<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/NCT01660256</url>
  </required_header>
  <id_info>
    <org_study_id>037E-11-003</org_study_id>
    <secondary_id>JapicCTI-121920</secondary_id>
    <nct_id>NCT01660256</nct_id>
  </id_info>
  <brief_title>Confirmatory Study of OPC-12759 Ophthalmic Solution</brief_title>
  <official_title>Confirmatory Study of OPC-12759 Ophthalmic Solution in Patients With Dry Eye</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Otsuka Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Otsuka Pharmaceutical Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to verify whether OPC-12759 ophthalmic solution is effective&#xD;
      compared with placebo in dry eye patients. OPC-12759 ophthalmic suspension will be used as a&#xD;
      reference drug.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">March 2013</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Fluorescein Corneal Staining (FCS) Score From Baseline</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>FCS indicates the damage to the corneal epithelium. Per the National Eye Institute/Industry Workshop report, the cornea was divided into 5 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-15). 0 is better.&#xD;
Changes of the FCS score from baseline to the last dose (last observation carried forward [LOCF]) were compared between 2% OPC-12759 ophthalmic solution and placebo by the t-test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>LGCS indicates the damage to the conjunctival epithelium. Per the National Eye Institute/Industry Workshop report, the conjunctiva was divided into 6 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-18). 0 is better.&#xD;
The scores and change from baseline at each examination (including LOCF) were compared between 2% OPC-12759 ophthalmic solution and placebo ophthalmic solution.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">209</enrollment>
  <condition>Dry Eye</condition>
  <arm_group>
    <arm_group_label>OPC-12759 ophthalmic solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OPC-12759 ophthalmic solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>OPC-12759 ophthalmic solution 0%</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OPC-12759 ophthalmic suspension</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>OPC-12759 ophthalmic suspension</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OPC-12759</intervention_name>
    <description>Instillation, 4 times/day for 4 weeks</description>
    <arm_group_label>OPC-12759 ophthalmic solution</arm_group_label>
    <arm_group_label>OPC-12759 ophthalmic suspension</arm_group_label>
    <other_name>rebamipide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Out patient&#xD;
&#xD;
          2. Subjective complaint of dry eye that has been present for minimum 20 months&#xD;
&#xD;
          3. Ocular discomfort severity is moderate to severe&#xD;
&#xD;
          4. Corneal - conjunctival damage is moderate to severe&#xD;
&#xD;
          5. Unanesthetized Schirmer's test score of 5mm/5minutes or less&#xD;
&#xD;
          6. Best corrected visual acuity of 0.2 or better in both eyes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of anterior segment disease or disorder other than that associated with dry&#xD;
             eye&#xD;
&#xD;
          2. Ocular hypertension patient or glaucoma patient with ophthalmic solution&#xD;
&#xD;
          3. Anticipated use of any topically-instilled ocular medications or patients who cannot&#xD;
             discontinue the use during the study&#xD;
&#xD;
          4. Anticipated use of contact lens during the study&#xD;
&#xD;
          5. Patient with punctal plug&#xD;
&#xD;
          6. Any history of ocular surgery within 12 months&#xD;
&#xD;
          7. Female patients who are pregnant,possibly pregnant or breast feeding&#xD;
&#xD;
          8. Known hypersensitivity to any component of the study drug or procedural medications&#xD;
&#xD;
          9. Receipt of any investigational product within 4 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eiji Murakami</last_name>
    <role>Study Director</role>
    <affiliation>Director of Division Dermatilogicals and Ophtalmolgicals, Otsuka Pharmaceutical Co., Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kansai Region</name>
      <address>
        <city>Kansai Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kanto region</name>
      <address>
        <city>Kanto Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyushu region</name>
      <address>
        <city>Kyushu Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokai region</name>
      <address>
        <city>Tokai Region</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>August 6, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2012</study_first_posted>
  <results_first_submitted>March 17, 2021</results_first_submitted>
  <results_first_submitted_qc>April 12, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 5, 2021</results_first_posted>
  <last_update_submitted>April 12, 2021</last_update_submitted>
  <last_update_submitted_qc>April 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rebamipide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>OPC-12759 Solution</title>
          <description>One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
        <group group_id="P3">
          <title>OPC-12759 Suspension</title>
          <description>One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="84"/>
                <participants group_id="P2" count="83"/>
                <participants group_id="P3" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="79"/>
                <participants group_id="P2" count="83"/>
                <participants group_id="P3" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>OPC-12759 Solution</title>
          <description>One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
        <group group_id="B3">
          <title>OPC-12759 Suspension</title>
          <description>One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
        <group group_id="B4">
          <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="84"/>
            <count group_id="B2" value="83"/>
            <count group_id="B3" value="42"/>
            <count group_id="B4" value="209"/>
          </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="57.7" spread="18.6"/>
                    <measurement group_id="B2" value="56.5" spread="16.6"/>
                    <measurement group_id="B3" value="54.2" spread="16.8"/>
                    <measurement group_id="B4" value="56.5" spread="17.4"/>
                  </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="74"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="35"/>
                    <measurement group_id="B4" value="176"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Japan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="84"/>
                    <measurement group_id="B2" value="83"/>
                    <measurement group_id="B3" value="42"/>
                    <measurement group_id="B4" value="209"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Fluorescein Corneal Staining (FCS) Score From Baseline</title>
        <description>FCS indicates the damage to the corneal epithelium. Per the National Eye Institute/Industry Workshop report, the cornea was divided into 5 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-15). 0 is better.&#xD;
Changes of the FCS score from baseline to the last dose (last observation carried forward [LOCF]) were compared between 2% OPC-12759 ophthalmic solution and placebo by the t-test.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <population>Full analysis set consisted of all subjects who had received the investigational product at least once after randomized assignment to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>OPC-12759 Solution</title>
            <description>One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>OPC-12759 Suspension</title>
            <description>One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fluorescein Corneal Staining (FCS) Score From Baseline</title>
          <description>FCS indicates the damage to the corneal epithelium. Per the National Eye Institute/Industry Workshop report, the cornea was divided into 5 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-15). 0 is better.&#xD;
Changes of the FCS score from baseline to the last dose (last observation carried forward [LOCF]) were compared between 2% OPC-12759 ophthalmic solution and placebo by the t-test.</description>
          <population>Full analysis set consisted of all subjects who had received the investigational product at least once after randomized assignment to a treatment group.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
                <count group_id="O2" value="83"/>
                <count group_id="O3" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.3" spread="0.2"/>
                    <measurement group_id="O2" value="-2.0" spread="0.3"/>
                    <measurement group_id="O3" value="-2.9" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.3</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline</title>
        <description>LGCS indicates the damage to the conjunctival epithelium. Per the National Eye Institute/Industry Workshop report, the conjunctiva was divided into 6 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-18). 0 is better.&#xD;
The scores and change from baseline at each examination (including LOCF) were compared between 2% OPC-12759 ophthalmic solution and placebo ophthalmic solution.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <population>Full analysis set consisted of all subjects who had received the investigational product at least once after randomized assignment to a treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>OPC-12759 Solution</title>
            <description>One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
          </group>
          <group group_id="O3">
            <title>OPC-12759 Suspension</title>
            <description>One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline</title>
          <description>LGCS indicates the damage to the conjunctival epithelium. Per the National Eye Institute/Industry Workshop report, the conjunctiva was divided into 6 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-18). 0 is better.&#xD;
The scores and change from baseline at each examination (including LOCF) were compared between 2% OPC-12759 ophthalmic solution and placebo ophthalmic solution.</description>
          <population>Full analysis set consisted of all subjects who had received the investigational product at least once after randomized assignment to a treatment group.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
                <count group_id="O2" value="83"/>
                <count group_id="O3" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.2" spread="0.3"/>
                    <measurement group_id="O2" value="-1.7" spread="0.3"/>
                    <measurement group_id="O3" value="-3.1" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.5</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment period (4 weeks)</time_frame>
      <desc>Only adverse events that occurred after the start of study treatment were evaluated.&#xD;
Safety analysis set consisted of all subjects who had received the investigational product at least once.</desc>
      <group_list>
        <group group_id="E1">
          <title>OPC-12759 Solution</title>
          <description>One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
        <group group_id="E3">
          <title>OPC-12759 Suspension</title>
          <description>One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>MedDRA Ver. 15.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal sensation in eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Eye irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Ocular discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Ulcerative keratitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Periproctitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Adenoviral conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Glucose urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Protein urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adenoma benign</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="84"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="42"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Trials</name_or_title>
      <organization>Otsuka Pharmaceutical Co., LTD.</organization>
      <phone>+81-3-6361-7366</phone>
      <email>CL_OPCJ_RDA_Team@otsuka.jp</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/NCT01660256
org study id: 037E-11-003
secondary id: JapicCTI-121920
nct id: NCT01660256
lead sponsor: 
has dmc: No
The purpose of this study is to verify whether OPC-12759 ophthalmic solution is effective
      compared with placebo in dry eye patients. OPC-12759 ophthalmic suspension will be used as a
      reference drug.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change in Fluorescein Corneal Staining (FCS) Score From Baseline
time frame: Baseline, Week 4
description: FCS indicates the damage to the corneal epithelium. Per the National Eye Institute/Industry Workshop report, the cornea was divided into 5 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-15). 0 is better.
Changes of the FCS score from baseline to the last dose (last observation carried forward [LOCF]) were compared between 2% OPC-12759 ophthalmic solution and placebo by the t-test.
measure: Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline
time frame: Baseline, Week 4
description: LGCS indicates the damage to the conjunctival epithelium. Per the National Eye Institute/Industry Workshop report, the conjunctiva was divided into 6 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-18). 0 is better.
The scores and change from baseline at each examination (including LOCF) were compared between 2% OPC-12759 ophthalmic solution and placebo ophthalmic solution.
arm group label: OPC-12759 ophthalmic solution
arm group type: Experimental
description: OPC-12759 ophthalmic solution
arm group label: Placebo
arm group type: Placebo Comparator
description: OPC-12759 ophthalmic solution 0%
arm group label: OPC-12759 ophthalmic suspension
arm group type: Active Comparator
description: OPC-12759 ophthalmic suspension
intervention type: Drug
intervention name: OPC-12759
description: Instillation, 4 times/day for 4 weeks
arm group label: OPC-12759 ophthalmic solution
arm group label: OPC-12759 ophthalmic suspension
other name: rebamipide
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Eiji Murakami
role: Study Director
affiliation: Director of Division Dermatilogicals and Ophtalmolgicals, Otsuka Pharmaceutical Co., Ltd.
facility: 
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Rebamipide
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 