"/>
                    <measurement group_id="O2" value="1.196" spread="5.352"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T120 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.002"/>
                    <measurement group_id="O2" value="1.179" spread="5.260"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T180 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.001" spread="0.004"/>
                    <measurement group_id="O2" value="1.193" spread="5.353"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T240 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.005" spread="0.020"/>
                    <measurement group_id="O2" value="1.196" spread="5.352"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T300 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.004" spread="0.017"/>
                    <measurement group_id="O2" value="1.196" spread="5.352"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T360 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.003"/>
                    <measurement group_id="O2" value="1.198" spread="5.352"/>
                  </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>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T0) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.034</p_value>
            <p_value_desc>T0: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T15) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.143</p_value>
            <p_value_desc>T15: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T30) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.328</p_value>
            <p_value_desc>T30: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T60) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.250</p_value>
            <p_value_desc>T60: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T120) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.090</p_value>
            <p_value_desc>T120: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T180) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.328</p_value>
            <p_value_desc>T180: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T240) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.055</p_value>
            <p_value_desc>T240: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T300) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.090</p_value>
            <p_value_desc>T300: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T360) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.233</p_value>
            <p_value_desc>T360: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Pre-application in Exposed Area (EA)</title>
        <description>Exposed Area is defined as the percentage of the observed area not covered by the tear film at the time of the blink hence exposed to the atmosphere measured by the investigator using a Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported.</description>
        <time_frame>Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application</time_frame>
        <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>TrueTear™ Extranasal Application</title>
            <description>TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
          <group group_id="O2">
            <title>TrueTear™ Intranasal Application</title>
            <description>TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 or Day 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Pre-application in Exposed Area (EA)</title>
          <description>Exposed Area is defined as the percentage of the observed area not covered by the tear film at the time of the blink hence exposed to the atmosphere measured by the investigator using a Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported.</description>
          <population>All participants who met the eligibility criteria, adhered to the protocol, and successfully completed the full study assessment were included in the per-protocol analysis.</population>
          <units>percentage area not covered by tear film</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.005" spread="0.022"/>
                    <measurement group_id="O2" value="0.022" spread="0.057"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T0 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.014" spread="0.077"/>
                    <measurement group_id="O2" value="-0.014" spread="0.035"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T15 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.002" spread="0.010"/>
                    <measurement group_id="O2" value="-0.006" spread="0.046"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T30 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.033" spread="0.140"/>
                    <measurement group_id="O2" value="-0.008" spread="0.051"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T60 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.001" spread="0.029"/>
                    <measurement group_id="O2" value="0.001" spread="0.088"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T120 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.004" spread="0.016"/>
                    <measurement group_id="O2" value="0.028" spread="0.145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T180 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.005" spread="0.022"/>
                    <measurement group_id="O2" value="0.011" spread="0.086"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T240 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.012" spread="0.040"/>
                    <measurement group_id="O2" value="-0.008" spread="0.091"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T300 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.005" spread="0.022"/>
                    <measurement group_id="O2" value="-0.002" spread="0.052"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at T360 after application, Day 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.001" spread="0.018"/>
                    <measurement group_id="O2" value="-0.006" spread="0.051"/>
                  </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>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T0) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.072</p_value>
            <p_value_desc>T0: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T15) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.297</p_value>
            <p_value_desc>T15: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T30) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.328</p_value>
            <p_value_desc>T30: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T60) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.447</p_value>
            <p_value_desc>T60: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T120) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.328</p_value>
            <p_value_desc>T120: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T180) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.090</p_value>
            <p_value_desc>T180: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T240) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.055</p_value>
            <p_value_desc>T240: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T300) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.090</p_value>
            <p_value_desc>T300: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for the outcome measure is the difference in the change from the pre-application value at post-application time (T360) between the intranasal (test) and extranasal (control) applications are zero.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.500</p_value>
            <p_value_desc>T360: P-value was calculated using 1-sided paired t-test.</p_value_desc>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 0 up to Day 14</time_frame>
      <desc>Safety population included all participants that initiated at least one application.</desc>
      <group_list>
        <group group_id="E1">
          <title>TrueTear™ Extranasal Application</title>
          <description>TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 or Day 14.</description>
        </group>
        <group group_id="E2">
          <title>TrueTear™ Intranasal Application</title>
          <description>TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 or Day 14.</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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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 less than or equal to 90 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>Therapeutic Area, Head</name_or_title>
      <organization>Allergan</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/NCT03274999
org study id: OCUN-020
nct id: NCT03274999
lead sponsor: 
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This study will evaluate the change in tear meniscus height (TMH) produced by intranasal
      stimulation with TrueTear™ compared with the same device applied extranasally (control).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline (Pre-application) in Tear Meniscus Height (TMH) at Eye Opening and Pre-Blink
time frame: Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application
description: Tear meniscus height is defined as the mean height of the lower tear prism to the edge of the eye lid measured by the investigator using the Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to time (T) T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 minutes (mins) after application was reported. A negative change from Baseline (Pre-application) indicates improvement.
measure: Change From Baseline (Pre-application) in Tear Lipid Layer Thickness at Eye Opening and Pre-Blink
time frame: Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application
description: Lipid layer thickness is defined as the average thickness of the lipid layer calculated from the thickness of the various pattern weighted by the relative coverage of each pattern measured by the investigator using the Tearscope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported. A negative change from Baseline (Pre-application) indicates improvement .
measure: Change From Baseline (Pre-application) in Non-Invasive Tear Film Break-Up Time (NIBUT)
time frame: Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application
description: Non-invasive break-up time is the time in seconds between eye opening and the appearance of the first visible break in the lipid layer of the pre-corneal tear film measured by the investigator using the Tearscope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported. A negative change from Baseline (Pre-application) indicates improvement.
measure: Change From Pre-application in Protective Index (PI)
time frame: Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application
description: The Protected Index (PI) corresponds to the percentage of the corneal surface that is not exposed to the atmosphere (i.e. fully covered by the tear film) over the full interblink period measured by the investigator using a Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported.
measure: Change From Pre-application in Exposed Area (EA)
time frame: Pre-application (Day 0) to time (T) 0 (immediately), 15, 30, 60, 120, 180, 240, 300 and 360 minutes on Day 0 after application
description: Exposed Area is defined as the percentage of the observed area not covered by the tear film at the time of the blink hence exposed to the atmosphere measured by the investigator using a Tear scope Plus in conjunction with a Topcon SL-D7 slit lamp biomicroscope and high-resolution digital video recording. Change from Baseline to T0 (immediately), T15, T30, T60, T120, T180, T240, T300, T360 mins after application was reported.
arm group label: TrueTear™ Intranasal then Extranasal Application
arm group type: Experimental
description: TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 0 followed by TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 14.
arm group label: TrueTear™ Extranasal then Intranasal Application
arm group type: Experimental
description: TrueTear™ device, extranasal (control) application, for approximately 3 minutes on Day 0 followed by TrueTear™ device, intranasal (test) application, for approximately 3 minutes on Day 14.
intervention type: Device
intervention name: TrueTear™ Application
description: Intranasal and extranasal application of TrueTear™ device for approximately 3 minutes at Day 0 and Day 14.
arm group label: TrueTear™ Extranasal then Intranasal Application
arm group label: TrueTear™ Intranasal then Extranasal Application
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Director
role: Study Director
affiliation: Allergan, plc
facility: 
country: United Kingdom
url: http://AllerganClinicalTrials.com
description: For information to locate a study location near you, please visit AllerganClinicalTrials.com
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 