<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/NCT02188160</url>
  </required_header>
  <id_info>
    <org_study_id>KPI-121-C-002</org_study_id>
    <nct_id>NCT02188160</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of KPI-121 in Subjects With Dry Eye Disease</brief_title>
  <acronym>Kauai</acronym>
  <official_title>A Phase II, Double-Masked, Randomized, Controlled Study of KPI-121 0.25% Ophthalmic Suspension Compared to Vehicle in Subjects With Dry Eye Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kala Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kala Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of this study is to determine the efficacy and safety of KPI-121 0.25%&#xD;
      ophthalmic suspension compared to vehicle (placebo) in subjects who have a documented&#xD;
      clinical diagnosis of dry eye disease. The product will be studied over 28 days, with 1-2&#xD;
      drops instilled in each eye four times daily (QID).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase II, multi-center, double-masked, randomized, vehicle-controlled,&#xD;
      parallel-group study designed to evaluate the safety and efficacy of KPI-121 0.25% ophthalmic&#xD;
      suspension versus vehicle in subjects with dry eye disease.&#xD;
&#xD;
      Approximately 400 subjects will be screened and up to 150 subjects will be randomized at up&#xD;
      to 12 centers located in the United States. Subjects will be randomized to 1 of 2 study arms&#xD;
      in an approximate 1:1 ratio. The study arms are: 1) KPI-121 0.25% ophthalmic suspension&#xD;
      administered 1-2 drops in each eye QID for up to 28 days or 2) vehicle administered as 1-2&#xD;
      drops in each eye QID for up to 28 days.&#xD;
&#xD;
      This study will include up to 6 clinic visits over 6 weeks. At Visit 1 Screening (14 ± 1 days&#xD;
      prior to Day 1), subjects who meet screening inclusion/exclusion criteria will begin a 2-week&#xD;
      run-in period during which they will be treated with 1-2 drops of single-masked vehicle in&#xD;
      each eye QID for 14 ± 1 days.&#xD;
&#xD;
      At Visit 2, Randomization (Day 1), subjects who continue to meet inclusion/exclusion criteria&#xD;
      will be eligible for randomization to 1 of the 2 arms of the study (i.e., KPI-121 0.25%&#xD;
      ophthalmic suspension or vehicle). Following randomization, subjects will be instructed to&#xD;
      return to the clinic to have a complete study evaluation at Study Visits 4 and 6 (Days 15 ± 1&#xD;
      day and 29 ± 1 day, respectively). Subjects will further be instructed to return to the&#xD;
      clinic for diary collection and in-clinic symptom assessment only at Visits 3 and 5 (Days 8 ±&#xD;
      1 day and 22 ± 1 day, respectively). The last dose of investigational product and the final&#xD;
      study visit will occur upon completion of 28 ± 1 days of exposure to investigational product.&#xD;
      Subjects will be released from the study at the end of Visit 6 (Day 29 ± 1 day).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bulbar Conjunctival Hyperemia</measure>
    <time_frame>Visit 6 (Day 29)</time_frame>
    <description>Comparison of mean bulbar conjunctival hyperemia in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ocular Discomfort</measure>
    <time_frame>Visit 6 (Day 29)</time_frame>
    <description>Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Corneal Fluorescein Staining Scores</measure>
    <time_frame>Visit 4 (Day 15) and Visit 6 (Day 29)</time_frame>
    <description>Comparison of mean corneal fluorescein staining scores in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe. The total score is obtained by summing each of the 5 sections of the cornea. The NEI score will be from 0-15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bulbar Conjunctival Hyperemia Scores</measure>
    <time_frame>Visit 4 (Day 15)</time_frame>
    <description>Comparison of mean bulbar conjunctival hyperemia scores in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ocular Discomfort</measure>
    <time_frame>Visit 4 (Day 15)</time_frame>
    <description>Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Dry Eye Syndromes</condition>
  <condition>Keratoconjunctivitis Sicca</condition>
  <arm_group>
    <arm_group_label>KPI-121 0.25% Ophthalmic Suspension</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vehicle</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KPI-121</intervention_name>
    <description>KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
    <arm_group_label>KPI-121 0.25% Ophthalmic Suspension</arm_group_label>
    <other_name>KPI-121 0.25% Ophthalmic Suspension</other_name>
    <other_name>Loteprednol etabonate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</description>
    <arm_group_label>Vehicle</arm_group_label>
    <other_name>Vehicle of KPI-121 0.25% Ophthalmic Suspension</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • Have a documented clinical diagnosis of dry eye disease in both eyes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity/contraindication to study product(s) or components.&#xD;
&#xD;
          -  History of glaucoma, IOP &gt;21 mmHg at the screening or randomization visits, or being&#xD;
             treated for glaucoma in either eye.&#xD;
&#xD;
          -  Diagnosis of: ongoing ocular infection; severe/serious ocular condition that in&#xD;
             judgment of Investigator could confound study assessments or limit compliance;&#xD;
             severe/serious systemic disease or uncontrolled medical condition that in judgment of&#xD;
             Investigator could confound study assessments or limit compliance; or have been&#xD;
             exposed to an investigational drug within the 30 days prior to screening.&#xD;
&#xD;
          -  In the opinion of Investigator or study coordinator, be unwilling or unable to comply&#xD;
             with study protocol or unable to successfully instill eye drops.&#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>Gregg Berdy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ophthalmology Associates</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Evans, OD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Total Eye Care, PA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kathy Kelley, OD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Price Vision Group</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Joseph Martel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Martel Eye Medical Group</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mark Milner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Eye Center of Southern CT, P.C.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steven Rauchman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>North Valley Eye Medical Group</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kenneth Sall, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sall Research Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeffrey Whitsett, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Whitsett Vision Group</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marc Abrams, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Abrams Eye Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael Korenfeld, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ecomprehensive Eye Care, Ltd / Vision Research Institute LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jodi Luchs, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>South Shore Eye Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sall Research Medical Center</name>
      <address>
        <city>Artesia</city>
        <state>California</state>
        <zip>90701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Valley Eye Medical Group</name>
      <address>
        <city>Mission Hills</city>
        <state>California</state>
        <zip>91345</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martel Eye Medical Group</name>
      <address>
        <city>Rancho Cordova</city>
        <state>California</state>
        <zip>95670</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Center of Southern CT, P.C.</name>
      <address>
        <city>Hamden</city>
        <state>Connecticut</state>
        <zip>06518</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Price Vision Group</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ophthalmology Associates</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Eye Care, Ltd. / Vision Research Institute, LLC</name>
      <address>
        <city>Washington</city>
        <state>Missouri</state>
        <zip>63090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Shore Eye Center, LLP</name>
      <address>
        <city>Wantagh</city>
        <state>New York</state>
        <zip>11793</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abrams Eye Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Total Eye Care, PA</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Whitsett Vision Group</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>July 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <results_first_submitted>November 25, 2020</results_first_submitted>
  <results_first_submitted_qc>January 4, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 6, 2021</results_first_posted>
  <disposition_first_submitted>July 8, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>July 8, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">July 12, 2016</disposition_first_posted>
  <last_update_submitted>January 4, 2021</last_update_submitted>
  <last_update_submitted_qc>January 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pain</keyword>
  <keyword>Corticosteroid</keyword>
  <keyword>Dry Eye</keyword>
  <keyword>Hyperemia</keyword>
  <keyword>Ocular Discomfort</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>
    <mesh_term>Eye Diseases</mesh_term>
    <mesh_term>Keratoconjunctivitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Loteprednol Etabonate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 26, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT02188160/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>KPI-121 0.25% Ophthalmic Suspension</title>
          <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease&#xD;
KPI-121: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
        <group group_id="P2">
          <title>Vehicle</title>
          <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease&#xD;
Placebo: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="73"/>
                <participants group_id="P2" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="72"/>
                <participants group_id="P2" count="76"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </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>Use of an excluded medication</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <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>KPI-121 0.25% Ophthalmic Suspension</title>
          <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease&#xD;
KPI-121: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
        <group group_id="B2">
          <title>Vehicle</title>
          <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease&#xD;
Placebo: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</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="73"/>
            <count group_id="B2" value="77"/>
            <count group_id="B3" value="150"/>
          </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="56.3" spread="17.17"/>
                    <measurement group_id="B2" value="54.9" spread="12.29"/>
                    <measurement group_id="B3" value="55.6" spread="14.83"/>
                  </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="53"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="114"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="119"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="117"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="73"/>
                    <measurement group_id="B2" value="77"/>
                    <measurement group_id="B3" value="150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Bulbar Conjunctival Hyperemia</title>
        <description>Comparison of mean bulbar conjunctival hyperemia in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.</description>
        <time_frame>Visit 6 (Day 29)</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease&#xD;
KPI-121: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease&#xD;
Placebo: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Bulbar Conjunctival Hyperemia</title>
          <description>Comparison of mean bulbar conjunctival hyperemia in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.</description>
          <population>ITT</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="73"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.22" spread="0.633"/>
                    <measurement group_id="O2" value="1.36" spread="0.626"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Ocular Discomfort</title>
        <description>Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.</description>
        <time_frame>Visit 6 (Day 29)</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease&#xD;
KPI-121: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease&#xD;
Placebo: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Ocular Discomfort</title>
          <description>Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.</description>
          <population>ITT</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="73"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.05" spread="23.892"/>
                    <measurement group_id="O2" value="60.47" spread="19.770"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Corneal Fluorescein Staining Scores</title>
        <description>Comparison of mean corneal fluorescein staining scores in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe. The total score is obtained by summing each of the 5 sections of the cornea. The NEI score will be from 0-15.</description>
        <time_frame>Visit 4 (Day 15) and Visit 6 (Day 29)</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease&#xD;
KPI-121: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease&#xD;
Placebo: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Corneal Fluorescein Staining Scores</title>
          <description>Comparison of mean corneal fluorescein staining scores in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe. The total score is obtained by summing each of the 5 sections of the cornea. The NEI score will be from 0-15.</description>
          <population>ITT</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="73"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Visit 4 (Day 15)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.15" spread="2.582"/>
                    <measurement group_id="O2" value="7.00" spread="2.920"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 6 (Day 29)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.64" spread="2.889"/>
                    <measurement group_id="O2" value="6.16" spread="3.445"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bulbar Conjunctival Hyperemia Scores</title>
        <description>Comparison of mean bulbar conjunctival hyperemia scores in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.</description>
        <time_frame>Visit 4 (Day 15)</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease&#xD;
KPI-121: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease&#xD;
Placebo: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Bulbar Conjunctival Hyperemia Scores</title>
          <description>Comparison of mean bulbar conjunctival hyperemia scores in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.</description>
          <population>ITT</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="73"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.36" spread="0.586"/>
                    <measurement group_id="O2" value="1.42" spread="0.676"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ocular Discomfort</title>
        <description>Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.</description>
        <time_frame>Visit 4 (Day 15)</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>KPI-121 0.25% Ophthalmic Suspension</title>
            <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease&#xD;
KPI-121: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease&#xD;
Placebo: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</description>
          </group>
        </group_list>
        <measure>
          <title>Ocular Discomfort</title>
          <description>Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.</description>
          <population>ITT</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="73"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.83" spread="20.745"/>
                    <measurement group_id="O2" value="63.63" spread="17.844"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected from Visit 2 (Day 1) through Visit 6 (Day 29).</time_frame>
      <desc>One Subject was randomized to KPI-121 0.25% but received vehicle. Therefore, 72 subjects are included in the KPI-121 0.25% group and 78 subjects are included in the vehicle group in the safety analyses.</desc>
      <group_list>
        <group group_id="E1">
          <title>KPI-121 0.25% Ophthalmic Suspension</title>
          <description>KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease&#xD;
KPI-121: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.</description>
        </group>
        <group group_id="E2">
          <title>Vehicle</title>
          <description>Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease&#xD;
Placebo: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 16.1.</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <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="72"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <description>One subject reported an SAE (cholelithiasis; KPI-121 0.25% group), which was considered unrelated to the study treatment; it was severe in intensity, led the subject to discontinue the study treatment, and ultimately resolved without sequelae.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA Version 16.1.</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="7" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Instillation site pain</sub_title>
                <counts group_id="E1" events="18" subjects_affected="7" subjects_at_risk="72"/>
                <counts group_id="E2" events="16" subjects_affected="8" subjects_at_risk="78"/>
              </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>The institution and Investigators participating in this trial shall have no right to publish or present the results of this study without the prior written consent of the sponsor.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>VP, Clinical Development</name_or_title>
      <organization>Kala Pharmaceuticals, Inc.</organization>
      <phone>781-996-5252</phone>
      <email>results002@kalarx.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/NCT02188160
org study id: KPI-121-C-002
nct id: NCT02188160
lead sponsor: 
has dmc: No
The primary purpose of this study is to determine the efficacy and safety of KPI-121 0.25%
      ophthalmic suspension compared to vehicle (placebo) in subjects who have a documented
      clinical diagnosis of dry eye disease. The product will be studied over 28 days, with 1-2
      drops instilled in each eye four times daily (QID).
This is a Phase II, multi-center, double-masked, randomized, vehicle-controlled,
      parallel-group study designed to evaluate the safety and efficacy of KPI-121 0.25% ophthalmic
      suspension versus vehicle in subjects with dry eye disease.

      Approximately 400 subjects will be screened and up to 150 subjects will be randomized at up
      to 12 centers located in the United States. Subjects will be randomized to 1 of 2 study arms
      in an approximate 1:1 ratio. The study arms are: 1) KPI-121 0.25% ophthalmic suspension
      administered 1-2 drops in each eye QID for up to 28 days or 2) vehicle administered as 1-2
      drops in each eye QID for up to 28 days.

      This study will include up to 6 clinic visits over 6 weeks. At Visit 1 Screening (14 ± 1 days
      prior to Day 1), subjects who meet screening inclusion/exclusion criteria will begin a 2-week
      run-in period during which they will be treated with 1-2 drops of single-masked vehicle in
      each eye QID for 14 ± 1 days.

      At Visit 2, Randomization (Day 1), subjects who continue to meet inclusion/exclusion criteria
      will be eligible for randomization to 1 of the 2 arms of the study (i.e., KPI-121 0.25%
      ophthalmic suspension or vehicle). Following randomization, subjects will be instructed to
      return to the clinic to have a complete study evaluation at Study Visits 4 and 6 (Days 15 ± 1
      day and 29 ± 1 day, respectively). Subjects will further be instructed to return to the
      clinic for diary collection and in-clinic symptom assessment only at Visits 3 and 5 (Days 8 ±
      1 day and 22 ± 1 day, respectively). The last dose of investigational product and the final
      study visit will occur upon completion of 28 ± 1 days of exposure to investigational product.
      Subjects will be released from the study at the end of Visit 6 (Day 29 ± 1 day).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Bulbar Conjunctival Hyperemia
time frame: Visit 6 (Day 29)
description: Comparison of mean bulbar conjunctival hyperemia in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.
measure: Ocular Discomfort
time frame: Visit 6 (Day 29)
description: Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.
measure: Corneal Fluorescein Staining Scores
time frame: Visit 4 (Day 15) and Visit 6 (Day 29)
description: Comparison of mean corneal fluorescein staining scores in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe. The total score is obtained by summing each of the 5 sections of the cornea. The NEI score will be from 0-15.
measure: Bulbar Conjunctival Hyperemia Scores
time frame: Visit 4 (Day 15)
description: Comparison of mean bulbar conjunctival hyperemia scores in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe.
measure: Ocular Discomfort
time frame: Visit 4 (Day 15)
description: Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse.
arm group label: KPI-121 0.25% Ophthalmic Suspension
arm group type: Active Comparator
description: KPI-121 0.25% ophthalmic suspension dosed QID for 28 days in subjects with dry eye disease
arm group label: Vehicle
arm group type: Placebo Comparator
description: Vehicle (placebo) dosed QID for 28 days in subjects with dry eye disease
intervention type: Drug
intervention name: KPI-121
description: KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
arm group label: KPI-121 0.25% Ophthalmic Suspension
other name: KPI-121 0.25% Ophthalmic Suspension
other name: Loteprednol etabonate
intervention type: Drug
intervention name: Placebo
description: Subjects randomized to placebo control arms will receive the same bottles containing all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.
arm group label: Vehicle
other name: Vehicle of KPI-121 0.25% Ophthalmic Suspension
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gregg Berdy, MD
role: Principal Investigator
affiliation: Ophthalmology Associates
last name: David Evans, OD
role: Principal Investigator
affiliation: Total Eye Care, PA
last name: Kathy Kelley, OD
role: Principal Investigator
affiliation: Price Vision Group
last name: Joseph Martel, MD
role: Principal Investigator
affiliation: Martel Eye Medical Group
last name: Mark Milner, MD
role: Principal Investigator
affiliation: Eye Center of Southern CT, P.C.
last name: Steven Rauchman, MD
role: Principal Investigator
affiliation: North Valley Eye Medical Group
last name: Kenneth Sall, MD
role: Principal Investigator
affiliation: Sall Research Medical Center
last name: Jeffrey Whitsett, MD
role: Principal Investigator
affiliation: Whitsett Vision Group
last name: Marc Abrams, MD
role: Principal Investigator
affiliation: Abrams Eye Center
last name: Michael Korenfeld, MD
role: Principal Investigator
affiliation: Ecomprehensive Eye Care, Ltd / Vision Research Institute LLC
last name: Jodi Luchs, MD
role: Principal Investigator
affiliation: South Shore Eye Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Eye Diseases
mesh term: Keratoconjunctivitis
mesh term: Loteprednol Etabonate
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 