<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/NCT03233308</url>
  </required_header>
  <id_info>
    <org_study_id>AR-13324-CS206</org_study_id>
    <nct_id>NCT03233308</nct_id>
  </id_info>
  <brief_title>Study of Netarsudil Ophthalmic Solution in Subjects With Primary Open Angle Glaucoma (POAG) or Ocular Hypertension (OHT)</brief_title>
  <official_title>A Double-Masked, Randomized, Placebo-Controlled Study of Trabecular Outflow Facility Following Treatment With Netarsudil Ophthalmic Solution 0.02% (AR-13324) in Subjects 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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the effect on trabecular outflow facility of Netarsudil ophthalmic solution 0.02%&#xD;
      compared to placebo&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Trabecular outflow facility is a measure of aqueous humor dynamics; effect of netarsudil on&#xD;
      this parameter as well as on intraocular pressure and episcleral venous pressure was&#xD;
      evaluated in this study. Netarsudil treatment was given in one eye and placebo given in&#xD;
      contralateral eye for 7 consecutive days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 20, 2017</start_date>
  <completion_date type="Actual">April 19, 2018</completion_date>
  <primary_completion_date type="Actual">April 19, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Paired comparison study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility</measure>
    <time_frame>Study treatment was administered for 7 days, and outcome measures collected on Day 8</time_frame>
    <description>Mean diurnal change from baseline in trabecular (tonographic) outflow facility.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility.</measure>
    <time_frame>Study treatment was administered for 7 days, and outcome measures collected on Day 8</time_frame>
    <description>Mean diurnal change from baseline in trabecular (tonographic) outflow facility.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)</measure>
    <time_frame>Study treatment was administered for 7 days, and outcome measures collected on Day 8</time_frame>
    <description>Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)</measure>
    <time_frame>Study treatment was administered for 7 days, and outcome measures collected on Day 8</time_frame>
    <description>Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Primary Open Angle Glaucoma or Ocular Hypertension</condition>
  <arm_group>
    <arm_group_label>Netarsudil Ophthalmic Solution 0.02%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Netarsudil Ophthalmic Solution 0.02% was administered in one eye and Placebo comparator in contralateral eye</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo comparator administered in one eye and Netarsudil Ophthalmic Solution 0.02% in contralateral eye</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Netarsudil Ophthalmic Solution 0.02%</intervention_name>
    <description>1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye</description>
    <arm_group_label>Netarsudil Ophthalmic Solution 0.02%</arm_group_label>
    <arm_group_label>Placebo Comparator</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Comparator</intervention_name>
    <description>1 drop daily (QD), in the morning (AM) of Placebo comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye</description>
    <arm_group_label>Netarsudil Ophthalmic Solution 0.02%</arm_group_label>
    <arm_group_label>Placebo Comparator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must be 18 years of age or older&#xD;
&#xD;
          2. Diagnosis of open primary angle glaucoma(POAG) or ocular hypertension (OHT) in both&#xD;
             eyes&#xD;
&#xD;
          3. Unmedicated intraocular pressure (IOP) &gt;20 mmHg and &lt; 30 mmHg in both eyes at first&#xD;
             qualification visit&#xD;
&#xD;
          4. Best corrected visual acuity (BCVA) equivalent to 20/200 Snellen or better&#xD;
&#xD;
          5. Able to give informed consent and follow study instructions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Ophthalmic:&#xD;
&#xD;
          1. Clinically significant ocular disease&#xD;
&#xD;
          2. Pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure&#xD;
             glaucoma, or narrow angles&#xD;
&#xD;
          3. Intraocular pressure ≥30 mmHg in either eye&#xD;
&#xD;
          4. A difference in IOP between eyes &gt;4mmHg at qualification visit&#xD;
&#xD;
          5. Use of more than two ocular hypotensive medications within 30 days of screening&#xD;
&#xD;
          6. Known hypersensitivity to any component of the formulation&#xD;
&#xD;
          7. Previous glaucoma surgery or refractive surgery&#xD;
&#xD;
          8. Keratorefractive surgery in either eye&#xD;
&#xD;
          9. Report of ocular injury in either eye within the six months prior to screening or&#xD;
             ocular or non-refractive surgery within 3 months prior to screening&#xD;
&#xD;
         10. Recent or current ocular infection or inflammation in either eye&#xD;
&#xD;
         11. Use of ocular medication in either eye of any kind within 30 days of screening&#xD;
&#xD;
         12. Mean central corneal thickness greater than 620 μm in either eye&#xD;
&#xD;
         13. Any abnormality preventing reliable applanation tonometry of either eye&#xD;
&#xD;
         14. Lack of suitable episcleral vein prior to performing Episcleral Venus Pressure (EVP)&#xD;
             measurement (applicable to 1 site only)&#xD;
&#xD;
             Systemic:&#xD;
&#xD;
         15. Clinically significant abnormalities within 6 weeks prior to screening&#xD;
&#xD;
         16. Clinically significant systemic disease&#xD;
&#xD;
         17. Participation in any investigational study within 60 days prior to screening&#xD;
&#xD;
         18. Use of systemic medication that could have an effect on intraocular pressure within 30&#xD;
             days prior to screening&#xD;
&#xD;
         19. Women of childbearing potential who were pregnant, nursing, planning a pregnancy, or&#xD;
             not using a medically acceptable form of birth control&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nancy Ramirez-Davis</last_name>
    <role>Study Director</role>
    <affiliation>Aerie Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Eye Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <results_first_submitted>April 18, 2019</results_first_submitted>
  <results_first_submitted_qc>May 20, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 11, 2019</results_first_posted>
  <last_update_submitted>July 29, 2019</last_update_submitted>
  <last_update_submitted_qc>July 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aqueous Humor Dynamics</keyword>
  <keyword>Trabecular Outflow</keyword>
  <keyword>Netarsudil</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>Ophthalmic Solutions</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 16, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03233308/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03233308/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>All Randomized Patients</title>
          <description>1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Modified intent-to-treat (mITT) population</population>
      <group_list>
        <group group_id="B1">
          <title>All Randomized Patients</title>
          <description>1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and placebo comparator to the contralateral eye</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="63" spread="12.53"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility</title>
        <description>Mean diurnal change from baseline in trabecular (tonographic) outflow facility.</description>
        <time_frame>Study treatment was administered for 7 days, and outcome measures collected on Day 8</time_frame>
        <population>Modified intent-to-treat (mITT) population</population>
        <group_list>
          <group group_id="O1">
            <title>Netarsudil Ophthalmic Solution 0.02%</title>
            <description>Netarsudil Ophthalmic Solution 0.02% was administered in one eye</description>
          </group>
          <group group_id="O2">
            <title>Placebo Comparator</title>
            <description>Placebo Comparator administered in contralateral eye</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility</title>
          <description>Mean diurnal change from baseline in trabecular (tonographic) outflow facility.</description>
          <population>Modified intent-to-treat (mITT) population</population>
          <units>mcl/min/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="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.039" spread="0.0401"/>
                    <measurement group_id="O2" value="0.007" spread="0.0275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Mean Change from Baseline</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0010</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility.</title>
        <description>Mean diurnal change from baseline in trabecular (tonographic) outflow facility.</description>
        <time_frame>Study treatment was administered for 7 days, and outcome measures collected on Day 8</time_frame>
        <population>Modified intent-to-treat (mITT) population</population>
        <group_list>
          <group group_id="O1">
            <title>Netarsudil Ophthalmic Solution 0.02%</title>
            <description>Netarsudil Ophthalmic Solution 0.02% was administered in one eye</description>
          </group>
          <group group_id="O2">
            <title>Placebo Comparator</title>
            <description>Placebo comparator administered in contralateral eye</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility.</title>
          <description>Mean diurnal change from baseline in trabecular (tonographic) outflow facility.</description>
          <population>Modified intent-to-treat (mITT) population</population>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.589" spread="34.5935"/>
                    <measurement group_id="O2" value="9.597" spread="25.6334"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Mean change from baseline (percent difference from baseline)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0003</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)</title>
        <description>Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)</description>
        <time_frame>Study treatment was administered for 7 days, and outcome measures collected on Day 8</time_frame>
        <population>Modified intent-to-treat (mITT) population, EVP analyzed in 9 participants</population>
        <group_list>
          <group group_id="O1">
            <title>Netarsudil Ophthalmic Solution 0.02%</title>
            <description>Netarsudil Ophthalmic Solution 0.02% administered to one eye and placebo to the contralateral eye</description>
          </group>
          <group group_id="O2">
            <title>Placebo Comparator</title>
            <description>Placebo Comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)</title>
          <description>Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)</description>
          <population>Modified intent-to-treat (mITT) population, EVP analyzed in 9 participants</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="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Diurnal EVP (delta vs.baseline)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.787" spread="0.8372"/>
                    <measurement group_id="O2" value="0.103" spread="0.7094"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diurnal IOP (delta vs.baseline)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.521" spread="1.5842"/>
                    <measurement group_id="O2" value="-0.979" spread="1.6009"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Mean change from baseline -EVP</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0687</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Mean change from baseline -IOP</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)</title>
        <description>Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)</description>
        <time_frame>Study treatment was administered for 7 days, and outcome measures collected on Day 8</time_frame>
        <population>Modified intent-to-treat (mITT) population, EVP analyzed in 9 participants</population>
        <group_list>
          <group group_id="O1">
            <title>Netarsudil Ophthalmic Solution 0.02%</title>
            <description>Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye</description>
          </group>
          <group group_id="O2">
            <title>Placebo Comparator</title>
            <description>Placebo comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)</title>
          <description>Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)</description>
          <population>Modified intent-to-treat (mITT) population, EVP analyzed in 9 participants</population>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Percent change from baseline (EVP)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.465" spread="9.5044"/>
                    <measurement group_id="O2" value="3.103" spread="7.7322"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percent change from baseline (IOP)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.568" spread="6.0713"/>
                    <measurement group_id="O2" value="-4.227" spread="6.9699"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Mean change from baseline (percent difference from baseline) -EVP</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0087</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Mean change from baseline (percent difference from baseline)- IOP</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>7 Days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Netarsudil Ophthalmic Solution 0.02%</title>
          <description>Netarsudil Ophthalmic Solution 0.02% was administered in one eye and Placebo comparator in contralateral eye</description>
        </group>
        <group group_id="E2">
          <title>Placebo Comparator</title>
          <description>Placebo comparator was administered in one eye and Netarsudil Ophthalmic Solution 0.02% in contralateral eye</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</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="13" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival Hyperaemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Eye Irritation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Eye Swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </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>Theresa GH Heah, MD, MBA</name_or_title>
      <organization>Aerie Pharmaceuticals, Inc</organization>
      <phone>908-947-3844</phone>
      <email>theah@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/NCT03233308
org study id: AR-13324-CS206
nct id: NCT03233308
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the effect on trabecular outflow facility of Netarsudil ophthalmic solution 0.02%
      compared to placebo
Trabecular outflow facility is a measure of aqueous humor dynamics; effect of netarsudil on
      this parameter as well as on intraocular pressure and episcleral venous pressure was
      evaluated in this study. Netarsudil treatment was given in one eye and placebo given in
      contralateral eye for 7 consecutive days.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Paired comparison study
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility
time frame: Study treatment was administered for 7 days, and outcome measures collected on Day 8
description: Mean diurnal change from baseline in trabecular (tonographic) outflow facility.
measure: Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility.
time frame: Study treatment was administered for 7 days, and outcome measures collected on Day 8
description: Mean diurnal change from baseline in trabecular (tonographic) outflow facility.
measure: Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)
time frame: Study treatment was administered for 7 days, and outcome measures collected on Day 8
description: Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)
measure: Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)
time frame: Study treatment was administered for 7 days, and outcome measures collected on Day 8
description: Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)
arm group label: Netarsudil Ophthalmic Solution 0.02%
arm group type: Experimental
description: Netarsudil Ophthalmic Solution 0.02% was administered in one eye and Placebo comparator in contralateral eye
arm group label: Placebo Comparator
arm group type: Placebo Comparator
description: Placebo comparator administered in one eye and Netarsudil Ophthalmic Solution 0.02% in contralateral eye
intervention type: Drug
intervention name: Netarsudil Ophthalmic Solution 0.02%
description: 1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye
arm group label: Netarsudil Ophthalmic Solution 0.02%
arm group label: Placebo Comparator
intervention type: Other
intervention name: Placebo Comparator
description: 1 drop daily (QD), in the morning (AM) of Placebo comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye
arm group label: Netarsudil Ophthalmic Solution 0.02%
arm group label: Placebo Comparator
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nancy Ramirez-Davis
role: Study Director
affiliation: Aerie Pharmaceuticals
facility: 
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: Ophthalmic Solutions
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 