<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/NCT03839693</url>
  </required_header>
  <id_info>
    <org_study_id>ET-01-LCL-208</org_study_id>
    <nct_id>NCT03839693</nct_id>
  </id_info>
  <brief_title>ET-01 in Subjects With Lateral Canthal Lines, LCL-208</brief_title>
  <official_title>Clinical Trial to Evaluate ET-01 in Subjects With Lateral Canthal Lines</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eirion Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eirion Therapeutics Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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 tests an investigational drug formulation called ET-01, botulinum toxin, Type A,&#xD;
      topical, in lateral canthal lines (LCL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This product is being tested for its ability to reduce lateral canthal lines, also known as&#xD;
      Crow's Feet.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2018</start_date>
  <completion_date type="Actual">September 19, 2019</completion_date>
  <primary_completion_date type="Actual">April 18, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>sequential cohort, dose escalating study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With a Response Defined as Change in IGA-C (Investigators Global Assessment) Score by at Least 2 Ordinals From Baseline to Week 4</measure>
    <time_frame>Week 4</time_frame>
    <description>Investigators Global Assessment of the Crow's Feet Wrinkle Scale where severity is scored between 0-4 (0=absent; 4=severe). Response is defined as change by at least two ordinals from Baseline to Week 4.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Number of Observations With a Response Defined as Change ≥2 in IGA-C and SSA-C Score at Any Post Baseline Visit</measure>
    <time_frame>Week 1, 2, 4, 8,12,18, and 26</time_frame>
    <description>Total number of observations with a change in the Investigators Global Assessment on Contraction, IGA-C, and the Subject Self-Assessment on Contraction, SSA-C, using the Crow's Feet Wrinkle Scale, where severity is scored between 0-4 (0=absent; 4=severe). To count, a &quot;responder&quot; is defined as a change by at least two ordinals in both assessments. The observation period includes all post-baseline visits from Week 1 to Week 26.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of Observations With a Response Defined as Change in SSA-C Score ≥ 2 at Any Time Between Week 4 and Week 12</measure>
    <time_frame>Week 4, 8,and 12</time_frame>
    <description>Total number of observations with a change by at least two ordinals in the Subjects Self-Assessment on Contraction, SSA-C, using the Crow's Feet Wrinkle Scale, where severity is scored between 0-4 (0=absent; 4=severe). To count, a &quot;responder&quot; is defined as an improvement ≥ 2 score points. The observation period covers the time time of expected peak efficacy from Week 4 to Week 12.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Lateral Canthal Lines</condition>
  <condition>Crow's Feet</condition>
  <arm_group>
    <arm_group_label>Vehicle</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vehicle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ET-01 345U</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>botulinum toxin, Type A, Dose 1, 345 U</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ET-01 1100U</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>botulinum toxin, Type A, Dose 2, 1100 U</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>botulinum toxin, Type A</intervention_name>
    <description>topical liniment</description>
    <arm_group_label>ET-01 1100U</arm_group_label>
    <arm_group_label>ET-01 345U</arm_group_label>
    <other_name>ET-01</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Vehicle</intervention_name>
    <description>Vehicle Formulation</description>
    <arm_group_label>Vehicle</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  females 25 - 65 years of age&#xD;
&#xD;
          -  minimal to moderate Crow's Feet wrinkles at rest&#xD;
&#xD;
          -  moderate to severe Crow's Feet on contraction&#xD;
&#xD;
          -  adequate vision to assess facial wrinkles in a mirror&#xD;
&#xD;
          -  willingness to refrain from products affecting skin remodeling&#xD;
&#xD;
          -  female subjects must be not pregnant and non-lactating&#xD;
&#xD;
          -  subjects should be in good general health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  history of adverse reactions to any prior botulinum toxin treatments&#xD;
&#xD;
          -  history of vaccination or non-response to any prior botulinum toxin treatments&#xD;
&#xD;
          -  botulinum toxin treatment in the prior 6 months&#xD;
&#xD;
          -  present or history of neuromuscular disease, eyelid ptosis, muscle weakness,&#xD;
             paralysis, or &quot;dry eye&quot;&#xD;
&#xD;
          -  history of peri-ocular surgery, brow lift or related procedures&#xD;
&#xD;
          -  procedures affecting the lateral canthal region in the prior 12 months&#xD;
&#xD;
          -  application of topical prescription medication to the treatment area&#xD;
&#xD;
          -  female subjects who are pregnant or are nursing a child&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Baumann Cosmetic &amp; Research Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33137</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus, Inc.</name>
      <address>
        <city>Pinellas Park</city>
        <state>Florida</state>
        <zip>33781</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Forefront Dermatology</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westlake Dermatology Clinical Research Center</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78746</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Clinical Research, Inc.</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>February 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <results_first_submitted>May 20, 2022</results_first_submitted>
  <results_first_submitted_qc>June 30, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 26, 2022</results_first_posted>
  <disposition_first_submitted>May 20, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>June 30, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">July 26, 2022</disposition_first_posted>
  <last_update_submitted>July 27, 2022</last_update_submitted>
  <last_update_submitted_qc>July 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins</mesh_term>
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT03839693/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from five medical centers between October 2018 and March 2019.</recruitment_details>
      <pre_assignment_details>A total of N=88 subjects were screened; N=75 were found eligible and were randomized and treated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Vehicle</title>
          <description>Vehicle&#xD;
Vehicle: Vehicle Formulation</description>
        </group>
        <group group_id="P2">
          <title>ET-01 345U</title>
          <description>botulinum toxin, Type A, Dose 1, 345U&#xD;
lower dose of botulinum toxin, Type A: topical liniment</description>
        </group>
        <group group_id="P3">
          <title>ET-01 1100U</title>
          <description>botulinum toxin, Type A, Dose 2, 1100U&#xD;
higher dose of botulinum toxin, Type A: topical liniment</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="30"/>
                <participants group_id="P3" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>subject moved out of the area</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vehicle</title>
          <description>Vehicle&#xD;
Vehicle: Vehicle Formulation</description>
        </group>
        <group group_id="B2">
          <title>ET-01 345U</title>
          <description>botulinum toxin, Type A, Lower Dose 1, 345U&#xD;
botulinum toxin, Type A: topical liniment</description>
        </group>
        <group group_id="B3">
          <title>ET-01 1100U</title>
          <description>botulinum toxin, Type A, Higher Dose 2, 1100U&#xD;
botulinum toxin, Type A: topical liniment</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="20"/>
            <count group_id="B4" value="75"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="71"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </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="25"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="20"/>
                    <measurement group_id="B4" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="61"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>IGA-C</title>
          <description>Investigator Global Assessment on Contraction using the ordinal Crow's Feet Wrinkle Scale where severity is scored between 0=absent and 4=severe.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.3" spread="0.4"/>
                    <measurement group_id="B2" value="3.5" spread="0.5"/>
                    <measurement group_id="B3" value="3.5" spread="0.5"/>
                    <measurement group_id="B4" value="3.4" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>SSA-C</title>
          <description>Subject Self-Assessment. Crow's Feet Wrinkle Scale where severity is scored between 0-4 (0=absent; 4=severe).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.5" spread="0.5"/>
                    <measurement group_id="B2" value="3.7" spread="0.5"/>
                    <measurement group_id="B3" value="3.8" spread="0.4"/>
                    <measurement group_id="B4" value="3.6" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With a Response Defined as Change in IGA-C (Investigators Global Assessment) Score by at Least 2 Ordinals From Baseline to Week 4</title>
        <description>Investigators Global Assessment of the Crow's Feet Wrinkle Scale where severity is scored between 0-4 (0=absent; 4=severe). Response is defined as change by at least two ordinals from Baseline to Week 4.</description>
        <time_frame>Week 4</time_frame>
        <population>Intent-To-Treat (ITT) population defined as all treated subjects who had at least one post-baseline visit. No imputation was performed when only incomplete data were available.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Vehicle&#xD;
Vehicle: Vehicle Formulation</description>
          </group>
          <group group_id="O2">
            <title>ET-01 345U</title>
            <description>botulinum toxin, Type A, Dose 1&#xD;
botulinum toxin, Type A: topical liniment</description>
          </group>
          <group group_id="O3">
            <title>ET-01 1100U</title>
            <description>botulinum toxin, Type A, Dose 2&#xD;
botulinum toxin, Type A: topical liniment</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Response Defined as Change in IGA-C (Investigators Global Assessment) Score by at Least 2 Ordinals From Baseline to Week 4</title>
          <description>Investigators Global Assessment of the Crow's Feet Wrinkle Scale where severity is scored between 0-4 (0=absent; 4=severe). Response is defined as change by at least two ordinals from Baseline to Week 4.</description>
          <population>Intent-To-Treat (ITT) population defined as all treated subjects who had at least one post-baseline visit. No imputation was performed when only incomplete data were available.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="30"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of Observations With a Response Defined as Change ≥2 in IGA-C and SSA-C Score at Any Post Baseline Visit</title>
        <description>Total number of observations with a change in the Investigators Global Assessment on Contraction, IGA-C, and the Subject Self-Assessment on Contraction, SSA-C, using the Crow's Feet Wrinkle Scale, where severity is scored between 0-4 (0=absent; 4=severe). To count, a &quot;responder&quot; is defined as a change by at least two ordinals in both assessments. The observation period includes all post-baseline visits from Week 1 to Week 26.</description>
        <time_frame>Week 1, 2, 4, 8,12,18, and 26</time_frame>
        <population>Intent-To-Treat (ITT) population defined as all treated subjects who had at least one post-baseline visit. No imputation was performed when only incomplete data were available.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Vehicle&#xD;
Vehicle: Vehicle Formulation</description>
          </group>
          <group group_id="O2">
            <title>ET-01 345U</title>
            <description>botulinum toxin, Type A, Dose 1&#xD;
botulinum toxin, Type A: topical liniment</description>
          </group>
          <group group_id="O3">
            <title>ET-01 1100U</title>
            <description>botulinum toxin, Type A, Dose 2&#xD;
botulinum toxin, Type A: topical liniment</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Observations With a Response Defined as Change ≥2 in IGA-C and SSA-C Score at Any Post Baseline Visit</title>
          <description>Total number of observations with a change in the Investigators Global Assessment on Contraction, IGA-C, and the Subject Self-Assessment on Contraction, SSA-C, using the Crow's Feet Wrinkle Scale, where severity is scored between 0-4 (0=absent; 4=severe). To count, a &quot;responder&quot; is defined as a change by at least two ordinals in both assessments. The observation period includes all post-baseline visits from Week 1 to Week 26.</description>
          <population>Intent-To-Treat (ITT) population defined as all treated subjects who had at least one post-baseline visit. No imputation was performed when only incomplete data were available.</population>
          <units>Observations</units>
          <param>Count of Units</param>
          <units_analyzed>Observations</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="30"/>
                <count group_id="O3" value="20"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Observations</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="162"/>
                <count group_id="O2" value="202"/>
                <count group_id="O3" value="131"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of Observations With a Response Defined as Change in SSA-C Score ≥ 2 at Any Time Between Week 4 and Week 12</title>
        <description>Total number of observations with a change by at least two ordinals in the Subjects Self-Assessment on Contraction, SSA-C, using the Crow's Feet Wrinkle Scale, where severity is scored between 0-4 (0=absent; 4=severe). To count, a &quot;responder&quot; is defined as an improvement ≥ 2 score points. The observation period covers the time time of expected peak efficacy from Week 4 to Week 12.</description>
        <time_frame>Week 4, 8,and 12</time_frame>
        <population>Intent-To-Treat (ITT) population defined as all treated subjects who had at least one post-baseline visit. No imputation was performed when only incomplete data were available.</population>
        <group_list>
          <group group_id="O1">
            <title>Vehicle</title>
            <description>Vehicle&#xD;
Vehicle: Vehicle Formulation</description>
          </group>
          <group group_id="O2">
            <title>ET-01 345U</title>
            <description>botulinum toxin, Type A, Lower Dose 1&#xD;
botulinum toxin, Type A: topical liniment</description>
          </group>
          <group group_id="O3">
            <title>ET-01 1100U</title>
            <description>botulinum toxin, Type A, Higher Dose 2&#xD;
botulinum toxin, Type A: topical liniment</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Observations With a Response Defined as Change in SSA-C Score ≥ 2 at Any Time Between Week 4 and Week 12</title>
          <description>Total number of observations with a change by at least two ordinals in the Subjects Self-Assessment on Contraction, SSA-C, using the Crow's Feet Wrinkle Scale, where severity is scored between 0-4 (0=absent; 4=severe). To count, a &quot;responder&quot; is defined as an improvement ≥ 2 score points. The observation period covers the time time of expected peak efficacy from Week 4 to Week 12.</description>
          <population>Intent-To-Treat (ITT) population defined as all treated subjects who had at least one post-baseline visit. No imputation was performed when only incomplete data were available.</population>
          <units>Observations</units>
          <param>Count of Units</param>
          <units_analyzed>Observations</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="30"/>
                <count group_id="O3" value="19"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Observations</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>26 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Vehicle</title>
          <description>Vehicle&#xD;
Vehicle: Vehicle Formulation</description>
        </group>
        <group group_id="E2">
          <title>ET-01 345U</title>
          <description>botulinum toxin, Type A, Lower Dose 1, 345U&#xD;
botulinum toxin, Type A: topical liniment</description>
        </group>
        <group group_id="E3">
          <title>ET-01 1100U</title>
          <description>botulinum toxin, Type A, Higher Dose 2, 1100U&#xD;
botulinum toxin, Type A: topical liniment</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="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
              </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="13" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Thyroiditis subacute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Endometrial ablation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Application site pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nail dystrophy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Skin discolouration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Endodontic procedure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Mammoplasty</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Study Results are considered Confidential Information that may not be published or disclosed without Sponsor's written consent for a period of five (5) years after completion of the Study.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Patrick Murphy</name_or_title>
      <organization>Clinical Research Management Group</organization>
      <phone>4138210022</phone>
      <email>p.murphy@crmg-usa.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/NCT03839693
org study id: ET-01-LCL-208
nct id: NCT03839693
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study tests an investigational drug formulation called ET-01, botulinum toxin, Type A,
      topical, in lateral canthal lines (LCL).
This product is being tested for its ability to reduce lateral canthal lines, also known as
      Crow's Feet.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: sequential cohort, dose escalating study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants With a Response Defined as Change in IGA-C (Investigators Global Assessment) Score by at Least 2 Ordinals From Baseline to Week 4
time frame: Week 4
description: Investigators Global Assessment of the Crow's Feet Wrinkle Scale where severity is scored between 0-4 (0=absent; 4=severe). Response is defined as change by at least two ordinals from Baseline to Week 4.
measure: Total Number of Observations With a Response Defined as Change ≥2 in IGA-C and SSA-C Score at Any Post Baseline Visit
time frame: Week 1, 2, 4, 8,12,18, and 26
description: Total number of observations with a change in the Investigators Global Assessment on Contraction, IGA-C, and the Subject Self-Assessment on Contraction, SSA-C, using the Crow's Feet Wrinkle Scale, where severity is scored between 0-4 (0=absent; 4=severe). To count, a "responder" is defined as a change by at least two ordinals in both assessments. The observation period includes all post-baseline visits from Week 1 to Week 26.
measure: Total Number of Observations With a Response Defined as Change in SSA-C Score ≥ 2 at Any Time Between Week 4 and Week 12
time frame: Week 4, 8,and 12
description: Total number of observations with a change by at least two ordinals in the Subjects Self-Assessment on Contraction, SSA-C, using the Crow's Feet Wrinkle Scale, where severity is scored between 0-4 (0=absent; 4=severe). To count, a "responder" is defined as an improvement ≥ 2 score points. The observation period covers the time time of expected peak efficacy from Week 4 to Week 12.
arm group label: Vehicle
arm group type: Placebo Comparator
description: Vehicle
arm group label: ET-01 345U
arm group type: Experimental
description: botulinum toxin, Type A, Dose 1, 345 U
arm group label: ET-01 1100U
arm group type: Experimental
description: botulinum toxin, Type A, Dose 2, 1100 U
intervention type: Biological
intervention name: botulinum toxin, Type A
description: topical liniment
arm group label: ET-01 1100U
arm group label: ET-01 345U
other name: ET-01
intervention type: Biological
intervention name: Vehicle
description: Vehicle Formulation
arm group label: Vehicle
criteria: 
gender: Female
minimum age: 25 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 