<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/NCT02975557</url>
  </required_header>
  <id_info>
    <org_study_id>2015-0278</org_study_id>
    <nct_id>NCT02975557</nct_id>
  </id_info>
  <brief_title>Brimonidine Eye Drops for Treatment of Ocular Graft-vs-Host Disease (oGVHD)</brief_title>
  <official_title>A Phase I/II Randomized, Placebo-Controlled, Double-Blind, Single-Center, Tolerability And Preliminary Efficacy Study Of Use of Brimonidine Eye Drops for Treatment of Ocular Graft-vs-Host Disease (oGVHD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sandeep Jain, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ocugen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Illinois at Chicago</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to establish whether patients with dry eye disease (DED) are&#xD;
      able to tolerate receiving Brimonidine: 0.15% eye drops two times a day for twelve weeks&#xD;
      (primary tolerability objective) and to investigate the preliminary efficacy of Brimonidine&#xD;
      0.15% topical eye drop solution in treating Meibomian Gland Dysfunction (MGD) (primary&#xD;
      efficacy objective).&#xD;
&#xD;
      Meibomian Gland dysfunction can happen with numerous conditions such as Rosacea, Sjögren's&#xD;
      syndrome, and oGVHD. In order to limit the influence of differing etiologies on the outcome&#xD;
      of this trial, the investigator has limited the screening to MGD that accompanies oGVHD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow accrual of subjects. May take longer than expected to complete the trial.&#xD;
  </why_stopped>
  <start_date type="Actual">May 2016</start_date>
  <completion_date type="Actual">April 13, 2017</completion_date>
  <primary_completion_date type="Actual">April 13, 2017</primary_completion_date>
  <phase>Phase 1/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>Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Subjects assessed their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end and marks at an equal distance starting from 0 mm and leading up to 100 mm (0 10 20 30 40 50 60 70 80 90 100). The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), week 3, week 6, week 9 and week 12. Subjects will place a single slash mark across the horizontal line between the end labeled &quot;completely intolerable&quot; (0 mm) and &quot;easily tolerable&quot; (100mm).</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Dry Eye</condition>
  <condition>Ocular Graft vs Host Disease</condition>
  <condition>Meibomian Gland Dysfunction</condition>
  <arm_group>
    <arm_group_label>Brimonidine 0.15%</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Brimonidine 0.15% eye drops 2 times a day for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Brimonidine 0.075%</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brimonidine 0.15%</intervention_name>
    <description>Brimonidine 0.15% eye drops 2 times a day for 12 weeks</description>
    <arm_group_label>Brimonidine 0.15%</arm_group_label>
    <other_name>Alphagan P</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brimonidine 0.075%</intervention_name>
    <description>Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.</description>
    <arm_group_label>Brimonidine 0.075%</arm_group_label>
    <other_name>Alphagan P</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Refresh plus Artificial Tear</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged 18 years or older.&#xD;
&#xD;
          2. Capable of giving informed consent and does provide informed consent.&#xD;
&#xD;
          3. Diagnosis of Meibomian Gland Disease&#xD;
&#xD;
          4. Women must be post-menopausal ≥ 1 year, or surgically sterilized. If not, a negative&#xD;
             urine pregnancy test is required within 7 days of the participant receiving first dose&#xD;
             of study drug along with definite evidence of contraceptive use during the duration of&#xD;
             the study. Women of reproductive age should use a method of birth control that is&#xD;
             acceptable to the participant and the study doctor. This may include oral&#xD;
             contraceptive pills, birth control implants, barrier methods or abstinence. If a&#xD;
             participant suspects pregnancy after being enrolled, another pregnancy test will be&#xD;
             administered. If the test is positive, the participant will be discontinued from the&#xD;
             study immediately.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergic to Brimonidine or any similar products, or excipients of Brimonidine&#xD;
&#xD;
          2. Currently receiving any Brimonidine preparation as a part of glaucoma management&#xD;
&#xD;
          3. Receiving or have received within 30 days any experimental systemic medication.&#xD;
&#xD;
          4. Active ocular infection or ocular allergies.&#xD;
&#xD;
          5. Any history of eyelid surgery or ocular surgery within the past 3 months.&#xD;
&#xD;
          6. Corneal epithelial defect larger than 1 mm2 in either eye.&#xD;
&#xD;
          7. Have active drug/alcohol dependence or abuse history.&#xD;
&#xD;
          8. Vulnerable populations, such as neonates, pregnant women, children, prisoners,&#xD;
             institutionalized individuals, or others who may be considered vulnerable populations.&#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>Sandeep Jain, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Illinois at Chicago</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Illinois Eye and Ear Infirmary, University of Illinois</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Translational Clinic of Corneal Neurobiology Laboratory, Illinois Eye and Ear Infirmary, University of Illinois</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://chicago.medicine.uic.edu/directory/name/sandeep-jain-md-jain/</url>
    <description>Principal Investigator description</description>
  </link>
  <link>
    <url>http://eyecare.uic.edu/clinics/DryEyeandOcularGVHDclinic.shtml</url>
    <description>Dry Eye and ocular GVHD Clinic at University of Illinois at Chicago</description>
  </link>
  <link>
    <url>http://cornealneurobiology.uic.edu/</url>
    <description>Corneal Neurobiology Laboratory (National Eye Institute funded)</description>
  </link>
  <reference>
    <citation>Tibrewal S, Sarkar J, Jassim SH, Gandhi S, Sonawane S, Chaudhary S, Byun YS, Ivanir Y, Hallak J, Horner JH, Newcomb M, Jain S. Tear fluid extracellular DNA: diagnostic and therapeutic implications in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Dec 11;54(13):8051-61. doi: 10.1167/iovs.13-12844.</citation>
    <PMID>24255046</PMID>
  </reference>
  <reference>
    <citation>Sonawane S, Khanolkar V, Namavari A, Chaudhary S, Gandhi S, Tibrewal S, Jassim SH, Shaheen B, Hallak J, Horner JH, Newcomb M, Sarkar J, Jain S. Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm for inflammation in dry eye disease. Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8253-63. doi: 10.1167/iovs.12-10430.</citation>
    <PMID>23169882</PMID>
  </reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <results_first_submitted>September 27, 2019</results_first_submitted>
  <results_first_submitted_qc>November 7, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 8, 2019</results_first_posted>
  <last_update_submitted>November 7, 2019</last_update_submitted>
  <last_update_submitted_qc>November 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Illinois at Chicago</investigator_affiliation>
    <investigator_full_name>Sandeep Jain, MD</investigator_full_name>
    <investigator_title>Professor of Ophthalmology</investigator_title>
  </responsible_party>
  <keyword>Brimonidine</keyword>
  <keyword>Dry Eye</keyword>
  <keyword>oGVHD</keyword>
  <keyword>MGD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Meibomian Gland Dysfunction</mesh_term>
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brimonidine Tartrate</mesh_term>
    <mesh_term>Lubricant Eye Drops</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>February 9, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02975557/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02975557/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited from the clinical practice of the investigator at the time of their routine eye examination visit. The clinical practice is located in the Illinois Eye and Ear Infirmary (EEI), the University of Illinois at Chicago (UIC). The first participant was enrolled in May 2016, and the last participant was enrolled in February 2017.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Brimonidine 0.15%</title>
          <description>Brimonidine 0.15% eye drops 2 times a day for 12 weeks&#xD;
Brimonidine 0.15%: Brimonidine 0.15% eye drops 2 times a day for 12 weeks</description>
        </group>
        <group group_id="P2">
          <title>Brimonidine 0.075%</title>
          <description>Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.&#xD;
Brimonidine 0.075%: Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.&#xD;
Placebo: Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 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="4"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Brimonidine 0.15%</title>
          <description>Brimonidine 0.15% eye drops 2 times a day for 12 weeks&#xD;
Brimonidine 0.15%: Brimonidine 0.15% eye drops 2 times a day for 12 weeks</description>
        </group>
        <group group_id="B2">
          <title>Brimonidine 0.075%</title>
          <description>Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.&#xD;
Brimonidine 0.075%: Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.&#xD;
Placebo: Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 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="4"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="10"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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 group_id="B4" value="0"/>
                  </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="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ocular Surface Disease Index (OSDI)</title>
          <description>Ocular Surface Disease Index (OSDI), 12-item questionnaire, assesses symptom of ocular irritation in dry eye disease (DED) and how it affects functioning related to vision in past week. It has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on 0 to 4 scale with 0 being &quot;none of the time&quot; and 4 being &quot;all of the time.&quot; OSDI score range from 0-100 with score 0-12 being normal, 13-22 being mild DED, 23-32 being moderate DED, and &gt;33 being severe DED. OSDI=[(sum of scores for questions answered)×100]/[(total questions answered)×4]</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48.4" spread="8.32"/>
                    <measurement group_id="B2" value="61.36" spread="22.42"/>
                    <measurement group_id="B3" value="56.03" spread="22.99"/>
                    <measurement group_id="B4" value="55.72" spread="20.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Schirmer I Test</title>
          <description>The Schirmer's I tests consists of a thin strip of filter paper placed in lower conjunctival fornix (between the lower eyelid and ocular surface) for 5 minutes. The length of wetting of the strip is used as a measure of tear production by the eye. A normal level of production is considered to be over 10 millimeters (mm) of tears on the paper. Anything under 10 mm is considered to be an abnormally low level of tear production. A measurement of less than 5 mm is considered severe dry eye.</description>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.75" spread="8.42"/>
                    <measurement group_id="B2" value="2" spread="4.47"/>
                    <measurement group_id="B3" value="0.33" spread="0.74"/>
                    <measurement group_id="B4" value="1.4" spread="2.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks.</title>
        <description>Subjects assessed their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end and marks at an equal distance starting from 0 mm and leading up to 100 mm (0 10 20 30 40 50 60 70 80 90 100). The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), week 3, week 6, week 9 and week 12. Subjects will place a single slash mark across the horizontal line between the end labeled &quot;completely intolerable&quot; (0 mm) and &quot;easily tolerable&quot; (100mm).</description>
        <time_frame>12 weeks</time_frame>
        <population>The sponsor terminated the research early citing slow accrual of subjects and ceased sponsorship. At this point, the available valid sample size was 11 subjects at 12 weeks for assessing the tolerability at 12 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Brimonidine 0.15%</title>
            <description>Brimonidine 0.15% eye drops 2 times a day for 12 weeks&#xD;
Brimonidine 0.15%: Brimonidine 0.15% eye drops 2 times a day for 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Brimonidine 0.075%</title>
            <description>Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.&#xD;
Brimonidine 0.075%: Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.&#xD;
Placebo: Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks.</title>
          <description>Subjects assessed their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end and marks at an equal distance starting from 0 mm and leading up to 100 mm (0 10 20 30 40 50 60 70 80 90 100). The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), week 3, week 6, week 9 and week 12. Subjects will place a single slash mark across the horizontal line between the end labeled &quot;completely intolerable&quot; (0 mm) and &quot;easily tolerable&quot; (100mm).</description>
          <population>The sponsor terminated the research early citing slow accrual of subjects and ceased sponsorship. At this point, the available valid sample size was 11 subjects at 12 weeks for assessing the tolerability at 12 weeks.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tolerability (100%)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tolerability (95%)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tolerability (90%)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </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>O3</group_id>
            </group_id_list>
            <groups_desc>We evaluated if the categorical type of tolerability measure is different between control (Artificial Tears) and intervention (Brimonidine, including both 0.15% high and 0.075% low doses groups).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>1</p_value>
            <method>Fisher Exact</method>
            <method_desc>The type I error was adjusted by using the alpha spending function approach with O'Brien-Fleming type boundaries.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Brimonidine 0.15%</title>
          <description>Brimonidine 0.15% eye drops 2 times a day for 12 weeks&#xD;
Brimonidine 0.15%: Brimonidine 0.15% eye drops 2 times a day for 12 weeks</description>
        </group>
        <group group_id="E2">
          <title>Brimonidine 0.075%</title>
          <description>Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.&#xD;
Brimonidine 0.075%: Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.&#xD;
Placebo: Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
              </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>
    <limitations_and_caveats>Given the inadequate power to detect efficacy (due to 40% enrollment), we did not perform an analysis to determine whether the drug had any beneficial effect. Due to slow accrual of subjects in this clinical trial sponsor ceased sponsorship.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Sandeep Jain</name_or_title>
      <organization>Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL</organization>
      <phone>312-996-4476</phone>
      <email>jains@uic.edu</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/NCT02975557
org study id: 2015-0278
nct id: NCT02975557
lead sponsor: 
collaborator: 
has dmc: No
The objective of this study is to establish whether patients with dry eye disease (DED) are
      able to tolerate receiving Brimonidine: 0.15% eye drops two times a day for twelve weeks
      (primary tolerability objective) and to investigate the preliminary efficacy of Brimonidine
      0.15% topical eye drop solution in treating Meibomian Gland Dysfunction (MGD) (primary
      efficacy objective).

      Meibomian Gland dysfunction can happen with numerous conditions such as Rosacea, Sjögren's
      syndrome, and oGVHD. In order to limit the influence of differing etiologies on the outcome
      of this trial, the investigator has limited the screening to MGD that accompanies oGVHD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Primary Tolerability End Point: The Test Substance Tolerance (Visual Analog Scale) at 12 Weeks.
time frame: 12 weeks
description: Subjects assessed their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100 mm horizontal line with verbal descriptors at either end and marks at an equal distance starting from 0 mm and leading up to 100 mm (0 10 20 30 40 50 60 70 80 90 100). The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), week 3, week 6, week 9 and week 12. Subjects will place a single slash mark across the horizontal line between the end labeled "completely intolerable" (0 mm) and "easily tolerable" (100mm).
arm group label: Brimonidine 0.15%
arm group type: Active Comparator
description: Brimonidine 0.15% eye drops 2 times a day for 12 weeks
arm group label: Brimonidine 0.075%
arm group type: Active Comparator
description: Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.
intervention type: Drug
intervention name: Brimonidine 0.15%
description: Brimonidine 0.15% eye drops 2 times a day for 12 weeks
arm group label: Brimonidine 0.15%
other name: Alphagan P
intervention type: Drug
intervention name: Brimonidine 0.075%
description: Brimonidine 0.075% (1:1 dilution will be performed using 0.15% Alphagan-P solution with Refresh Plus Artificial Tears solution) eye drops 2 times a day for 12 weeks.
arm group label: Brimonidine 0.075%
other name: Alphagan P
intervention type: Drug
intervention name: Placebo
description: Placebo (Refresh plus Artificial Tear) dispensed in Brimonidine bottles 2 times a day for 12 weeks.
arm group label: Placebo
other name: Refresh plus Artificial Tear
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sandeep Jain, MD
role: Principal Investigator
affiliation: University of Illinois at Chicago
facility: 
facility: 
country: United States
url: http://chicago.medicine.uic.edu/directory/name/sandeep-jain-md-jain/
description: Principal Investigator description
url: http://eyecare.uic.edu/clinics/DryEyeandOcularGVHDclinic.shtml
description: Dry Eye and ocular GVHD Clinic at University of Illinois at Chicago
url: http://cornealneurobiology.uic.edu/
description: Corneal Neurobiology Laboratory (National Eye Institute funded)
citation: Tibrewal S, Sarkar J, Jassim SH, Gandhi S, Sonawane S, Chaudhary S, Byun YS, Ivanir Y, Hallak J, Horner JH, Newcomb M, Jain S. Tear fluid extracellular DNA: diagnostic and therapeutic implications in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Dec 11;54(13):8051-61. doi: 10.1167/iovs.13-12844.
PMID: 24255046
citation: Sonawane S, Khanolkar V, Namavari A, Chaudhary S, Gandhi S, Tibrewal S, Jassim SH, Shaheen B, Hallak J, Horner JH, Newcomb M, Sarkar J, Jain S. Ocular surface extracellular DNA and nuclease activity imbalance: a new paradigm for inflammation in dry eye disease. Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8253-63. doi: 10.1167/iovs.12-10430.
PMID: 23169882
responsible party type: Sponsor-Investigator
investigator affiliation: University of Illinois at Chicago
investigator full name: Sandeep Jain, MD
investigator title: Professor of Ophthalmology
mesh term: Dry Eye Syndromes
mesh term: Meibomian Gland Dysfunction
mesh term: Graft vs Host Disease
mesh term: Brimonidine Tartrate
mesh term: Lubricant Eye Drops
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Given the inadequate power to detect efficacy (due to 40% enrollment), we did not perform an analysis to determine whether the drug had any beneficial effect. Due to slow accrual of subjects in this clinical trial sponsor ceased sponsorship.
point of contact: 