<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/NCT01664949</url>
  </required_header>
  <id_info>
    <org_study_id>11002X-001</org_study_id>
    <secondary_id>2012-002238-35</secondary_id>
    <nct_id>NCT01664949</nct_id>
  </id_info>
  <brief_title>A Study to Compare the Safety and Efficacy of A New Eye Drop Formulation With OPTIVE™ in Subjects With Dry Eye Disease</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Allergan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety and efficacy of a carboxymethylcellulose based eye drop&#xD;
      formulation compared with carboxymethylcellulose based preservative-free lubricant eye drops&#xD;
      (OPTIVE™) in subjects with dry eye disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">May 2014</primary_completion_date>
  <phase>Phase 3</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>Change From Baseline in Ocular Surface Disease Index (OSDI) Score at Day 90</measure>
    <time_frame>Baseline, Day 90</time_frame>
    <description>The OSDI consists of 12 questions to assess visual function, ocular symptoms and environmental triggers related to dry eye. Each of the 12 questions is assessed using a 5-point scale (0=none of the time; 4 = all of the time) which is converted to a total score between 0-100. OSDI total scores of 0-12=normal (best), 13-22= mild ocular surface disease, 23-32 =moderate ocular surface disease, and 33-100=severe ocular surface disease (worst). A negative number change from Baseline indicates improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Tear Break-up Time (TBUT)</measure>
    <time_frame>Baseline, Day 90</time_frame>
    <description>TBUT is the time in seconds for the tear film to visually break up after a complete blink. The average of 3 consecutive observations is reported for each participant. The longer it takes, the more stable the tear film. The eye with the shorter average TBUT at Baseline was used for analysis. A positive number change from Baseline indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Corneal Staining</measure>
    <time_frame>Baseline, Day 90</time_frame>
    <description>Staining of the cornea following ocular administration of fluorescein dye was graded using a 6-point scale (0=no staining, 5=diffuse staining). The eye with the higher score at Baseline was used for analysis. The higher the grade score, the worse the dry eye severity. A negative number change from Baseline indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Conjunctival Staining</measure>
    <time_frame>Baseline, Day 90</time_frame>
    <description>Staining of the conjunctiva following ocular administration of lissamine green dye was graded using a 6-point scale (0=no staining, 5=diffuse staining). Conjunctival staining has 2 zones, nasal and temporal, which are added together to provide the total staining score. The eye with the higher score at Baseline was used for analysis. The higher the grade score, the worse the dry eye severity. A negative number change from Baseline indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Schirmer Test</measure>
    <time_frame>Baseline, Day 90</time_frame>
    <description>The Schirmer's Test measures the rate of the secretion of tears produced by the eye over 5 minutes. The results indicate the presence of dry eye. The eye with the lower value at Baseline was used for Analysis. Normal = greater than or equal to 15 millimeters (mm) of tears, Dry Eye = less than 15 mm of tears.. The smaller the number, the more severe the dry eye. A positive number change from Baseline indicates improvement.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">460</enrollment>
  <condition>Dry Eye Disease</condition>
  <arm_group>
    <arm_group_label>Carboxymethylcellulose Based Eye Drop Formulation A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPTIVE™</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboxymethylcellulose Based Eye Drop Formulation A</intervention_name>
    <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
    <arm_group_label>Carboxymethylcellulose Based Eye Drop Formulation A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops</intervention_name>
    <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
    <arm_group_label>OPTIVE™</arm_group_label>
    <other_name>REFRESH OPTIVE™</other_name>
    <other_name>OPTAVA™</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have used artificial tears for dry eye&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Start date of over the counter, herbal, prescription or nutritional supplements that&#xD;
             may affect dry eye or vision within 3 months prior to study start or an anticipated&#xD;
             change in dosage during the study&#xD;
&#xD;
          -  History of eye surgery or trauma in the 6 months prior to study start&#xD;
&#xD;
          -  Current use or use within 2 weeks of study start, of topical eye medications.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Allergan</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tours Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Freiburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Padova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Parma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Huelva</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Southampton</city>
        <state>Hampshire</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Great Yarmouth</city>
        <state>Norfolk</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>August 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <results_first_submitted>May 22, 2015</results_first_submitted>
  <results_first_submitted_qc>May 22, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 8, 2015</results_first_posted>
  <last_update_submitted>September 8, 2015</last_update_submitted>
  <last_update_submitted_qc>September 8, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 21, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
    <mesh_term>Eye Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboxymethylcellulose Sodium</mesh_term>
    <mesh_term>Ophthalmic Solutions</mesh_term>
    <mesh_term>Lubricant Eye Drops</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Carboxymethylcellulose Based Eye Drop Formulation A</title>
          <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
        </group>
        <group group_id="P2">
          <title>OPTIVE™</title>
          <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 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="224"/>
                <participants group_id="P2" count="236"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="200"/>
                <participants group_id="P2" count="211"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Personal Reasons</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other Miscellaneous Reasons</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Carboxymethylcellulose Based Eye Drop Formulation A</title>
          <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
        </group>
        <group group_id="B2">
          <title>OPTIVE™</title>
          <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 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="224"/>
            <count group_id="B2" value="236"/>
            <count group_id="B3" value="460"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt; 30 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9" spread="13.77"/>
                    <measurement group_id="B2" value="10" spread="13.65"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 to 40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt; 40 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="200"/>
                    <measurement group_id="B2" value="211"/>
                    <measurement group_id="B3" value="411"/>
                  </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="182"/>
                    <measurement group_id="B2" value="189"/>
                    <measurement group_id="B3" value="371"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Ocular Surface Disease Index (OSDI) Score at Day 90</title>
        <description>The OSDI consists of 12 questions to assess visual function, ocular symptoms and environmental triggers related to dry eye. Each of the 12 questions is assessed using a 5-point scale (0=none of the time; 4 = all of the time) which is converted to a total score between 0-100. OSDI total scores of 0-12=normal (best), 13-22= mild ocular surface disease, 23-32 =moderate ocular surface disease, and 33-100=severe ocular surface disease (worst). A negative number change from Baseline indicates improvement.</description>
        <time_frame>Baseline, Day 90</time_frame>
        <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carboxymethylcellulose Based Eye Drop Formulation A</title>
            <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
          <group group_id="O2">
            <title>OPTIVE™</title>
            <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Ocular Surface Disease Index (OSDI) Score at Day 90</title>
          <description>The OSDI consists of 12 questions to assess visual function, ocular symptoms and environmental triggers related to dry eye. Each of the 12 questions is assessed using a 5-point scale (0=none of the time; 4 = all of the time) which is converted to a total score between 0-100. OSDI total scores of 0-12=normal (best), 13-22= mild ocular surface disease, 23-32 =moderate ocular surface disease, and 33-100=severe ocular surface disease (worst). A negative number change from Baseline indicates improvement.</description>
          <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
          <units>score 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="196"/>
                <count group_id="O2" value="198"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.77" spread="14.018"/>
                    <measurement group_id="O2" value="40.92" spread="13.310"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Day 90 (n=181,185)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.88" spread="17.496"/>
                    <measurement group_id="O2" value="-15.97" spread="16.146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Tear Break-up Time (TBUT)</title>
        <description>TBUT is the time in seconds for the tear film to visually break up after a complete blink. The average of 3 consecutive observations is reported for each participant. The longer it takes, the more stable the tear film. The eye with the shorter average TBUT at Baseline was used for analysis. A positive number change from Baseline indicates improvement.</description>
        <time_frame>Baseline, Day 90</time_frame>
        <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carboxymethylcellulose Based Eye Drop Formulation A</title>
            <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
          <group group_id="O2">
            <title>OPTIVE™</title>
            <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Tear Break-up Time (TBUT)</title>
          <description>TBUT is the time in seconds for the tear film to visually break up after a complete blink. The average of 3 consecutive observations is reported for each participant. The longer it takes, the more stable the tear film. The eye with the shorter average TBUT at Baseline was used for analysis. A positive number change from Baseline indicates improvement.</description>
          <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for 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="196"/>
                <count group_id="O2" value="198"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.50" spread="1.868"/>
                    <measurement group_id="O2" value="4.44" spread="1.894"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Day 90 (n=181,185)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.69" spread="5.167"/>
                    <measurement group_id="O2" value="2.24" spread="3.262"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Corneal Staining</title>
        <description>Staining of the cornea following ocular administration of fluorescein dye was graded using a 6-point scale (0=no staining, 5=diffuse staining). The eye with the higher score at Baseline was used for analysis. The higher the grade score, the worse the dry eye severity. A negative number change from Baseline indicates improvement.</description>
        <time_frame>Baseline, Day 90</time_frame>
        <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carboxymethylcellulose Based Eye Drop Formulation A</title>
            <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
          <group group_id="O2">
            <title>OPTIVE™</title>
            <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Corneal Staining</title>
          <description>Staining of the cornea following ocular administration of fluorescein dye was graded using a 6-point scale (0=no staining, 5=diffuse staining). The eye with the higher score at Baseline was used for analysis. The higher the grade score, the worse the dry eye severity. A negative number change from Baseline indicates improvement.</description>
          <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
          <units>score 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="196"/>
                <count group_id="O2" value="198"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="0.99"/>
                    <measurement group_id="O2" value="1.6" spread="0.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Day 90 (n= 182, 184)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="0.88"/>
                    <measurement group_id="O2" value="-0.9" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Conjunctival Staining</title>
        <description>Staining of the conjunctiva following ocular administration of lissamine green dye was graded using a 6-point scale (0=no staining, 5=diffuse staining). Conjunctival staining has 2 zones, nasal and temporal, which are added together to provide the total staining score. The eye with the higher score at Baseline was used for analysis. The higher the grade score, the worse the dry eye severity. A negative number change from Baseline indicates improvement.</description>
        <time_frame>Baseline, Day 90</time_frame>
        <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carboxymethylcellulose Based Eye Drop Formulation A</title>
            <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
          <group group_id="O2">
            <title>OPTIVE™</title>
            <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Conjunctival Staining</title>
          <description>Staining of the conjunctiva following ocular administration of lissamine green dye was graded using a 6-point scale (0=no staining, 5=diffuse staining). Conjunctival staining has 2 zones, nasal and temporal, which are added together to provide the total staining score. The eye with the higher score at Baseline was used for analysis. The higher the grade score, the worse the dry eye severity. A negative number change from Baseline indicates improvement.</description>
          <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
          <units>score 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="196"/>
                <count group_id="O2" value="198"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="1.70"/>
                    <measurement group_id="O2" value="3.0" spread="1.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Day 90 (n= 181, 185)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="1.57"/>
                    <measurement group_id="O2" value="-1.4" spread="1.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Schirmer Test</title>
        <description>The Schirmer's Test measures the rate of the secretion of tears produced by the eye over 5 minutes. The results indicate the presence of dry eye. The eye with the lower value at Baseline was used for Analysis. Normal = greater than or equal to 15 millimeters (mm) of tears, Dry Eye = less than 15 mm of tears.. The smaller the number, the more severe the dry eye. A positive number change from Baseline indicates improvement.</description>
        <time_frame>Baseline, Day 90</time_frame>
        <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Carboxymethylcellulose Based Eye Drop Formulation A</title>
            <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
          <group group_id="O2">
            <title>OPTIVE™</title>
            <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Schirmer Test</title>
          <description>The Schirmer's Test measures the rate of the secretion of tears produced by the eye over 5 minutes. The results indicate the presence of dry eye. The eye with the lower value at Baseline was used for Analysis. Normal = greater than or equal to 15 millimeters (mm) of tears, Dry Eye = less than 15 mm of tears.. The smaller the number, the more severe the dry eye. A positive number change from Baseline indicates improvement.</description>
          <population>Participants from the Per-protocol population, all randomized participants without any significant protocol violations, with data available for analysis.</population>
          <units>mm/5 minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="196"/>
                <count group_id="O2" value="198"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.29" spread="6.692"/>
                    <measurement group_id="O2" value="8.10" spread="5.888"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Day 90 (n=172,174)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.38" spread="6.933"/>
                    <measurement group_id="O2" value="1.53" spread="6.253"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Carboxymethylcellulose Based Eye Drop Formulation A</title>
          <description>Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
        </group>
        <group group_id="E2">
          <title>OPTIVE™</title>
          <description>Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.0</default_vocab>
        <default_assessment>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="5" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="236"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="236"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Vitello-intestinal duct remnant</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Sudden hearing loss</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anti-neutrophil cytoplasmic antibody positive vasculitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="236"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carotid artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Glomerulonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <description>Adverse Event male specific.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="236"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye irritation</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="236"/>
              </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, Inc</organization>
      <phone>714-246-4500</phone>
      <email>clinicaltrials@allergan.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01664949
org study id: 11002X-001
secondary id: 2012-002238-35
nct id: NCT01664949
lead sponsor: 
has dmc: No
This study will evaluate the safety and efficacy of a carboxymethylcellulose based eye drop
      formulation compared with carboxymethylcellulose based preservative-free lubricant eye drops
      (OPTIVE™) in subjects with dry eye disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Ocular Surface Disease Index (OSDI) Score at Day 90
time frame: Baseline, Day 90
description: The OSDI consists of 12 questions to assess visual function, ocular symptoms and environmental triggers related to dry eye. Each of the 12 questions is assessed using a 5-point scale (0=none of the time; 4 = all of the time) which is converted to a total score between 0-100. OSDI total scores of 0-12=normal (best), 13-22= mild ocular surface disease, 23-32 =moderate ocular surface disease, and 33-100=severe ocular surface disease (worst). A negative number change from Baseline indicates improvement.
measure: Change From Baseline in Tear Break-up Time (TBUT)
time frame: Baseline, Day 90
description: TBUT is the time in seconds for the tear film to visually break up after a complete blink. The average of 3 consecutive observations is reported for each participant. The longer it takes, the more stable the tear film. The eye with the shorter average TBUT at Baseline was used for analysis. A positive number change from Baseline indicates improvement.
measure: Change From Baseline in Corneal Staining
time frame: Baseline, Day 90
description: Staining of the cornea following ocular administration of fluorescein dye was graded using a 6-point scale (0=no staining, 5=diffuse staining). The eye with the higher score at Baseline was used for analysis. The higher the grade score, the worse the dry eye severity. A negative number change from Baseline indicates improvement.
measure: Change From Baseline in Conjunctival Staining
time frame: Baseline, Day 90
description: Staining of the conjunctiva following ocular administration of lissamine green dye was graded using a 6-point scale (0=no staining, 5=diffuse staining). Conjunctival staining has 2 zones, nasal and temporal, which are added together to provide the total staining score. The eye with the higher score at Baseline was used for analysis. The higher the grade score, the worse the dry eye severity. A negative number change from Baseline indicates improvement.
measure: Change From Baseline in the Schirmer Test
time frame: Baseline, Day 90
description: The Schirmer's Test measures the rate of the secretion of tears produced by the eye over 5 minutes. The results indicate the presence of dry eye. The eye with the lower value at Baseline was used for Analysis. Normal = greater than or equal to 15 millimeters (mm) of tears, Dry Eye = less than 15 mm of tears.. The smaller the number, the more severe the dry eye. A positive number change from Baseline indicates improvement.
arm group label: Carboxymethylcellulose Based Eye Drop Formulation A
arm group type: Experimental
description: Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.
arm group label: OPTIVE™
arm group type: Active Comparator
description: Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.
intervention type: Drug
intervention name: Carboxymethylcellulose Based Eye Drop Formulation A
description: Carboxymethylcellulose Based Eye Drop Formulation A 1-2 drops in each eye as needed at least 2 times daily for 90 days.
arm group label: Carboxymethylcellulose Based Eye Drop Formulation A
intervention type: Drug
intervention name: Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops
description: Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops (OPTIVE™) 1-2 drops in each eye as needed at least 2 times daily for 90 days.
arm group label: OPTIVE™
other name: REFRESH OPTIVE™
other name: OPTAVA™
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Allergan
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Belgium
country: France
country: Germany
country: Italy
country: Russian Federation
country: Spain
country: United Kingdom
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Eye Diseases
mesh term: Carboxymethylcellulose Sodium
mesh term: Ophthalmic Solutions
mesh term: Lubricant Eye Drops
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 