<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/NCT02207621</url>
  </required_header>
  <id_info>
    <org_study_id>AR-13324-CS302</org_study_id>
    <nct_id>NCT02207621</nct_id>
  </id_info>
  <brief_title>Evaluation of Netarsudil (AR-13324) Ophthalmic Solution in Patients With Glaucoma and Ocular Hypertension</brief_title>
  <official_title>A Double-masked, Randomized, Multi-center, Active-controlled, Parallel, 12-month Study Assessing the Safety and Ocular Hypotensive Efficacy of AR-13324 Ophthalmic Solution, 0.02% q.d. and b.i.d. Compared to Timolol Maleate Ophthalmic Solution, 0.5% b.i.d. in Patients With Elevated Intraocular Pressure</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluation of the ocular hypotensive efficacy and safety of Netarsudil (AR-13324) Ophthalmic&#xD;
      Solution compared to Timolol Maleate Ophthalmic Solution&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intraocular Pressure (IOP)</measure>
    <time_frame>3 months</time_frame>
    <description>The primary efficacy outcome is mean intraocular pressure (IOP)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Extent of Exposure</measure>
    <time_frame>12 Months</time_frame>
    <description>Exposure to study medication in days for all treatment groups</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">756</enrollment>
  <condition>Ocular Hypertension</condition>
  <condition>Open-angle Glaucoma</condition>
  <arm_group>
    <arm_group_label>AR-13324 Ophthalmic Solution 0.02% &amp; placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 drop AR-13324 in the evening (PM) &amp; 1 drop placebo in the morning (AM) in both eyes (OU)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Timolol maleate Ophthalmic Solution 0.5% BID</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AR-13324 Ophthalmic Solution 0.02% BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 drop AR-13324 twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AR-13324 Ophthalmic Solution 0.02%</intervention_name>
    <description>1 drop once daily (QD), PM, OU</description>
    <arm_group_label>AR-13324 Ophthalmic Solution 0.02% &amp; placebo</arm_group_label>
    <other_name>Netarsudil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Timolol maleate Ophthalmic Solution 0.5% BID</intervention_name>
    <description>1 drop BID, AM/PM, OU</description>
    <arm_group_label>Timolol maleate Ophthalmic Solution 0.5% BID</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>1 drop QD, AM, OU</description>
    <arm_group_label>AR-13324 Ophthalmic Solution 0.02% &amp; placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AR-13324 Ophthalmic Solution 0.02% BID</intervention_name>
    <description>1 drop BID, AM/PM, OU</description>
    <arm_group_label>AR-13324 Ophthalmic Solution 0.02% BID</arm_group_label>
    <other_name>Netarsudil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Subject inclusion criteria&#xD;
&#xD;
          1. 0-2 years of age and 18 years or greater&#xD;
&#xD;
          2. Diagnosis of open angle glaucoma or ocular hypertension&#xD;
&#xD;
          3. Unmedicated (post-washout) intraocular pressure (IOP) &gt;20 mm Hg and &lt; 27 mm Hg in the&#xD;
             study eye at 2 qualification visits&#xD;
&#xD;
          4. Corrected visual acuity in each eye equivalent to 20/200&#xD;
&#xD;
          5. Able and willing to give signed informed consent (parent or guardian consent for&#xD;
             pediatric patient) and follow study instructions&#xD;
&#xD;
        Subject exclusion criteria&#xD;
&#xD;
        Ophthalmic:&#xD;
&#xD;
          1. Glaucoma: pseudoexfoliation or pigment dispersion component, history of angle closure,&#xD;
             or narrow angles. Note: Previous laser peripheral iridotomy is NOT acceptable.&#xD;
&#xD;
          2. Intraocular pressure ≥27 mm Hg (unmedicated) in both eyes or use of more than two&#xD;
             ocular hypotensive medications within 30 days of screening. Note: fixed dose&#xD;
             combinations count as two medications.&#xD;
&#xD;
          3. Known hypersensitivity to any component of the formulations to be used (benzalkonium&#xD;
             chloride, etc.), to topical anesthetics or beta-adrenoceptor antagonists.&#xD;
&#xD;
          4. Previous glaucoma intraocular surgery or glaucoma laser procedures in either eye&#xD;
&#xD;
          5. Refractive surgery in either eye.&#xD;
&#xD;
          6. Ocular trauma in either eye within the six months prior to screening, or ocular&#xD;
             surgery or non-refractive laser treatment within the three months prior to screening.&#xD;
&#xD;
          7. Recent or current evidence of ocular infection or inflammation in either eye. Current&#xD;
             evidence of clinically significant blepharitis, conjunctivitis, or a history of herpes&#xD;
             simplex or zoster keratitis at screening in either eye.&#xD;
&#xD;
          8. Ocular medication in either eye of any kind within 30 days of screening.&#xD;
&#xD;
          9. Clinically significant ocular disease in either eye (e.g., corneal edema, uveitis,&#xD;
             severe keratoconjunctivitis sicca) which might interfere with the study, including&#xD;
             glaucomatous damage so severe that washout of ocular hypotensive medications for one&#xD;
             month is not judged safe.&#xD;
&#xD;
         10. Central corneal thickness in either eye greater than 600 µm at screening.&#xD;
&#xD;
         11. Any abnormality in either eye preventing reliable applanation tonometry of either eye.&#xD;
&#xD;
             Systemic:&#xD;
&#xD;
         12. Clinically relevant abnormalities (as determined by the investigator) in laboratory&#xD;
             tests at screening which may impact the study.&#xD;
&#xD;
         13. Known hypersensitivity or contraindication to beta-adrenoceptor antagonists (e.g.,&#xD;
             chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood&#xD;
             pressure or heart rate; second or third degree heart block or congestive heart&#xD;
             failure; severe diabetes).&#xD;
&#xD;
         14. Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia&#xD;
             gravis, hepatic, renal, endocrine or cardiovascular disorders) which might interfere&#xD;
             with the study.&#xD;
&#xD;
         15. Participation in any investigational study within 30 days prior to screening.&#xD;
&#xD;
         16. Changes of systemic medication that could have an effect on intraocular pressure&#xD;
             within 30 days prior to screening, or anticipated during the study.&#xD;
&#xD;
         17. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or&#xD;
             not using a medically acceptable form of birth control. An adult woman is considered&#xD;
             to be of childbearing potential unless she is one year post-menopausal or three months&#xD;
             post-surgical sterilization. All females of childbearing potential must have a&#xD;
             negative urine pregnancy test result at the screening examination and must not intend&#xD;
             to become pregnant during the study..&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Theresa Heah, MD</last_name>
    <role>Study Director</role>
    <affiliation>Aerie Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aerie Pharmaceuticals</name>
      <address>
        <city>Bedminster</city>
        <state>New Jersey</state>
        <zip>07921</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <results_first_submitted>January 17, 2018</results_first_submitted>
  <results_first_submitted_qc>March 9, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">April 6, 2018</results_first_posted>
  <disposition_first_submitted>July 11, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>July 11, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">July 13, 2016</disposition_first_posted>
  <last_update_submitted>March 9, 2018</last_update_submitted>
  <last_update_submitted_qc>March 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glaucoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glaucoma</mesh_term>
    <mesh_term>Glaucoma, Open-Angle</mesh_term>
    <mesh_term>Ocular Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Timolol</mesh_term>
    <mesh_term>Pharmaceutical Solutions</mesh_term>
    <mesh_term>Ophthalmic Solutions</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>62 clinical trial sites participated in this study, of which 60 clinical trial sites enrolled participants. Screening started in June 2014. Enrollment started in July 2014. The last participant was enrolled in March 2015.</recruitment_details>
      <pre_assignment_details>Prior to enrollment, adult participants were required to have a Screening Visit and 2 Qualification Visits to allow for washout of ocular hypotensive medication.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AR-13324 Ophthalmic Solution 0.02% &amp; Placebo</title>
          <description>1 drop AR-13324 in the evening (PM) and 1 drop placebo in the morning (AM) in both eyes (OU)</description>
        </group>
        <group group_id="P2">
          <title>Timolol Maleate Ophthalmic Solution 0.5% BID</title>
          <description>1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)</description>
        </group>
        <group group_id="P3">
          <title>AR-13324 Ophthalmic Solution 0.02% BID</title>
          <description>1 drop AR-13324 twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="251"/>
                <participants group_id="P2" count="251"/>
                <participants group_id="P3" count="254"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="146"/>
                <participants group_id="P2" count="204"/>
                <participants group_id="P3" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="105"/>
                <participants group_id="P2" count="47"/>
                <participants group_id="P3" count="168"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="71"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="132"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-Compliant</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disallowed Concurrent Medication</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other(Site,Sponsor and Subject request)</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The randomized population includes all subjects who were randomized to treatment. Baseline variables and demographic characteristics were summarized for this population.</population>
      <group_list>
        <group group_id="B1">
          <title>AR-13324 Ophthalmic Solution 0.02% &amp; Placebo</title>
          <description>1 drop AR-13324 in the evening (PM) and 1 drop placebo in the morning (AM) in both eyes (OU)</description>
        </group>
        <group group_id="B2">
          <title>Timolol Maleate Ophthalmic Solution 0.5% BID</title>
          <description>1 drop Timolol maleate twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)</description>
        </group>
        <group group_id="B3">
          <title>AR-13324 Ophthalmic Solution 0.02% BID</title>
          <description>1 drop AR-13324 twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)</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="251"/>
            <count group_id="B2" value="251"/>
            <count group_id="B3" value="254"/>
            <count group_id="B4" value="756"/>
          </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="65.3" spread="11.48"/>
                    <measurement group_id="B2" value="63" spread="11.81"/>
                    <measurement group_id="B3" value="64.1" spread="12.46"/>
                    <measurement group_id="B4" value="64.1" spread="11.95"/>
                  </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="148"/>
                    <measurement group_id="B2" value="150"/>
                    <measurement group_id="B3" value="165"/>
                    <measurement group_id="B4" value="463"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="103"/>
                    <measurement group_id="B2" value="101"/>
                    <measurement group_id="B3" value="89"/>
                    <measurement group_id="B4" value="293"/>
                  </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="41"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="43"/>
                    <measurement group_id="B4" value="126"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="210"/>
                    <measurement group_id="B2" value="209"/>
                    <measurement group_id="B3" value="211"/>
                    <measurement group_id="B4" value="630"/>
                  </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>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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="14"/>
                  </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="69"/>
                    <measurement group_id="B2" value="76"/>
                    <measurement group_id="B3" value="69"/>
                    <measurement group_id="B4" value="214"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="178"/>
                    <measurement group_id="B2" value="166"/>
                    <measurement group_id="B3" value="177"/>
                    <measurement group_id="B4" value="521"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Intraocular Pressure (IOP)</title>
        <description>The primary efficacy outcome is mean intraocular pressure (IOP)</description>
        <time_frame>3 months</time_frame>
        <population>The Per Protocol (PP) population includes all subjects who did not have a major protocol violation likely to seriously affect the primary outcome of the study. This is the primary population for efficacy analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>AR-13324 Ophthalmic Solution 0.02% &amp; Placebo</title>
            <description>1 drop AR-13324 in the PM &amp; 1 drop placebo in the AM, OU</description>
          </group>
          <group group_id="O2">
            <title>Timolol Maleate Ophthalmic Solution 0.5% BID</title>
            <description>1 drop Timolol maleate BID in the AM and PM, OU</description>
          </group>
          <group group_id="O3">
            <title>AR-13324 Ophthalmic Solution 0.02% BID</title>
            <description>1 drop AR-13324 BID in the AM and PM, OU</description>
          </group>
        </group_list>
        <measure>
          <title>Intraocular Pressure (IOP)</title>
          <description>The primary efficacy outcome is mean intraocular pressure (IOP)</description>
          <population>The Per Protocol (PP) population includes all subjects who did not have a major protocol violation likely to seriously affect the primary outcome of the study. This is the primary population for efficacy analyses.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="206"/>
                <count group_id="O2" value="217"/>
                <count group_id="O3" value="209"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1, 0800 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.51" spread="1.654"/>
                    <measurement group_id="O2" value="23.45" spread="1.601"/>
                    <measurement group_id="O3" value="23.50" spread="1.671"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1, 1000 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.31" spread="2.131"/>
                    <measurement group_id="O2" value="22.18" spread="2.089"/>
                    <measurement group_id="O3" value="22.26" spread="2.103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1, 1600 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.56" spread="2.338"/>
                    <measurement group_id="O2" value="21.61" spread="2.369"/>
                    <measurement group_id="O3" value="21.49" spread="2.279"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15, 0800 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.01" spread="2.979"/>
                    <measurement group_id="O2" value="18.25" spread="2.736"/>
                    <measurement group_id="O3" value="18.20" spread="3.491"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15, 1000 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.74" spread="3.089"/>
                    <measurement group_id="O2" value="17.49" spread="2.796"/>
                    <measurement group_id="O3" value="16.91" spread="3.087"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15, 1600 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.37" spread="2.830"/>
                    <measurement group_id="O2" value="17.59" spread="2.935"/>
                    <measurement group_id="O3" value="16.28" spread="2.925"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 43, 0800 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.37" spread="3.749"/>
                    <measurement group_id="O2" value="18.08" spread="2.614"/>
                    <measurement group_id="O3" value="18.57" spread="3.206"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 43, 1000 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.10" spread="3.335"/>
                    <measurement group_id="O2" value="17.31" spread="2.805"/>
                    <measurement group_id="O3" value="17.09" spread="3.028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 43, 1600 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.88" spread="2.888"/>
                    <measurement group_id="O2" value="17.25" spread="2.813"/>
                    <measurement group_id="O3" value="16.58" spread="3.095"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 90 (Month 3), 0800 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.43" spread="3.761"/>
                    <measurement group_id="O2" value="18.21" spread="2.819"/>
                    <measurement group_id="O3" value="18.66" spread="3.460"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 90 (Month 3), 1000 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.18" spread="3.571"/>
                    <measurement group_id="O2" value="17.52" spread="2.777"/>
                    <measurement group_id="O3" value="17.81" spread="3.330"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 90 (Month 3), 1600 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.73" spread="3.386"/>
                    <measurement group_id="O2" value="17.67" spread="2.879"/>
                    <measurement group_id="O3" value="17.08" spread="3.112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Extent of Exposure</title>
        <description>Exposure to study medication in days for all treatment groups</description>
        <time_frame>12 Months</time_frame>
        <population>The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. The safety population summarized subjects as treated for purpose of analysis. One (1) subject did not receive study drug as randomized, shown in the Participant Flow</population>
        <group_list>
          <group group_id="O1">
            <title>AR-13324 Ophthalmic Solution 0.02% &amp; Placebo</title>
            <description>1 drop AR-13324 in the PM and 1 drop placebo in the AM in both eyes</description>
          </group>
          <group group_id="O2">
            <title>Timolol Maleate Ophthalmic Solution 0.5% BID</title>
            <description>1 drop Timolol maleate BID in the AM and PM, OU</description>
          </group>
          <group group_id="O3">
            <title>AR-13324 Ophthalmic Solution 0.02% BID</title>
            <description>1 drop AR-13324 BID in the AM and PM, OU</description>
          </group>
        </group_list>
        <measure>
          <title>Extent of Exposure</title>
          <description>Exposure to study medication in days for all treatment groups</description>
          <population>The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. The safety population summarized subjects as treated for purpose of analysis. One (1) subject did not receive study drug as randomized, shown in the Participant Flow</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="251"/>
                <count group_id="O2" value="251"/>
                <count group_id="O3" value="253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="259.7" spread="133.34"/>
                    <measurement group_id="O2" value="324.5" spread="90.73"/>
                    <measurement group_id="O3" value="185.2" spread="144.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <desc>The Safety Population included all randomized subjects who received at least 1 dose of study medication and was used to summarize safety variables. One (1) subject did not receive study drug as randomized, shown in the Participant Flow.</desc>
      <group_list>
        <group group_id="E1">
          <title>AR-13324 Ophthalmic Solution 0.02% &amp; Placebo</title>
          <description>1 drop AR-13324 in the PM and 1 drop placebo in the AM, OU</description>
        </group>
        <group group_id="E2">
          <title>Timolol Maleate Ophthalmic Solution 0.5% BID</title>
          <description>1 drop Timolol maleate BID in the AM and PM, OU</description>
        </group>
        <group group_id="E3">
          <title>AR-13324 Ophthalmic Solution 0.02% BID</title>
          <description>1 drop AR-13324 BID in the AM and PM, OU</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>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="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Coronary Artery Disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Atrial Fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Atrial Flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Gastric Ulcer Perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Peritonitis Bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Foot Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Postoperative Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Road Traffic Accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Hip Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Ligament Rupture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Tendon Rupture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Prostatic Specific Antigen Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Fluid Overload</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Synovial Cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast Cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Malignant Melanoma in Situ</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Myelodysplastic Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Prostate Cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular Accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Embolic Stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Carotid Artery Stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Renal Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Pulmonary Artery Stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Pulmonary Embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Accelerated Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Internal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Peripheral Artery Occlusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="198" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="96" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="213" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival Hyperaemia</sub_title>
                <counts group_id="E1" subjects_affected="152" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="168" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Cornea Verticillata</sub_title>
                <counts group_id="E1" subjects_affected="64" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="64" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Conjunctival Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="49" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="44" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Lacrimation Increased</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="25" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Visual Acuity Reduced</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="22" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Eye Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Conjunctival Oedema</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Erythema of Eyelid</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Eye Irritation</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Foreign Body Sensation in Eyes</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Instillation Site Pain</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="45" subjects_at_risk="253"/>
              </event>
              <event>
                <sub_title>Instillation Site Erythema</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="32" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Vital Dye Staining Cornea Present</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="251"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Nancy Ramirez-Davis, Director of Clinical Project Management</name_or_title>
      <organization>Aerie Pharmaceuticals, Inc.</organization>
      <phone>908-947-3543</phone>
      <email>nramirez@aeriepharma.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/NCT02207621
org study id: AR-13324-CS302
nct id: NCT02207621
lead sponsor: 
has dmc: No
Evaluation of the ocular hypotensive efficacy and safety of Netarsudil (AR-13324) Ophthalmic
      Solution compared to Timolol Maleate Ophthalmic Solution
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Intraocular Pressure (IOP)
time frame: 3 months
description: The primary efficacy outcome is mean intraocular pressure (IOP)
measure: Extent of Exposure
time frame: 12 Months
description: Exposure to study medication in days for all treatment groups
arm group label: AR-13324 Ophthalmic Solution 0.02% & placebo
arm group type: Experimental
description: 1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU)
arm group label: Timolol maleate Ophthalmic Solution 0.5% BID
arm group type: Active Comparator
description: 1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
arm group label: AR-13324 Ophthalmic Solution 0.02% BID
arm group type: Experimental
description: 1 drop AR-13324 twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
intervention type: Drug
intervention name: AR-13324 Ophthalmic Solution 0.02%
description: 1 drop once daily (QD), PM, OU
arm group label: AR-13324 Ophthalmic Solution 0.02% & placebo
other name: Netarsudil
intervention type: Drug
intervention name: Timolol maleate Ophthalmic Solution 0.5% BID
description: 1 drop BID, AM/PM, OU
arm group label: Timolol maleate Ophthalmic Solution 0.5% BID
intervention type: Other
intervention name: Placebo
description: 1 drop QD, AM, OU
arm group label: AR-13324 Ophthalmic Solution 0.02% & placebo
intervention type: Drug
intervention name: AR-13324 Ophthalmic Solution 0.02% BID
description: 1 drop BID, AM/PM, OU
arm group label: AR-13324 Ophthalmic Solution 0.02% BID
other name: Netarsudil
criteria: 
gender: All
minimum age: N/A
maximum age: 99 Years
healthy volunteers: No
last name: Theresa Heah, MD
role: Study Director
affiliation: Aerie Pharmaceuticals, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glaucoma
mesh term: Glaucoma, Open-Angle
mesh term: Ocular Hypertension
mesh term: Hypertension
mesh term: Timolol
mesh term: Pharmaceutical Solutions
mesh term: Ophthalmic Solutions
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 