<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/NCT03751098</url>
  </required_header>
  <id_info>
    <org_study_id>EYN-MYD-TP-32</org_study_id>
    <nct_id>NCT03751098</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Phenylephrine 2.5%-Tropicamide 1% Microdose Ophthalmic Solution for Pupil Dilation</brief_title>
  <acronym>MIST-2</acronym>
  <official_title>A Multi-Center, Double-Masked, Placebo-Controlled, Phase 3 Study of the Safety and Efficacy of Fixed Combination Phenylephrine 2.5%-Tropicamide 1% Ophthalmic Solution Administered With a Microdose Dispenser for Dilation of the Pupil</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eyenovia Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eyenovia Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluated pupil dilation after administration of fixed combination&#xD;
      tropicamide-phenylephrine (TR/PH) vs. placebo. Participants attended 3 visits. At each visit,&#xD;
      after baseline measurements, either the study drug or placebo was administered to both eyes,&#xD;
      then pupil dilation and safety assessments were performed at specific time intervals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Volunteer participants were screened for study eligibility during a Screening Visit and&#xD;
      enrolled after signing the study-specific informed consent form. Subjects meeting all&#xD;
      inclusion/exclusion criteria were scheduled for 3 treatment visits, which were at least 2&#xD;
      days, but no more than 7 days apart. At each treatment visit, baseline measurements were&#xD;
      taken, then either the study drug or placebo was administered to both eyes. Afterwards,&#xD;
      efficacy and safety assessments were performed at 20, 35, 50, 65, 80, 120, and 180 minutes.&#xD;
      Participants' treatment assignments for each treatment visit were equally randomized using 1&#xD;
      of 2 sequences - ABB or BAA, where A was the study drug and B was the placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Actual">January 21, 2019</completion_date>
  <primary_completion_date type="Actual">January 21, 2019</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>Crossover Assignment</intervention_model>
    <intervention_model_description>This trial was a double-masked, placebo-controlled, cross-over superiority study evaluating the efficacy of the fixed combination drug vs. placebo. All participants in the trial were to receive each treatment.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>There were no differences in the presentation of study treatment administered and all study personnel conducting ophthalmic assessments after study treatment administration were masked to treatment assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Pupil Diameter From Baseline</measure>
    <time_frame>35 minutes after initial dose</time_frame>
    <description>Difference in 35-minute pupil diameter vs. baseline measured using pupillometry in highly photopic conditions.&#xD;
Pupil diameter is reported in millimeters. For the change in pupil diameter, larger measurements indicate a better outcome.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Proportion of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication</measure>
    <time_frame>35 minutes after initial dose</time_frame>
    <description>The percent of eyes with pupil diameter 6.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 69 participants received each medication. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication</measure>
    <time_frame>35 minutes after initial dose</time_frame>
    <description>The percent of eyes with pupil diameter 7.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 69 participants received each solution. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">76</enrollment>
  <condition>Mydriasis</condition>
  <arm_group>
    <arm_group_label>1-TR/PE, 2-Placebo, 3-Placebo</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the designated treatment in each eye.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1-Placebo, 2-Placebo, 3-TR/PE</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the designated treatment in each eye.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tropicamide/Phenylephrine ophthalmic solution (TR/PE)</intervention_name>
    <description>Tropicamide 1%/phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser</description>
    <arm_group_label>1-Placebo, 2-Placebo, 3-TR/PE</arm_group_label>
    <arm_group_label>1-TR/PE, 2-Placebo, 3-Placebo</arm_group_label>
    <other_name>Mydcombi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Eyewash administered with the Optejet microdose dispenser</description>
    <arm_group_label>1-Placebo, 2-Placebo, 3-TR/PE</arm_group_label>
    <arm_group_label>1-TR/PE, 2-Placebo, 3-Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to provide written consent and return for all study visits&#xD;
&#xD;
          -  Photopic pupil diameter &lt;= 3.5 mm in each eye&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to phenylephrine hydrochloride, tropicamide, or benzalkonium chloride&#xD;
&#xD;
          -  History of benign prostatic hyperplasia&#xD;
&#xD;
          -  Use of a benzodiazepine, monoamine oxidase inhibitor, tricyclic antidepressant,&#xD;
             anticonvulsant, or cholinergic drug&#xD;
&#xD;
          -  History of closed-angle glaucoma&#xD;
&#xD;
          -  Anatomically narrow anterior chamber angles&#xD;
&#xD;
          -  Ocular surgery or laser treatment of any kind&#xD;
&#xD;
          -  History of chronic or acute uveitis&#xD;
&#xD;
          -  History of traumatic iritis or hyphema&#xD;
&#xD;
          -  History of traumatic mydriasis or angle recession&#xD;
&#xD;
          -  History of heterochromia&#xD;
&#xD;
          -  Irregularly-shaped pupil secondary to ocular trauma or congenital defect.&#xD;
&#xD;
          -  History of neurogenic pupil disorder&#xD;
&#xD;
          -  History of anterior chamber intraocular lens (IOL) or iris-fixated IOL&#xD;
&#xD;
          -  History of iris surgery, iris atrophy, or iris-cornea apposition/touch&#xD;
&#xD;
          -  Unwilling or unable to discontinue use of contact lenses at treatment visits.&#xD;
&#xD;
          -  Current active eye disease for which topical or systemic ophthalmic medication is&#xD;
             necessary, except for dry eye disease managed using artificial tears.&#xD;
&#xD;
          -  Presence of a severe/serious ocular condition, or any other unstable medical condition&#xD;
             that, in the Investigator's opinion, may preclude study treatment and/or follow-up&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tsontcho Ianchulev, MD, MPH</last_name>
    <role>Study Director</role>
    <affiliation>Eyenovia Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Keystone Research</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>R&amp;R Research</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>November 14, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <results_first_submitted>January 27, 2022</results_first_submitted>
  <results_first_submitted_qc>March 16, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 18, 2022</results_first_posted>
  <disposition_first_submitted>January 31, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>March 16, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 18, 2022</disposition_first_posted>
  <last_update_submitted>March 16, 2022</last_update_submitted>
  <last_update_submitted_qc>March 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mydriasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phenylephrine</mesh_term>
    <mesh_term>Oxymetazoline</mesh_term>
    <mesh_term>Ophthalmic Solutions</mesh_term>
    <mesh_term>Tropicamide</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>November 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03751098/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>January 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03751098/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 30, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03751098/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>76 patients signed the study informed consent form and were screened for eligibility between November 19, 2018 and December 14, 2018 at clinical research centers located in San Antonio and Austin, Texas.</recruitment_details>
      <pre_assignment_details>70 of the 76 participants enrolled initiated study treatment. Of those who did not initiate treatment, 4 failed to meet all study eligibility criteria and 2 were exited after screening (before treatment) because the required number of subjects had initiated treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>1-TR/PE, 2-Placebo, 3-Placebo</title>
          <description>Participants were administered the assigned treatment in each eye on separate days in the following order: 1st Treatment Day: Tropicamide 1%/Phenylephrine 2.5%, 2nd Treatment Day: Placebo, 3rd Treatment Day: Placebo. Each treatment was administered with the Optejet microdose dispenser.</description>
        </group>
        <group group_id="P2">
          <title>1-Placebo, 2-Placebo, 3-TR/PE</title>
          <description>Participants were administered the assigned treatment in each eye on separate days in the following order: 1st Treatment Day: Placebo, 2nd Treatment Day: Placebo, 3rd Treatment Day: Tropicamide 1%/Placebo 2.5%. Each treatment was administered with the Optejet microdose dispenser.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>Participants were administered the assigned treatments on 3 separate days (treatment administration sequence was randomized).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="70"/>
          </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="35.4" spread="14.55"/>
                  </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="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                  </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="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </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="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="62"/>
                  </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>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Iris Color Category</title>
          <description>Dark = Brown/black irides Light = All other colors</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Dark</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Light</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Pupil Diameter From Baseline</title>
        <description>Difference in 35-minute pupil diameter vs. baseline measured using pupillometry in highly photopic conditions.&#xD;
Pupil diameter is reported in millimeters. For the change in pupil diameter, larger measurements indicate a better outcome.</description>
        <time_frame>35 minutes after initial dose</time_frame>
        <population>Per-protocol population (participants who completed all planned assessments without a major protocol deviation)</population>
        <group_list>
          <group group_id="O1">
            <title>TR/PE - Right Eye</title>
            <description>Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O2">
            <title>TR/PE - Left Eye</title>
            <description>Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser.</description>
          </group>
          <group group_id="O3">
            <title>Placebo - Right Eye</title>
            <description>Placebo ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Left Eye</title>
            <description>Placebo ophthalmic solution administered to the left eye with the Optejet microdose dispenser</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pupil Diameter From Baseline</title>
          <description>Difference in 35-minute pupil diameter vs. baseline measured using pupillometry in highly photopic conditions.&#xD;
Pupil diameter is reported in millimeters. For the change in pupil diameter, larger measurements indicate a better outcome.</description>
          <population>Per-protocol population (participants who completed all planned assessments without a major protocol deviation)</population>
          <units>millimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="69"/>
                <count group_id="O3" value="69"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="69"/>
                <count group_id="O3" value="69"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change in 35-minute pupil diameter</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.747" spread="0.7301"/>
                    <measurement group_id="O2" value="4.779" spread="0.8032"/>
                    <measurement group_id="O3" value="0.134" spread="0.4972"/>
                    <measurement group_id="O4" value="0.032" spread="0.4983"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline pupil diameter</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.597" spread="0.4784"/>
                    <measurement group_id="O2" value="2.524" spread="0.4802"/>
                    <measurement group_id="O3" value="2.632" spread="0.5202"/>
                    <measurement group_id="O4" value="2.559" spread="0.4666"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>35-minutes pupil diameter</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.344" spread="0.7981"/>
                    <measurement group_id="O2" value="7.304" spread="0.8264"/>
                    <measurement group_id="O3" value="2.766" spread="0.6598"/>
                    <measurement group_id="O4" value="2.590" spread="0.5892"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Proportion of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication</title>
        <description>The percent of eyes with pupil diameter 6.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 69 participants received each medication. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome.</description>
        <time_frame>35 minutes after initial dose</time_frame>
        <population>Per-protocol population (participants who completed all planned assessments without a major protocol deviation)</population>
        <group_list>
          <group group_id="O1">
            <title>TR/PE - Right Eye</title>
            <description>Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O2">
            <title>TR/PE - Left Eye</title>
            <description>Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser.</description>
          </group>
          <group group_id="O3">
            <title>Placebo - Right Eye</title>
            <description>Placebo ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Left Eye</title>
            <description>Placebo ophthalmic solution administered to the left eye with the Optejet microdose dispenser</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication</title>
          <description>The percent of eyes with pupil diameter 6.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 69 participants received each medication. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome.</description>
          <population>Per-protocol population (participants who completed all planned assessments without a major protocol deviation)</population>
          <units>percentage of eyes</units>
          <param>Number</param>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="69"/>
                <count group_id="O3" value="69"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="69"/>
                <count group_id="O3" value="69"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.8"/>
                    <measurement group_id="O2" value="94.2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Proportion of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication</title>
        <description>The percent of eyes with pupil diameter 7.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 69 participants received each solution. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome.</description>
        <time_frame>35 minutes after initial dose</time_frame>
        <population>Per-protocol population (participants who completed all planned assessments without a major protocol deviation)</population>
        <group_list>
          <group group_id="O1">
            <title>TR/PE - Right Eye</title>
            <description>Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O2">
            <title>TR/PE - Left Eye</title>
            <description>Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser.</description>
          </group>
          <group group_id="O3">
            <title>Placebo - Right Eye</title>
            <description>Placebo ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O4">
            <title>Placebo - Left Eye</title>
            <description>Placebo ophthalmic solution administered to the left eye with the Optejet microdose dispenser</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication</title>
          <description>The percent of eyes with pupil diameter 7.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 69 participants received each solution. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome.</description>
          <population>Per-protocol population (participants who completed all planned assessments without a major protocol deviation)</population>
          <units>percentage of eyes</units>
          <param>Number</param>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="69"/>
                <count group_id="O3" value="69"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="69"/>
                <count group_id="O3" value="69"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.6"/>
                    <measurement group_id="O2" value="68.1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected over each participant's study participation period, which was a maximum of 14 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tropicamide/Phenylephrine</title>
          <description>Tropicamide 1%/Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo ophthalmic solution administered with the Optejet microdose dispenser</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="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.0</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="2" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Instillation site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="70"/>
              </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>VP, Development</name_or_title>
      <organization>Eyenovia, Inc.</organization>
      <phone>714-269-8838</phone>
      <email>gclasby@eyenoviabio.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/NCT03751098
org study id: EYN-MYD-TP-32
nct id: NCT03751098
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study evaluated pupil dilation after administration of fixed combination
      tropicamide-phenylephrine (TR/PH) vs. placebo. Participants attended 3 visits. At each visit,
      after baseline measurements, either the study drug or placebo was administered to both eyes,
      then pupil dilation and safety assessments were performed at specific time intervals.
Volunteer participants were screened for study eligibility during a Screening Visit and
      enrolled after signing the study-specific informed consent form. Subjects meeting all
      inclusion/exclusion criteria were scheduled for 3 treatment visits, which were at least 2
      days, but no more than 7 days apart. At each treatment visit, baseline measurements were
      taken, then either the study drug or placebo was administered to both eyes. Afterwards,
      efficacy and safety assessments were performed at 20, 35, 50, 65, 80, 120, and 180 minutes.
      Participants' treatment assignments for each treatment visit were equally randomized using 1
      of 2 sequences - ABB or BAA, where A was the study drug and B was the placebo.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This trial was a double-masked, placebo-controlled, cross-over superiority study evaluating the efficacy of the fixed combination drug vs. placebo. All participants in the trial were to receive each treatment.
primary purpose: Diagnostic
masking: Double (Participant, Outcomes Assessor)
masking description: There were no differences in the presentation of study treatment administered and all study personnel conducting ophthalmic assessments after study treatment administration were masked to treatment assignment.
measure: Change in Pupil Diameter From Baseline
time frame: 35 minutes after initial dose
description: Difference in 35-minute pupil diameter vs. baseline measured using pupillometry in highly photopic conditions.
Pupil diameter is reported in millimeters. For the change in pupil diameter, larger measurements indicate a better outcome.
measure: Proportion of Eyes Achieving Pupil Diameter 6.0 mm or Larger After Receipt of Each Medication
time frame: 35 minutes after initial dose
description: The percent of eyes with pupil diameter 6.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 69 participants received each medication. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome.
measure: Proportion of Eyes Achieving Pupil Diameter 7.0 mm or Larger After Receipt of Each Medication
time frame: 35 minutes after initial dose
description: The percent of eyes with pupil diameter 7.0 mm or larger as measured using pupillometry in highly photopic conditions. As this is a cross-over study, each of the 69 participants received each solution. Data is reported separately for the right and left eyes of the 69 participants. A higher percentage indicates a better outcome.
arm group label: 1-TR/PE, 2-Placebo, 3-Placebo
arm group type: Other
description: Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the designated treatment in each eye.
arm group label: 1-Placebo, 2-Placebo, 3-TR/PE
arm group type: Other
description: Participants were dosed once at 3 separate clinic visits in accordance with this sequence. Each participant received 2 sprays of the designated treatment in each eye.
intervention type: Drug
intervention name: Tropicamide/Phenylephrine ophthalmic solution (TR/PE)
description: Tropicamide 1%/phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
arm group label: 1-Placebo, 2-Placebo, 3-TR/PE
arm group label: 1-TR/PE, 2-Placebo, 3-Placebo
other name: Mydcombi
intervention type: Drug
intervention name: Placebo
description: Eyewash administered with the Optejet microdose dispenser
arm group label: 1-Placebo, 2-Placebo, 3-TR/PE
arm group label: 1-TR/PE, 2-Placebo, 3-Placebo
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Tsontcho Ianchulev, MD, MPH
role: Study Director
affiliation: Eyenovia Inc.
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Mydriasis
mesh term: Phenylephrine
mesh term: Oxymetazoline
mesh term: Ophthalmic Solutions
mesh term: Tropicamide
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 