<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/NCT01733732</url>
  </required_header>
  <id_info>
    <org_study_id>A00976</org_study_id>
    <nct_id>NCT01733732</nct_id>
  </id_info>
  <brief_title>SYSTANE® BALANCE Symptoms (OSDI) &amp; Inflammatory Biomarkers</brief_title>
  <official_title>Study to Evaluate the Efficacy of SYSTANE® BALANCE in Reducing Symptoms and Inflammatory Biomarker Expression of HLA-DR and Tear Film Cytokines in Dry Eye Subjects With Lipid Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alcon Research</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alcon Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the ability of SYSTANE® BALANCE and SYSTANE® Gel to&#xD;
      improve comfort in subjects with dry eyes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>The Ocular Surface Disease Index (OSDI) is a 12-question validated questionnaire used to measure ocular symptoms, visual function, and environmental factors that may affect a patient's vision. The OSDI scoring scale ranges from 0 to 100. The lower the score, the more symptomatic relief from dry eye symptoms a patient experiences. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates a perceived improvement in ocular comfort.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) by Visit</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>BCVA (with spectacles or other visual corrective devices) was determined using an ETDRS or modified EDTRS chart and measured in logMAR (logarithm of the minimum angle of resolution). Baseline-adjusted logMAR values were tabulated; a negative number change from baseline indicates better visual acuity. Each eye was assessed individually. Both eyes contributed to the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Eyes With Normal Slit-lamp Assessment</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>An undilated slit lamp exam was performed to examine the regions of the eye: orbit/lids, conjunctiva, cornea, anterior chamber, iris and lens. Each region was graded normal or abnormal. The percentage of eyes with normal assessments by region is reported. Each eye was assessed individually. Both eyes were included in the tabulation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Meibomian Gland Expression</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>Meibomian gland expression (ie, pressing on the meibomian glands to excrete oil) was performed by the investigator during undilated slit lamp examination and graded on a 4-point scale where 0=normal, clear oil expressed and 3=congealed or no material expressed. Each eye was assessed individually. Both eyes contributed to the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Non-invasive Keratographic Tear Break up Time (NIKBUT) by Visit</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>NIKBUT (time required for dry spots to appear on the surface of the eye after blinking) was measured in seconds using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Tear Meniscus Height (TMH) by Visit</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>TMH (the distance between the line of reflection along the top of the tear prism to the edge of the eyelid) was measured in millimeters using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Ocular Surface Staining by Visit</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>Ocular surface staining (damage to the ocular surface) was assessed using non-toxic ophthalmic dye during slit-lamp review. Corneal and conjunctival staining were graded as per the National Eye Institute (NEI) pictorial scale. The ocular staining score ranges from 0 to 3. The lower the score, the less signs of dry eye disease a patient exhibits. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30</measure>
    <time_frame>Baseline (Day 0), Day 30</time_frame>
    <description>A tear sample was collected and cytokine (small proteins) levels were analyzed using a High Sensitive Human Cytokine MilliPlex kit and measured in picograms/milliliter (pg/mL). Baseline-adjusted scores were tabulated; a negative number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline for % HLA-DR Inflammatory Biomarker Expression at Day 30</measure>
    <time_frame>Baseline (Day 0), Day 30</time_frame>
    <description>Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. The number of cells expressing the inflammatory marker HLA-DR (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as HLA-DR score at Day 30 minus HLA-DR score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline mRNA for % HLA-DR and TNF-alpha Gene Expression at Day 30</measure>
    <time_frame>Baseline (Day 0), Day 30</time_frame>
    <description>Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. Total RNA was isolated. The number of cells expressing the inflammatory marker (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as score at Day 30 minus score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Dry Eye Status as Measured by the Schirmer's Test by Visit</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>Dry eye status was assessed using the Schirmer's test. The investigator placed a paper strip on the eye under the lower lid for a specified time period. The length of the strip wetted by the tears was measured in millimeters. Baseline-adjusted values were tabulated; a positive number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Intraocular Pressure (IOP) by Visit</measure>
    <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
    <description>IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Baseline-adjusted values were tabulated. Each eye was assessed individually. Both eyes contributed to the mean.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Dry Eye Syndrome</condition>
  <arm_group>
    <arm_group_label>Systane Balance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SYSTANE® BALANCE Lubricant Eye Drops, 1 drop in each eye 4 times a day for 30 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Systane Gel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>SYSTANE® Gel, 1 drop in each eye 4 times a day for 30 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>SYSTANE® BALANCE Lubricant Eye Drops</intervention_name>
    <arm_group_label>Systane Balance</arm_group_label>
    <other_name>SYSTANE® BALANCE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>SYSTANE® Gel</intervention_name>
    <arm_group_label>Systane Gel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Read, sign, and date the Informed Consent Document;&#xD;
&#xD;
          -  Must not have used any topical ocular drops for approximately 24 hours prior to Visit&#xD;
             1;&#xD;
&#xD;
          -  Meet the protocol-specified dry eye criteria at Screening Visit (Visit 1);&#xD;
&#xD;
          -  Intraocular pressure (IOP) less than or equal to 22 millimeters of mercury (mmHg) in&#xD;
             both eyes;&#xD;
&#xD;
          -  Other protocol-defined inclusion criteria may apply.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or evidence of ocular or intraocular surgery or serious trauma in either eye&#xD;
             within the past 6 months;&#xD;
&#xD;
          -  Current punctal occlusion of any type (e.g., collagen plugs, silicone plugs);&#xD;
&#xD;
          -  History or evidence of epithelial herpes simplex keratitis (dendritic keratitis);&#xD;
             vaccinia; active or recent varicella viral disease of the cornea and/or conjunctiva;&#xD;
             chronic bacterial disease of the cornea and/or conjunctiva and/or eyelids;&#xD;
             mycobacterial infection of the eye; and/or fungal disease of the eye;&#xD;
&#xD;
          -  Use of any concomitant topical ocular medications during the study period;&#xD;
&#xD;
          -  Currently using Restasis but unwilling to discontinue its use 1 month prior to&#xD;
             screening and for the entire study period;&#xD;
&#xD;
          -  Use of systemic medications that may contribute to dry eye unless on a stable dosing&#xD;
             regimen for a minimum of 30 days prior to Visit 1 and that remains stable throughout&#xD;
             the study;&#xD;
&#xD;
          -  Uncontrolled ocular conditions such as uveitis, glaucoma or any other ocular condition&#xD;
             that may preclude the safe administration of either drop under investigation;&#xD;
&#xD;
          -  Other protocol-defined exclusion criteria may apply.&#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>Abayomi Ogundele, PharmD</last_name>
    <role>Study Director</role>
    <affiliation>Alcon Research</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Penny A. Asbell, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>November 2013</verification_date>
  <study_first_submitted>November 21, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <results_first_submitted>October 29, 2014</results_first_submitted>
  <results_first_submitted_qc>October 31, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 4, 2014</results_first_posted>
  <last_update_submitted>May 31, 2018</last_update_submitted>
  <last_update_submitted_qc>May 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dry eye</keyword>
  <keyword>Lipid deficiency</keyword>
  <keyword>Inflammatory markers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ophthalmic Solutions</mesh_term>
    <mesh_term>Lubricant Eye Drops</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited from 1 study center located in the US.</recruitment_details>
      <pre_assignment_details>A total of 54 subjects were screened and randomized. This reporting group includes all randomized subjects (54).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Systane Balance</title>
          <description>One drop in each eye 4 times a day for 30 days</description>
        </group>
        <group group_id="P2">
          <title>Systane Gel</title>
          <description>One drop in each eye 4 times a day for 30 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not attend all study visits</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>This analysis group includes all randomized subjects.</population>
      <group_list>
        <group group_id="B1">
          <title>Systane Balance</title>
          <description>One drop in each eye 4 times a day for 30 days</description>
        </group>
        <group group_id="B2">
          <title>Systane Gel</title>
          <description>One drop in each eye 4 times a day for 30 days</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
            <count group_id="B2" value="27"/>
            <count group_id="B3" value="54"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.3" spread="14.5"/>
                    <measurement group_id="B2" value="63.8" spread="12.8"/>
                    <measurement group_id="B3" value="63.0" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit</title>
        <description>The Ocular Surface Disease Index (OSDI) is a 12-question validated questionnaire used to measure ocular symptoms, visual function, and environmental factors that may affect a patient's vision. The OSDI scoring scale ranges from 0 to 100. The lower the score, the more symptomatic relief from dry eye symptoms a patient experiences. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates a perceived improvement in ocular comfort.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of subjects with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit</title>
          <description>The Ocular Surface Disease Index (OSDI) is a 12-question validated questionnaire used to measure ocular symptoms, visual function, and environmental factors that may affect a patient's vision. The OSDI scoring scale ranges from 0 to 100. The lower the score, the more symptomatic relief from dry eye symptoms a patient experiences. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates a perceived improvement in ocular comfort.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of subjects with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at Day 14, n=25, 27</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.85" spread="18.19"/>
                    <measurement group_id="O2" value="-12.58" spread="19.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at Day 30, n=27, 27</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.23" spread="21.72"/>
                    <measurement group_id="O2" value="-16.74" spread="21.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) by Visit</title>
        <description>BCVA (with spectacles or other visual corrective devices) was determined using an ETDRS or modified EDTRS chart and measured in logMAR (logarithm of the minimum angle of resolution). Baseline-adjusted logMAR values were tabulated; a negative number change from baseline indicates better visual acuity. Each eye was assessed individually. Both eyes contributed to the mean.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) by Visit</title>
          <description>BCVA (with spectacles or other visual corrective devices) was determined using an ETDRS or modified EDTRS chart and measured in logMAR (logarithm of the minimum angle of resolution). Baseline-adjusted logMAR values were tabulated; a negative number change from baseline indicates better visual acuity. Each eye was assessed individually. Both eyes contributed to the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>LogMAR</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at Day 14, n=50, 53</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.06"/>
                    <measurement group_id="O2" value="-0.01" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at Day 30, n=54, 51</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.06"/>
                    <measurement group_id="O2" value="-0.02" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Eyes With Normal Slit-lamp Assessment</title>
        <description>An undilated slit lamp exam was performed to examine the regions of the eye: orbit/lids, conjunctiva, cornea, anterior chamber, iris and lens. Each region was graded normal or abnormal. The percentage of eyes with normal assessments by region is reported. Each eye was assessed individually. Both eyes were included in the tabulation.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. The actual sample size used in calculating the outcome measure may be smaller due to missing responses and/or visit attendance.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance, Day 0</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Balance, Day 14</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O3">
            <title>Systane Balance, Day 30</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O4">
            <title>Systane Gel, Day 0</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O5">
            <title>Systane Gel, Day 14</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O6">
            <title>Systane Gel, Day 30</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Eyes With Normal Slit-lamp Assessment</title>
          <description>An undilated slit lamp exam was performed to examine the regions of the eye: orbit/lids, conjunctiva, cornea, anterior chamber, iris and lens. Each region was graded normal or abnormal. The percentage of eyes with normal assessments by region is reported. Each eye was assessed individually. Both eyes were included in the tabulation.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. The actual sample size used in calculating the outcome measure may be smaller due to missing responses and/or visit attendance.</population>
          <units>percentage of eyes</units>
          <param>Number</param>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
                <count group_id="O3" value="27"/>
                <count group_id="O4" value="27"/>
                <count group_id="O5" value="27"/>
                <count group_id="O6" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="54"/>
                <count group_id="O5" value="54"/>
                <count group_id="O6" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Orbit / Lids</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                    <measurement group_id="O4" value="0.0"/>
                    <measurement group_id="O5" value="0.0"/>
                    <measurement group_id="O6" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Conjunctiva</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.6"/>
                    <measurement group_id="O2" value="96.0"/>
                    <measurement group_id="O3" value="96.3"/>
                    <measurement group_id="O4" value="96.3"/>
                    <measurement group_id="O5" value="100.0"/>
                    <measurement group_id="O6" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cornea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.6"/>
                    <measurement group_id="O2" value="92.0"/>
                    <measurement group_id="O3" value="92.6"/>
                    <measurement group_id="O4" value="92.6"/>
                    <measurement group_id="O5" value="92.6"/>
                    <measurement group_id="O6" value="92.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anterior chamber</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                    <measurement group_id="O2" value="100.0"/>
                    <measurement group_id="O3" value="100.0"/>
                    <measurement group_id="O4" value="100.0"/>
                    <measurement group_id="O5" value="100.0"/>
                    <measurement group_id="O6" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Iris</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.4"/>
                    <measurement group_id="O2" value="94.0"/>
                    <measurement group_id="O3" value="94.4"/>
                    <measurement group_id="O4" value="100.0"/>
                    <measurement group_id="O5" value="100.0"/>
                    <measurement group_id="O6" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lens</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.4"/>
                    <measurement group_id="O2" value="44.0"/>
                    <measurement group_id="O3" value="44.4"/>
                    <measurement group_id="O4" value="51.9"/>
                    <measurement group_id="O5" value="51.9"/>
                    <measurement group_id="O6" value="51.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Meibomian Gland Expression</title>
        <description>Meibomian gland expression (ie, pressing on the meibomian glands to excrete oil) was performed by the investigator during undilated slit lamp examination and graded on a 4-point scale where 0=normal, clear oil expressed and 3=congealed or no material expressed. Each eye was assessed individually. Both eyes contributed to the mean.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Meibomian Gland Expression</title>
          <description>Meibomian gland expression (ie, pressing on the meibomian glands to excrete oil) was performed by the investigator during undilated slit lamp examination and graded on a 4-point scale where 0=normal, clear oil expressed and 3=congealed or no material expressed. Each eye was assessed individually. Both eyes contributed to the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (Day 0), n=54, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="0.60"/>
                    <measurement group_id="O2" value="1.6" spread="0.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14, n=50, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" spread="0.59"/>
                    <measurement group_id="O2" value="1.3" spread="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 30, n=54, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" spread="0.59"/>
                    <measurement group_id="O2" value="1.3" spread="0.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Non-invasive Keratographic Tear Break up Time (NIKBUT) by Visit</title>
        <description>NIKBUT (time required for dry spots to appear on the surface of the eye after blinking) was measured in seconds using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Non-invasive Keratographic Tear Break up Time (NIKBUT) by Visit</title>
          <description>NIKBUT (time required for dry spots to appear on the surface of the eye after blinking) was measured in seconds using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at Day 14, n=45, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.587" spread="6.696"/>
                    <measurement group_id="O2" value="-0.325" spread="4.557"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at Day 30, n=49, 52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.914" spread="5.697"/>
                    <measurement group_id="O2" value="1.261" spread="6.633"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Tear Meniscus Height (TMH) by Visit</title>
        <description>TMH (the distance between the line of reflection along the top of the tear prism to the edge of the eyelid) was measured in millimeters using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Tear Meniscus Height (TMH) by Visit</title>
          <description>TMH (the distance between the line of reflection along the top of the tear prism to the edge of the eyelid) was measured in millimeters using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>millimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at Day 14, n=50, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.146" spread="0.165"/>
                    <measurement group_id="O2" value="0.089" spread="0.181"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at Day 30, n=54, 52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.140" spread="0.168"/>
                    <measurement group_id="O2" value="0.165" spread="0.242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Ocular Surface Staining by Visit</title>
        <description>Ocular surface staining (damage to the ocular surface) was assessed using non-toxic ophthalmic dye during slit-lamp review. Corneal and conjunctival staining were graded as per the National Eye Institute (NEI) pictorial scale. The ocular staining score ranges from 0 to 3. The lower the score, the less signs of dry eye disease a patient exhibits. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. The actual sample size used in calculating the outcome measure may be smaller due to missing responses and/or visit attendance.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance, Change From Baseline at Day 14</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Balance, Change From Baseline at Day 30</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O3">
            <title>Systane Gel, Change From Baseline at Day 14</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O4">
            <title>Systane Gel, Change From Baseline at Day 30</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Ocular Surface Staining by Visit</title>
          <description>Ocular surface staining (damage to the ocular surface) was assessed using non-toxic ophthalmic dye during slit-lamp review. Corneal and conjunctival staining were graded as per the National Eye Institute (NEI) pictorial scale. The ocular staining score ranges from 0 to 3. The lower the score, the less signs of dry eye disease a patient exhibits. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. The actual sample size used in calculating the outcome measure may be smaller due to missing responses and/or visit attendance.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="27"/>
                <count group_id="O3" value="27"/>
                <count group_id="O4" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="54"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Corneal staining</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="2.0"/>
                    <measurement group_id="O2" value="-0.9" spread="2.3"/>
                    <measurement group_id="O3" value="-1.3" spread="2.2"/>
                    <measurement group_id="O4" value="-1.6" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Conjunctival staining</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="1.4"/>
                    <measurement group_id="O2" value="-0.7" spread="1.4"/>
                    <measurement group_id="O3" value="-0.9" spread="1.5"/>
                    <measurement group_id="O4" value="-1.0" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30</title>
        <description>A tear sample was collected and cytokine (small proteins) levels were analyzed using a High Sensitive Human Cytokine MilliPlex kit and measured in picograms/milliliter (pg/mL). Baseline-adjusted scores were tabulated; a negative number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
        <time_frame>Baseline (Day 0), Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of subjects with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30</title>
          <description>A tear sample was collected and cytokine (small proteins) levels were analyzed using a High Sensitive Human Cytokine MilliPlex kit and measured in picograms/milliliter (pg/mL). Baseline-adjusted scores were tabulated; a negative number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of subjects with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IFN-gamma, n=24, 25</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.680" spread="14.366"/>
                    <measurement group_id="O2" value="15.146" spread="65.229"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1beta, n=24, 25</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.192" spread="1.161"/>
                    <measurement group_id="O2" value="0.335" spread="2.515"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6, n=24, 25</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.902" spread="5.009"/>
                    <measurement group_id="O2" value="0.735" spread="16.364"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNF-alpha, n=24, 25</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.058" spread="1.713"/>
                    <measurement group_id="O2" value="0.693" spread="5.727"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline for % HLA-DR Inflammatory Biomarker Expression at Day 30</title>
        <description>Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. The number of cells expressing the inflammatory marker HLA-DR (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as HLA-DR score at Day 30 minus HLA-DR score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.</description>
        <time_frame>Baseline (Day 0), Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline for % HLA-DR Inflammatory Biomarker Expression at Day 30</title>
          <description>Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. The number of cells expressing the inflammatory marker HLA-DR (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as HLA-DR score at Day 30 minus HLA-DR score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit.</population>
          <units>percentage of cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.751" spread="1.934"/>
                    <measurement group_id="O2" value="-0.300" spread="0.844"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline mRNA for % HLA-DR and TNF-alpha Gene Expression at Day 30</title>
        <description>Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. Total RNA was isolated. The number of cells expressing the inflammatory marker (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as score at Day 30 minus score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.</description>
        <time_frame>Baseline (Day 0), Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of subjects with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline mRNA for % HLA-DR and TNF-alpha Gene Expression at Day 30</title>
          <description>Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. Total RNA was isolated. The number of cells expressing the inflammatory marker (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as score at Day 30 minus score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of subjects with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>percentage of cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HLA-DR, n=19, 25</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.079" spread="2.199"/>
                    <measurement group_id="O2" value="0.019" spread="1.027"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNF-alpha, n=20, 23</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.061" spread="0.313"/>
                    <measurement group_id="O2" value="0.009" spread="0.140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Dry Eye Status as Measured by the Schirmer's Test by Visit</title>
        <description>Dry eye status was assessed using the Schirmer's test. The investigator placed a paper strip on the eye under the lower lid for a specified time period. The length of the strip wetted by the tears was measured in millimeters. Baseline-adjusted values were tabulated; a positive number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Dry Eye Status as Measured by the Schirmer's Test by Visit</title>
          <description>Dry eye status was assessed using the Schirmer's test. The investigator placed a paper strip on the eye under the lower lid for a specified time period. The length of the strip wetted by the tears was measured in millimeters. Baseline-adjusted values were tabulated; a positive number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>millimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at Day 14, n=50, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="7.0"/>
                    <measurement group_id="O2" value="2.8" spread="7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at Day 30, n=54, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="8.5"/>
                    <measurement group_id="O2" value="2.6" spread="8.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Intraocular Pressure (IOP) by Visit</title>
        <description>IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Baseline-adjusted values were tabulated. Each eye was assessed individually. Both eyes contributed to the mean.</description>
        <time_frame>Baseline (Day 0), Day 14, Day 30</time_frame>
        <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Systane Balance</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
          <group group_id="O2">
            <title>Systane Gel</title>
            <description>One drop in each eye 4 times a day for 30 days</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Intraocular Pressure (IOP) by Visit</title>
          <description>IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Baseline-adjusted values were tabulated. Each eye was assessed individually. Both eyes contributed to the mean.</description>
          <population>This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, &quot;n&quot; is the number of eyes with non-missing values at the specific time point for each arm group, respectively.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at Day 14, n=50, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.5"/>
                    <measurement group_id="O2" value="0.2" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at Day 30, n=54, 54</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="1.4"/>
                    <measurement group_id="O2" value="-0.1" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events (AEs) were collected for the duration of the study (7 months). This analysis group includes all subjects exposed to the test product.</time_frame>
      <desc>An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Reports of AEs were obtained through volunteered and elicited comments from the subjects.</desc>
      <group_list>
        <group group_id="E1">
          <title>Systane Balance</title>
          <description>One drop in each eye 4 times a day for 30 days</description>
        </group>
        <group group_id="E2">
          <title>Systane Gel</title>
          <description>One drop in each eye 4 times a day for 30 days</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 16.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metastasis to central nervous system</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Convulsion</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="27"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
              </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>Sponsor reserves the right of prior review of any publication or presentation of information related to the study.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Abayomi Ogundele, Pharm.D, Global Brand Medical Affairs Lead</name_or_title>
      <organization>Alcon Research, Ltd.</organization>
      <phone>1-888-451-3937</phone>
      <email>alcon.medinfo@alcon.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/NCT01733732
org study id: A00976
nct id: NCT01733732
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the ability of SYSTANE® BALANCE and SYSTANE® Gel to
      improve comfort in subjects with dry eyes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit
time frame: Baseline (Day 0), Day 14, Day 30
description: The Ocular Surface Disease Index (OSDI) is a 12-question validated questionnaire used to measure ocular symptoms, visual function, and environmental factors that may affect a patient's vision. The OSDI scoring scale ranges from 0 to 100. The lower the score, the more symptomatic relief from dry eye symptoms a patient experiences. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates a perceived improvement in ocular comfort.
measure: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) by Visit
time frame: Baseline (Day 0), Day 14, Day 30
description: BCVA (with spectacles or other visual corrective devices) was determined using an ETDRS or modified EDTRS chart and measured in logMAR (logarithm of the minimum angle of resolution). Baseline-adjusted logMAR values were tabulated; a negative number change from baseline indicates better visual acuity. Each eye was assessed individually. Both eyes contributed to the mean.
measure: Percentage of Eyes With Normal Slit-lamp Assessment
time frame: Baseline (Day 0), Day 14, Day 30
description: An undilated slit lamp exam was performed to examine the regions of the eye: orbit/lids, conjunctiva, cornea, anterior chamber, iris and lens. Each region was graded normal or abnormal. The percentage of eyes with normal assessments by region is reported. Each eye was assessed individually. Both eyes were included in the tabulation.
measure: Meibomian Gland Expression
time frame: Baseline (Day 0), Day 14, Day 30
description: Meibomian gland expression (ie, pressing on the meibomian glands to excrete oil) was performed by the investigator during undilated slit lamp examination and graded on a 4-point scale where 0=normal, clear oil expressed and 3=congealed or no material expressed. Each eye was assessed individually. Both eyes contributed to the mean.
measure: Mean Change From Baseline in Non-invasive Keratographic Tear Break up Time (NIKBUT) by Visit
time frame: Baseline (Day 0), Day 14, Day 30
description: NIKBUT (time required for dry spots to appear on the surface of the eye after blinking) was measured in seconds using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.
measure: Mean Change From Baseline in Tear Meniscus Height (TMH) by Visit
time frame: Baseline (Day 0), Day 14, Day 30
description: TMH (the distance between the line of reflection along the top of the tear prism to the edge of the eyelid) was measured in millimeters using the Oculus keratograph 5M. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.
measure: Mean Change From Baseline in Ocular Surface Staining by Visit
time frame: Baseline (Day 0), Day 14, Day 30
description: Ocular surface staining (damage to the ocular surface) was assessed using non-toxic ophthalmic dye during slit-lamp review. Corneal and conjunctival staining were graded as per the National Eye Institute (NEI) pictorial scale. The ocular staining score ranges from 0 to 3. The lower the score, the less signs of dry eye disease a patient exhibits. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.
measure: Mean Change From Baseline in Tear Inflammatory Cytokine Expression at Day 30
time frame: Baseline (Day 0), Day 30
description: A tear sample was collected and cytokine (small proteins) levels were analyzed using a High Sensitive Human Cytokine MilliPlex kit and measured in picograms/milliliter (pg/mL). Baseline-adjusted scores were tabulated; a negative number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.
measure: Mean Change From Baseline for % HLA-DR Inflammatory Biomarker Expression at Day 30
time frame: Baseline (Day 0), Day 30
description: Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. The number of cells expressing the inflammatory marker HLA-DR (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as HLA-DR score at Day 30 minus HLA-DR score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.
measure: Mean Change From Baseline mRNA for % HLA-DR and TNF-alpha Gene Expression at Day 30
time frame: Baseline (Day 0), Day 30
description: Conjunctival samples were collected by Impression Cytology (IC) and analyzed in a lab. Total RNA was isolated. The number of cells expressing the inflammatory marker (as a percentage of total cells) was calculated. Baseline-adjusted scores were calculated as score at Day 30 minus score at baseline. A negative baseline-adjusted value indicates an improvement. Each eye was assessed individually. Both eyes were included in the mean.
measure: Mean Change From Baseline in Dry Eye Status as Measured by the Schirmer's Test by Visit
time frame: Baseline (Day 0), Day 14, Day 30
description: Dry eye status was assessed using the Schirmer's test. The investigator placed a paper strip on the eye under the lower lid for a specified time period. The length of the strip wetted by the tears was measured in millimeters. Baseline-adjusted values were tabulated; a positive number change from baseline indicates an improvement. Each eye was assessed individually. Both eyes contributed to the mean.
measure: Mean Change From Baseline in Intraocular Pressure (IOP) by Visit
time frame: Baseline (Day 0), Day 14, Day 30
description: IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Baseline-adjusted values were tabulated. Each eye was assessed individually. Both eyes contributed to the mean.
arm group label: Systane Balance
arm group type: Experimental
description: SYSTANE® BALANCE Lubricant Eye Drops, 1 drop in each eye 4 times a day for 30 days
arm group label: Systane Gel
arm group type: Active Comparator
description: SYSTANE® Gel, 1 drop in each eye 4 times a day for 30 days
intervention type: Other
intervention name: SYSTANE® BALANCE Lubricant Eye Drops
arm group label: Systane Balance
other name: SYSTANE® BALANCE
intervention type: Other
intervention name: SYSTANE® Gel
arm group label: Systane Gel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Abayomi Ogundele, PharmD
role: Study Director
affiliation: Alcon Research
last name: Penny A. Asbell, MD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
country: United States
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Ophthalmic Solutions
mesh term: Lubricant Eye Drops
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 