<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/NCT03751631</url>
  </required_header>
  <id_info>
    <org_study_id>EYN-MYD-TP-31</org_study_id>
    <nct_id>NCT03751631</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-1</acronym>
  <official_title>A Double-Masked, Active-Controlled Study of the Safety and Efficacy of 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/PE) vs. phenylephrine (PE) alone and tropicamide (TR) alone.&#xD;
      Participants attended 3 visits. At each visit, after baseline measurements, 1 of the 3 drugs&#xD;
      was administered to both eyes, then pupil dilation and safety assessments were performed at&#xD;
      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 1 of the 3 study drugs was administered to both eyes (each participant's drug&#xD;
      administration sequence was randomly determined). Afterwards, efficacy and safety assessments&#xD;
      were performed at 20, 35, 50, 65, 80, 120, and 180 minutes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 15, 2018</start_date>
  <completion_date type="Actual">January 11, 2019</completion_date>
  <primary_completion_date type="Actual">January 11, 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, active-controlled, cross-over superiority study evaluating the efficacy of the fixed combination drug vs. the drug's 2 individual components. All participants in the trial were to receive each of the 3 drugs.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>There were no differences in the presentation of drug administered and all study personnel conducting ophthalmic assessments after drug 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>Percentage 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 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 participants. A higher percentage indicates a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Percentage 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 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 participants. A higher percentage indicates a better outcome.</description>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Mydriasis</condition>
  <arm_group>
    <arm_group_label>1-TR/PE, 2-TR, 3-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 study drug in each eye.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1-TR/PE, 2-PE, 3-TR</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 study drug in each eye.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1-TR, 2-TR/PE, 3-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 study drug in each eye.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1-TR, 2-PE, 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 study drug in each eye.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1-PE, 2-TR/PE, 3-TR</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 study drug in each eye.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1-PE, 2-TR, 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 study drug in each eye.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)</intervention_name>
    <description>Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser</description>
    <arm_group_label>1-PE, 2-TR, 3-TR/PE</arm_group_label>
    <arm_group_label>1-PE, 2-TR/PE, 3-TR</arm_group_label>
    <arm_group_label>1-TR, 2-PE, 3-TR/PE</arm_group_label>
    <arm_group_label>1-TR, 2-TR/PE, 3-PE</arm_group_label>
    <arm_group_label>1-TR/PE, 2-PE, 3-TR</arm_group_label>
    <arm_group_label>1-TR/PE, 2-TR, 3-PE</arm_group_label>
    <other_name>Mydcombi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tropicamide 1% ophthalmic solution (TR)</intervention_name>
    <description>Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser</description>
    <arm_group_label>1-PE, 2-TR, 3-TR/PE</arm_group_label>
    <arm_group_label>1-PE, 2-TR/PE, 3-TR</arm_group_label>
    <arm_group_label>1-TR, 2-PE, 3-TR/PE</arm_group_label>
    <arm_group_label>1-TR, 2-TR/PE, 3-PE</arm_group_label>
    <arm_group_label>1-TR/PE, 2-PE, 3-TR</arm_group_label>
    <arm_group_label>1-TR/PE, 2-TR, 3-PE</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phenylephrine 2.5% ophthalmic solution (PE)</intervention_name>
    <description>Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser</description>
    <arm_group_label>1-PE, 2-TR, 3-TR/PE</arm_group_label>
    <arm_group_label>1-PE, 2-TR/PE, 3-TR</arm_group_label>
    <arm_group_label>1-TR, 2-PE, 3-TR/PE</arm_group_label>
    <arm_group_label>1-TR, 2-TR/PE, 3-PE</arm_group_label>
    <arm_group_label>1-TR/PE, 2-PE, 3-TR</arm_group_label>
    <arm_group_label>1-TR/PE, 2-TR, 3-PE</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>WCCT</name>
      <address>
        <city>Cypress</city>
        <state>California</state>
        <zip>90630</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 21, 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>Pharmaceutical Solutions</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>September 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT03751631/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 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT03751631/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>October 31, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT03751631/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>70 patients signed the study informed consent form and were screened for eligibility between October 31, 2018 and November 16, 2018 at a clinical research center located in Cypress, California.</recruitment_details>
      <pre_assignment_details>64 of the 70 participants enrolled initiated treatment. Of those who did not initiate treatment, 4 failed to meet all study eligibility criteria, 1 was exited during screening due to behavioral issues, and 1 was exited after screening (before treatment) because the investigator believed the required number of subjects had initiated treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>TR/PE - TR - PE</title>
          <description>Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Tropicamide 1%-Phenylephrine 2.5%; 2nd Treatment Day - Tropicamide 1%; 3rd Treatment Day - Phenylephrine 2.5%. Each drug was administered with the Optejet microdose dispenser.</description>
        </group>
        <group group_id="P2">
          <title>TR/PE - PE - TR</title>
          <description>Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Tropicamide 1%-Phenylephrine 2.5%; 2nd Treatment Day - Phenylephrine 2.5%; 3rd Treatment Day - Tropicamide 1%. Each drug was administered with the Optejet microdose dispenser.</description>
        </group>
        <group group_id="P3">
          <title>TR - TR/PE - PE</title>
          <description>Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Tropicamide 1%; 2nd Treatment Day - Tropicamide 1%-Phenylephrine 2.5%; 3rd Treatment Day - Phenylephrine 2.5%. Each drug was administered with the Optejet microdose dispenser.</description>
        </group>
        <group group_id="P4">
          <title>TR - PE - TR/PE</title>
          <description>Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Tropicamide 1%; 2nd Treatment Day - Phenylephrine 2.5%; 3rd Treatment Day - Tropicamide 1%-Phenylephrine 2.5%. Each drug was administered with the Optejet microdose dispenser.</description>
        </group>
        <group group_id="P5">
          <title>PE - TR/PE - TR</title>
          <description>Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Phenylephrine 2.5%; 2nd Treatment Day - Tropicamide 1%-Phenylephrine 2.5%; 3rd Treatment Day - Tropicamide 1%. Each drug was administered with the Optejet microdose dispenser.</description>
        </group>
        <group group_id="P6">
          <title>PE - TR - TR/PE</title>
          <description>Participants were administered the assigned study drug in each eye on separate days in the following order: 1st Treatment Day - Phenylephrine 2.5%; 2nd Treatment Day - Tropicamide 1%; 3rd Treatment Day - Tropicamide 1%-Phenylephrine 2.5%. Each drug 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="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="11"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received 1st Drug in Sequence</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="11"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received 2nd Drug in Sequence</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received 3rd Drug in Sequence</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </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="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </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 each of the 3 assigned drugs on 3 separate days in the clinic (drug administration sequence was equally randomized across 6 possible administration sequences).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="64"/>
          </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="39.4" spread="12.00"/>
                  </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="27"/>
                  </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="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                  </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="8"/>
                  </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="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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="64"/>
                  </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="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Light</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </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>TR - Right Eye</title>
            <description>Tropicamide 1% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O4">
            <title>TR - Left Eye</title>
            <description>Tropicamide 1% ophthalmic solution administered to the left eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O5">
            <title>PE - Right Eye</title>
            <description>Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O6">
            <title>PE - Left Eye</title>
            <description>Phenylephrine 2.5% 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>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="62"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline pupil diameter</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.672" spread="0.5673"/>
                    <measurement group_id="O2" value="2.583" spread="0.4674"/>
                    <measurement group_id="O3" value="2.657" spread="0.6016"/>
                    <measurement group_id="O4" value="2.569" spread="0.5211"/>
                    <measurement group_id="O5" value="2.651" spread="0.5749"/>
                    <measurement group_id="O6" value="2.584" spread="0.5344"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>35-minute pupil diameter</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.301" spread="0.8943"/>
                    <measurement group_id="O2" value="7.329" spread="0.9771"/>
                    <measurement group_id="O3" value="6.762" spread="0.8619"/>
                    <measurement group_id="O4" value="6.690" spread="0.8682"/>
                    <measurement group_id="O5" value="3.388" spread="0.8950"/>
                    <measurement group_id="O6" value="3.552" spread="0.9340"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in 35-minute pupil diameter</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.629" spread="0.8343"/>
                    <measurement group_id="O2" value="4.746" spread="0.8173"/>
                    <measurement group_id="O3" value="4.105" spread="0.7207"/>
                    <measurement group_id="O4" value="4.121" spread="0.6839"/>
                    <measurement group_id="O5" value="0.737" spread="0.7939"/>
                    <measurement group_id="O6" value="0.969" spread="0.8943"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage 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 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 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>TR - Right Eye</title>
            <description>Tropicamide 1% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O4">
            <title>TR - Left Eye</title>
            <description>Tropicamide 1% ophthalmic solution administered to the left eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O5">
            <title>PE - Right Eye</title>
            <description>Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O6">
            <title>PE - Left Eye</title>
            <description>Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage 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 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 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="62"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="62"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="62"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="62"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.2"/>
                    <measurement group_id="O2" value="93.5"/>
                    <measurement group_id="O3" value="79.0"/>
                    <measurement group_id="O4" value="77.4"/>
                    <measurement group_id="O5" value="1.6"/>
                    <measurement group_id="O6" value="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage 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 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 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>TR - Right Eye</title>
            <description>Tropicamide 1% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O4">
            <title>TR - Left Eye</title>
            <description>Tropicamide 1% ophthalmic solution administered to the left eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O5">
            <title>PE - Right Eye</title>
            <description>Phenylephrine 2.5% ophthalmic solution administered to the right eye with the Optejet microdose dispenser</description>
          </group>
          <group group_id="O6">
            <title>PE - Left Eye</title>
            <description>Phenylephrine 2.5% ophthalmic solution administered to the left eye with the Optejet microdose dispenser</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage 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 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 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="62"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="62"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="62"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="62"/>
                <count group_id="O5" value="62"/>
                <count group_id="O6" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.7"/>
                    <measurement group_id="O2" value="67.7"/>
                    <measurement group_id="O3" value="43.5"/>
                    <measurement group_id="O4" value="41.9"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" 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 subject'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>Tropicamide</title>
          <description>Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser</description>
        </group>
        <group group_id="E3">
          <title>Phenylephrine</title>
          <description>Phenylephrine 2.5% 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="62"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="62"/>
              </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="62"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="64"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Vital dye staining cornea present</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </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/NCT03751631
org study id: EYN-MYD-TP-31
nct id: NCT03751631
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/PE) vs. phenylephrine (PE) alone and tropicamide (TR) alone.
      Participants attended 3 visits. At each visit, after baseline measurements, 1 of the 3 drugs
      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 1 of the 3 study drugs was administered to both eyes (each participant's drug
      administration sequence was randomly determined). Afterwards, efficacy and safety assessments
      were performed at 20, 35, 50, 65, 80, 120, and 180 minutes.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This trial was a double-masked, active-controlled, cross-over superiority study evaluating the efficacy of the fixed combination drug vs. the drug's 2 individual components. All participants in the trial were to receive each of the 3 drugs.
primary purpose: Diagnostic
masking: Double (Participant, Outcomes Assessor)
masking description: There were no differences in the presentation of drug administered and all study personnel conducting ophthalmic assessments after drug 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: Percentage 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 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 participants. A higher percentage indicates a better outcome.
measure: Percentage 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 62 participants received each medication. Data is reported separately for the right and left eyes of the 62 participants. A higher percentage indicates a better outcome.
arm group label: 1-TR/PE, 2-TR, 3-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 study drug in each eye.
arm group label: 1-TR/PE, 2-PE, 3-TR
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 study drug in each eye.
arm group label: 1-TR, 2-TR/PE, 3-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 study drug in each eye.
arm group label: 1-TR, 2-PE, 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 study drug in each eye.
arm group label: 1-PE, 2-TR/PE, 3-TR
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 study drug in each eye.
arm group label: 1-PE, 2-TR, 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 study drug in each eye.
intervention type: Drug
intervention name: Tropicamide 1%-Phenylephrine 2.5% ophthalmic solution (TR/PE)
description: Fixed combination tropicamide 1%-phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
arm group label: 1-PE, 2-TR, 3-TR/PE
arm group label: 1-PE, 2-TR/PE, 3-TR
arm group label: 1-TR, 2-PE, 3-TR/PE
arm group label: 1-TR, 2-TR/PE, 3-PE
arm group label: 1-TR/PE, 2-PE, 3-TR
arm group label: 1-TR/PE, 2-TR, 3-PE
other name: Mydcombi
intervention type: Drug
intervention name: Tropicamide 1% ophthalmic solution (TR)
description: Tropicamide 1% ophthalmic solution administered with the Optejet microdose dispenser
arm group label: 1-PE, 2-TR, 3-TR/PE
arm group label: 1-PE, 2-TR/PE, 3-TR
arm group label: 1-TR, 2-PE, 3-TR/PE
arm group label: 1-TR, 2-TR/PE, 3-PE
arm group label: 1-TR/PE, 2-PE, 3-TR
arm group label: 1-TR/PE, 2-TR, 3-PE
intervention type: Drug
intervention name: Phenylephrine 2.5% ophthalmic solution (PE)
description: Phenylephrine 2.5% ophthalmic solution administered with the Optejet microdose dispenser
arm group label: 1-PE, 2-TR, 3-TR/PE
arm group label: 1-PE, 2-TR/PE, 3-TR
arm group label: 1-TR, 2-PE, 3-TR/PE
arm group label: 1-TR, 2-TR/PE, 3-PE
arm group label: 1-TR/PE, 2-PE, 3-TR
arm group label: 1-TR/PE, 2-TR, 3-PE
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: 
country: United States
responsible party type: Sponsor
mesh term: Mydriasis
mesh term: Phenylephrine
mesh term: Oxymetazoline
mesh term: Pharmaceutical Solutions
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: 