<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/NCT02246764</url>
  </required_header>
  <id_info>
    <org_study_id>AR-13324-CS303</org_study_id>
    <nct_id>NCT02246764</nct_id>
  </id_info>
  <brief_title>Study of Netarsudil (AR-13324) Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension</brief_title>
  <official_title>A Double-masked, Randomized, Multi-center, Active-controlled, Parallel, 12-month Study Assessing the Safety of AR-13324 Ophthalmic Solution, 0.02% QD &amp; BID Compared to Timolol Maleate Ophthalmic Solution, 0.5% BID 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>
      The purpose of this study is to evaluate the ocular and systemic safety of Netarsudil&#xD;
      (AR-13324) Ophthalmic Solution, 0.02% q.d. and b.i.d. for 12 months compared to the active&#xD;
      comparator Timolol Maleate Ophthalmic Solution, 0.5%.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 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>Extent of Exposure</measure>
    <time_frame>12 months</time_frame>
    <description>Exposure to study medication in days for all treatment groups</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">93</enrollment>
  <condition>Ocular Hypertension</condition>
  <condition>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) and 1 drop placebo in the morning (AM) 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>
  <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 Timolol maleate 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>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>
  <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>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 19 years of age or greater.&#xD;
&#xD;
          2. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT).&#xD;
&#xD;
          3. Unmedicated (post-washout) IOP (Intraocular Pressure) &gt;20 mm Hg and &lt; 27 mm Hg in the&#xD;
             study eye at 2 qualification visits (08:00 hr), 2-7 days apart. At second&#xD;
             qualification visit, IOP &gt; 17 mm Hg and &lt; 27 mm Hg at 10:00 and 16:00 hrs (in the same&#xD;
             eye).&#xD;
&#xD;
          4. Corrected visual acuity in each eye +1.0 logMAR or better by ETDRS (Early Treatment&#xD;
             Diabetic Retinopathy Study) in each eye (equivalent to 20/200).&#xD;
&#xD;
          5. Able and willing to give signed informed consent and follow study instructions.&#xD;
&#xD;
        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 (individuals who are&#xD;
             excluded for this criterion are not allowed to attempt requalification), or use of&#xD;
             more than two ocular hypotensive medications within 30 days of screening. Note: fixed&#xD;
             dose 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 β-adrenoceptor antagonists.&#xD;
&#xD;
          4. Previous glaucoma intraocular surgery or glaucoma laser procedures in either eye.&#xD;
&#xD;
          5. Refractive surgery in either eye (e.g., radial keratotomy, PRK (photorefractive&#xD;
             keratectomy), LASIK (laser eye surgery), corneal cross-linking, etc.).&#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, with the&#xD;
             exception of a) ocular hypotensive medications (which must be washed out according to&#xD;
             the provided schedule), b) lid scrubs (which may be used prior to, but not after&#xD;
             screening) or c) lubricating drops for dry eye (which may be used throughout the&#xD;
             study).&#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 (e.g., cup-disc ratio &gt; 0.8, severe visual field defect).&#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 IOP within 30 days prior&#xD;
             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>19 Years</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</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nancy Ramirez</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>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 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>January 11, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>January 11, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 12, 2018</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>Ocular hypertension.</keyword>
  <keyword>Glaucoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glaucoma</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>
      <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) &amp; 1 drop placebo in the morning (AM) in both eyes (OU)</description>
        </group>
        <group group_id="P2">
          <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="P3">
          <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_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="36"/>
                <participants group_id="P3" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="29"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disallowed Concomitant Medication</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Randomized 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>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="B3">
          <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="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="34"/>
            <count group_id="B2" value="36"/>
            <count group_id="B3" value="23"/>
            <count group_id="B4" value="93"/>
          </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="64.6" spread="7.73"/>
                    <measurement group_id="B2" value="64.4" spread="7.84"/>
                    <measurement group_id="B3" value="61.9" spread="12.52"/>
                    <measurement group_id="B4" value="63.8" spread="9.14"/>
                  </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="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="49"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="91"/>
                  </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="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="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                  </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="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="83"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </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>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</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>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <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="O2">
            <title>AR-13324 Ophthalmic Solution 0.02% BID</title>
            <description>1 drop AR-13324 twice daily (BID) in the morning and evening (PM) in both eyes (OU)</description>
          </group>
          <group group_id="O3">
            <title>Timolol Maleate Ophthalmic Solution 0.5% BID</title>
            <description>1 drop Timolol maleate twice daily (BID) in the morning and evening (PM) in both eyes (OU)</description>
          </group>
        </group_list>
        <measure>
          <title>Extent of Exposure</title>
          <description>Exposure to study medication in days for all treatment groups</description>
          <population>Safety Population</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="34"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="224.4" spread="137.28"/>
                    <measurement group_id="O2" value="101.8" spread="105.69"/>
                    <measurement group_id="O3" value="314.6" spread="111.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year (12 months)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AR-13324 Ophthalmic Solution 0.02% &amp; Placebo</title>
          <description>1 drop AR-13324 in the evening (PM) &amp; 1 drop placebo in the morning (AM) in both eyes (OU)</description>
        </group>
        <group group_id="E2">
          <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="E3">
          <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_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="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Anterior Uveitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </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="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </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="33" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival Hyperaemia</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Corneal Verticillata</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Erythema of Eyelid</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Conjunctival Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eyelid Oedema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Lacrimation Increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Corneal Opacity</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Conjunctival Oedema</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eye Pruritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eye Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eye Irritation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eyelids Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Foreign Body Sensation in Eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Lenticular Opacities</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Conjunctivochalasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eye Discharge</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Conjunctivitis Allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eye Allergy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Eyelid Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Optic Disc Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </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="9" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Instillation Site Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Instillation Site Erythema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Instillation Site Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </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="34"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Intraocular Pressure Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Blood Triglycerides Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis Allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="36"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </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>Enrollment was discontinued after 93 participants were enrolled due to slow enrollment; all participants who entered the study were followed until study completion.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Nancy Ramirez-Davis, Director 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/NCT02246764
org study id: AR-13324-CS303
nct id: NCT02246764
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the ocular and systemic safety of Netarsudil
      (AR-13324) Ophthalmic Solution, 0.02% q.d. and b.i.d. for 12 months compared to the active
      comparator Timolol Maleate Ophthalmic Solution, 0.5%.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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) and 1 drop placebo in the morning (AM) 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)
arm group label: Timolol maleate Ophthalmic Solution 0.5% BID
arm group type: Active Comparator
description: 1 drop Timolol maleate 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: 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
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
criteria: 
gender: All
minimum age: 19 Years
maximum age: 99 Years
healthy volunteers: No
last name: Theresa Heah, MD
role: Study Director
affiliation: Aerie Pharmaceuticals
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glaucoma
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: 
limitations and caveats: Enrollment was discontinued after 93 participants were enrolled due to slow enrollment; all participants who entered the study were followed until study completion.
point of contact: 