<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/NCT04498182</url>
  </required_header>
  <id_info>
    <org_study_id>AR15512-CS201</org_study_id>
    <nct_id>NCT04498182</nct_id>
  </id_info>
  <brief_title>A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease</brief_title>
  <acronym>COMET-1</acronym>
  <official_title>A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease (COMET-1)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aerie Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aerie Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2b, multicenter, vehicle-controlled, double-masked, randomized study. All&#xD;
      subjects enrolled will have dry eye disease. The study consists of Screening and Baseline&#xD;
      visits to determine eligibility followed by efficacy assessments at Day 14 (Visit 3), 28&#xD;
      (Visit 4) and 84 (Visit 5 / Study Exit). Safety will be assessed at all study visits. All&#xD;
      subjects will be exposed to the Controlled Adverse Environment (CAE®) at the Screening,&#xD;
      Baseline, Day 28 and Day 84 visits. Only subjects who qualify based on inclusion/exclusion&#xD;
      criteria, will be enrolled in the study and randomized at a 1:1:1 ratio within each site, to&#xD;
      receive AR-15512 0.0014%, AR-15512 0.003% or AR-15512 vehicle to be administered as 1 drop in&#xD;
      each eye twice daily for 84 days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 10, 2020</start_date>
  <completion_date type="Actual">July 20, 2021</completion_date>
  <primary_completion_date type="Actual">July 20, 2021</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>
    <intervention_model_description>Subjects will be randomized at a 1:1:1 ratio within each site to receive AR-15512 0.0014%, AR-15512 0.003% or AR 15512 vehicle</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>During the randomized treatment period, the investigator and site staff performing eligibility / efficacy and safety assessments and the subjects will be masked. Subjects will be informed that they all will receive vehicle at some point in the study, but the exact timing will not be specified.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Ocular Discomfort Score (ODS) on a Visual Analogue Scale (VAS) from 0 (no ocular discomfort) to 100 (maximum ocular discomfort) millimeters</measure>
    <time_frame>28 days</time_frame>
    <description>Improvement from baseline in pre-Controlled Adverse Environment (CAE) ODS-VAS where a lower score is indicative of a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Anesthetized Schirmer Test from 0 to 35 millimeters</measure>
    <time_frame>28 days</time_frame>
    <description>Improvement from baseline in pre-Controlled Adverse Environment (CAE) anesthetized Schirmer score where a higher score is indicative of a better outcome.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">369</enrollment>
  <condition>Dry Eye Disease</condition>
  <arm_group>
    <arm_group_label>AR15512 Ophthalmic Solution (0.0014%)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low Dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AR15512 Ophthalmic Solution (0.003%)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High Dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vehicle</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>AR15512 Ophthalmic Solution Vehicle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AR15512</intervention_name>
    <description>Administered via topical ocular instillation, one drop per eye, twice daily for 84 days. Both eyes will be treated.</description>
    <arm_group_label>AR15512 Ophthalmic Solution (0.0014%)</arm_group_label>
    <arm_group_label>AR15512 Ophthalmic Solution (0.003%)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vehicle</intervention_name>
    <description>Administered via topical ocular instillation, one drop per eye, twice daily for 84 days. Both eyes will be treated.</description>
    <arm_group_label>Vehicle</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, 30 years of age or older at the Screening visit&#xD;
&#xD;
          -  Signs of DED at the Screening and Baseline visits assessed by corneal staining and&#xD;
             Schirmer test&#xD;
&#xD;
          -  Symptoms of DED at both Screening and Baseline visits assessed by SANDE questionnaire&#xD;
             and ODS-VAS&#xD;
&#xD;
          -  BCVA 20/200 (+0.70 LogMAR) or better in both eyes at both the Screening and Baseline&#xD;
             visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or presence of any ocular disorder or condition (other than DED) in either eye&#xD;
             that would, in the opinion of the investigator, likely interfere with the&#xD;
             interpretation of the study results or subject safety.&#xD;
&#xD;
          -  Current evidence of other significant ophthalmic disease requiring topical medication&#xD;
             (e.g. glaucoma, ocular hypertension), which may interfere with vision (e.g., cataract,&#xD;
             macular degeneration) or other disease which the investigator believes may interfere&#xD;
             with study findings or interpretation.&#xD;
&#xD;
          -  History of ocular surgery within 1 year prior to the Screening visit.&#xD;
&#xD;
          -  Corneal transplant in either or both eyes.&#xD;
&#xD;
          -  Use of contact lenses in either eye within 7 days prior to the Screening visit or&#xD;
             planned use during the study.&#xD;
&#xD;
          -  Punctal or intracanalicular plug present in either eyelid within 1 year prior to the&#xD;
             Screening visit or anticipated plug insertion or occlusion at any time during the&#xD;
             study.&#xD;
&#xD;
          -  Use of artificial tears within 2 hours prior to the Screening visit or anticipated use&#xD;
             during the study.&#xD;
&#xD;
          -  Regular use of any topical ocular medications (including use of ocular cyclosporine or&#xD;
             other prescription ophthalmic solution for DED, topical ocular corticosteroid- or&#xD;
             non-steroidal-anti-inflammatory agents, glaucoma medications or other&#xD;
             over-the-counter, herbal, prescription, any topical antibiotics, topical&#xD;
             antihistamines, mast stabilizers, or nutritional supplements with the exception of&#xD;
             artificial tears), within 30 days prior to the Screening visit or anticipated use&#xD;
             during the study. Note: Occasional (as needed) &gt;24 hours prior to the Screening Visit&#xD;
             may be permitted&#xD;
&#xD;
          -  Use of medications associated with the treatment of severe DED and/or Meibomian gland&#xD;
             disease such as oral pilocarpine, oral cevimeline, oral macrolides, oral&#xD;
             tetracyclines, oral tetracycline derivatives, and oral retinoids within 90 days prior&#xD;
             to the Baseline visit or anticipated use during the study&#xD;
&#xD;
          -  Use of systemic corticosteroids started &lt; 90 days prior to the Baseline Visit or a&#xD;
             change in dosage is anticipated during the study. Note: Non-ocular topically applied&#xD;
             corticosteroids (including nasal sprays and inhalers) will be permitted during the&#xD;
             study and the dose is not required to be stable.&#xD;
&#xD;
          -  Use of TrueTear® within 45 days of the Screening visit or anticipated use during the&#xD;
             study.&#xD;
&#xD;
          -  Use of lid heating therapy or Meibomian gland probing/therapeutic expression within 1&#xD;
             year prior to the Screening visit or anticipated during the study.&#xD;
&#xD;
          -  Use of systemic immunomodulators started &lt; 90 days prior to the Baseline visit or a&#xD;
             change in dosage is anticipated during the study.&#xD;
&#xD;
          -  Any systemic medication known to cause ocular drying (ex/antihistamines,&#xD;
             anti-depressants, beta-blockers) started &lt; 14 days prior to the Screening visit or a&#xD;
             change in dosage is anticipated during the study. Note: Occasional (as needed) use of&#xD;
             medications such as systemic antihistamines will be permitted&#xD;
&#xD;
          -  Diagnosis of recurrent, ongoing, or active ocular infection including, but not limited&#xD;
             to herpes simplex or zoster, vaccinia, varicella, tuberculosis of the eye,&#xD;
             acanthamoeba, or fungal disease.&#xD;
&#xD;
          -  History or presence of significant systemic disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michelle Senchyna, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Aerie Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Carmel</city>
        <state>Indiana</state>
        <zip>46290</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Andover</city>
        <state>Massachusetts</state>
        <zip>01810</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Raynham</city>
        <state>Massachusetts</state>
        <zip>02767</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Hamel</city>
        <state>Minnesota</state>
        <zip>55340</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Shelby</city>
        <state>North Carolina</state>
        <zip>28150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Smyrna</city>
        <state>Tennessee</state>
        <zip>37167</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Layton</city>
        <state>Utah</state>
        <zip>84041</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Investigator</name>
      <address>
        <city>Lynchburg</city>
        <state>Virginia</state>
        <zip>24502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <disposition_first_submitted>July 19, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>July 19, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">July 21, 2022</disposition_first_posted>
  <last_update_submitted>July 19, 2022</last_update_submitted>
  <last_update_submitted_qc>July 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
    <mesh_term>Eye Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04498182
org study id: AR15512-CS201
nct id: NCT04498182
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 2b, multicenter, vehicle-controlled, double-masked, randomized study. All
      subjects enrolled will have dry eye disease. The study consists of Screening and Baseline
      visits to determine eligibility followed by efficacy assessments at Day 14 (Visit 3), 28
      (Visit 4) and 84 (Visit 5 / Study Exit). Safety will be assessed at all study visits. All
      subjects will be exposed to the Controlled Adverse Environment (CAE®) at the Screening,
      Baseline, Day 28 and Day 84 visits. Only subjects who qualify based on inclusion/exclusion
      criteria, will be enrolled in the study and randomized at a 1:1:1 ratio within each site, to
      receive AR-15512 0.0014%, AR-15512 0.003% or AR-15512 vehicle to be administered as 1 drop in
      each eye twice daily for 84 days.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects will be randomized at a 1:1:1 ratio within each site to receive AR-15512 0.0014%, AR-15512 0.003% or AR 15512 vehicle
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: During the randomized treatment period, the investigator and site staff performing eligibility / efficacy and safety assessments and the subjects will be masked. Subjects will be informed that they all will receive vehicle at some point in the study, but the exact timing will not be specified.
measure: Ocular Discomfort Score (ODS) on a Visual Analogue Scale (VAS) from 0 (no ocular discomfort) to 100 (maximum ocular discomfort) millimeters
time frame: 28 days
description: Improvement from baseline in pre-Controlled Adverse Environment (CAE) ODS-VAS where a lower score is indicative of a better outcome.
measure: Anesthetized Schirmer Test from 0 to 35 millimeters
time frame: 28 days
description: Improvement from baseline in pre-Controlled Adverse Environment (CAE) anesthetized Schirmer score where a higher score is indicative of a better outcome.
arm group label: AR15512 Ophthalmic Solution (0.0014%)
arm group type: Experimental
description: Low Dose
arm group label: AR15512 Ophthalmic Solution (0.003%)
arm group type: Experimental
description: High Dose
arm group label: Vehicle
arm group type: Placebo Comparator
description: AR15512 Ophthalmic Solution Vehicle
intervention type: Drug
intervention name: AR15512
description: Administered via topical ocular instillation, one drop per eye, twice daily for 84 days. Both eyes will be treated.
arm group label: AR15512 Ophthalmic Solution (0.0014%)
arm group label: AR15512 Ophthalmic Solution (0.003%)
intervention type: Drug
intervention name: Vehicle
description: Administered via topical ocular instillation, one drop per eye, twice daily for 84 days. Both eyes will be treated.
arm group label: Vehicle
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Michelle Senchyna, PhD
role: Study Director
affiliation: Aerie Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
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
sharing ipd: No