<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/NCT02184988</url>
  </required_header>
  <id_info>
    <org_study_id>Evolus - CLIN004</org_study_id>
    <nct_id>NCT02184988</nct_id>
  </id_info>
  <brief_title>Safety Study of DWP-450 (Botulinum Purified Neurotoxin, Type A) Injection to Treat Glabellar Lines</brief_title>
  <acronym>EV-004</acronym>
  <official_title>A Multi-center, Open Label, Multiple Dose, Phase II Trial to Demonstrate the Safety of DWP-450 in Adult Subjects for Treatment of Moderate-to-severe Glabellar Lines.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Evolus, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Evolus, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to demonstrate the safety of multiple doses of DWP-450&#xD;
      (Botulinum purified neurotoxin, Type A) Injection in treatment of moderate to severe&#xD;
      glabellar lines in adult subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Three hundred and fifty subjects will be enrolled and injected with the study drug DWP-450&#xD;
      over the course of the 365 day study.&#xD;
&#xD;
      Subjects with moderate or severe glabellar lines at maximum frown on the 4 point Glabellar&#xD;
      Line Scale (GLS, 0=none, 1= mild, 2=moderate, 3=severe), as judged by the investigator, will&#xD;
      be eligible for injection with DWP-450. After each injection, subjects will be followed and&#xD;
      are eligible for a repeat injection if their GLS is ≥2 at maximum frown, as judged by the&#xD;
      Investigator. If a subject does not have a GLS≥2 they will be followed monthly until eligible&#xD;
      for repeat treatment.&#xD;
&#xD;
      Subjects may receive up to a maximum of 4 treatments and will be followed for 365 days from&#xD;
      initial treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The Safety of Repeat DWP-450 Treatments - Proportion of Subjects With at Least One Adverse Event Over 1 Year</measure>
    <time_frame>365 Days</time_frame>
    <description>The primary safety analysis was the calculation of the proportion of subjects with at least one adverse event that occurred from Day 0 through Day 365.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Percentage of Subjects With an Improvement of 1 Point or More (i.e., ≥1 Point Responders) at Rest on Day 365, by Investigator Assessment on the Glabellar Line Scale (GLS)</measure>
    <time_frame>365 Days</time_frame>
    <description>GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe. A 1-point decrease in GLS score is equivalent to a 1-point improvement on the GLS; as such, both meet the definition of a 1-point responder on the GLS</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">352</enrollment>
  <condition>Glabellar Frown Lines</condition>
  <arm_group>
    <arm_group_label>Botulinum neurotoxin, Type A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DWP-450 (Botulinum purified neurotoxin, Type A) Injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Botulinum purified neurotoxin, Type A</intervention_name>
    <description>The subject is to be injected intra-muscularly into a total of five sites: the mid-line of the procures muscle, the inferomedial aspect of each corrugator muscle and the superior middle aspect of each corrugator, at least 1 cm above the bony orbital rim. Each site is injected with 0.1 ml (4U), for a total of 20 U and 0.5 ml.</description>
    <arm_group_label>Botulinum neurotoxin, Type A</arm_group_label>
    <other_name>DWP-450 (Botulinum purified neurotoxin, Type A) Injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (A subject must meet all of the following inclusion criteria in order to&#xD;
        be eligible for enrollment in the study):&#xD;
&#xD;
          -  Subjects must be an adult 18 years of age or over&#xD;
&#xD;
          -  Subject is able to provide informed consent and comply with study instructions&#xD;
&#xD;
          -  Subject has moderate to severe glabellar lines on maximum frown as assessed by the&#xD;
             investigator using the GLS&#xD;
&#xD;
          -  Subject is willing and able to complete the entire course of the study&#xD;
&#xD;
        Exclusion Criteria (A subject must not meet the following exclusion criteria in order to be&#xD;
        eligible for enrollment in the stud)y:&#xD;
&#xD;
          -  Previous treatment with botulinum toxin of any serotype in the forehead area within&#xD;
             the last 8 months&#xD;
&#xD;
          -  Previous treatment with any facial aesthetic procedure (e.g. injection with fillers,&#xD;
             chemical peeling, photo rejuvenation) in the glabellar area within the last 12 months&#xD;
&#xD;
          -  Previous insertion of permanent material in the glabellar area&#xD;
&#xD;
          -  Planned treatment with botulinum toxin of any serotype in any other body region during&#xD;
             the study period&#xD;
&#xD;
          -  Any surgery in the glabellar area including surgical removal of the corrugator,&#xD;
             procerus, or depressor supercilii muscles or a combination of these, or scars in the&#xD;
             glabellar area and the surrounding areas (including eye brow)&#xD;
&#xD;
          -  Energy based or cryo-therapy based treatment of facial muscles superior to the lateral&#xD;
             canthus&#xD;
&#xD;
          -  Any other planned facial aesthetic procedure during the trial period, superior to the&#xD;
             level of the lateral canthus (subjects can continue with their usual skin care&#xD;
             routine)&#xD;
&#xD;
          -  Inability to substantially lessen glabellar frown lines even by physically spreading&#xD;
             them apart&#xD;
&#xD;
          -  Marked facial asymmetry&#xD;
&#xD;
          -  Ptosis of eyelid and/or eyebrow, or history of eyelid and/or eyebrow ptosis&#xD;
&#xD;
          -  History of facial nerve palsy&#xD;
&#xD;
          -  Excessive dermatochalasis, deep dermal scarring, thick sebaceous skin&#xD;
&#xD;
          -  Any active infection in the area of the injection sites&#xD;
&#xD;
          -  Medical condition that may affect neuromuscular function (e.g., myasthenia gravis,&#xD;
             Eaton-Lambert syndrome, amyotrophic lateral sclerosis)&#xD;
&#xD;
          -  Evidence of recent alcohol or drug abuse&#xD;
&#xD;
          -  Medical or psychiatric conditions that may increase the risk associated with study&#xD;
             participation or may interfere with the interpretation of study results and, in the&#xD;
             judgment of the Investigator, would make the subject inappropriate for entry into this&#xD;
             study&#xD;
&#xD;
          -  Pregnant or sexually active female subjects who are of childbearing potential and who&#xD;
             are not willing to use an acceptable form of contraception&#xD;
&#xD;
          -  Known allergy or hypersensitivity to botulinum toxin preparation&#xD;
&#xD;
          -  Participation in another interventional clinical study within the last 30 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rui Avelar, MD</last_name>
    <role>Study Director</role>
    <affiliation>Evolus, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ATS Clinical Research</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>July 2, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <results_first_submitted>January 11, 2019</results_first_submitted>
  <results_first_submitted_qc>January 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">February 5, 2019</results_first_posted>
  <disposition_first_submitted>February 1, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>March 20, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 21, 2017</disposition_first_posted>
  <last_update_submitted>April 22, 2019</last_update_submitted>
  <last_update_submitted_qc>April 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glabellar Lines</keyword>
  <keyword>Botulinum purifies neurotoxin, Type A (DWP-450)</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Analysis will be of combined data for all subjects entered into the study</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Botulinum Neurotoxin, Type A</title>
          <description>DWP-450 (Botulinum purified neurotoxin, Type A) Injection&#xD;
Botulinum purified neurotoxin, Type A: The subject is to be injected intra-muscularly into a total of five sites: the mid-line of the procures muscle, the inferomedial aspect of each corrugator muscle and the superior middle aspect of each corrugator, at least 1 cm above the bony orbital rim. Each site is injected with 0.1 ml (4U), for a total of 20 U and 0.5 ml.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="352"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="297"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="55"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>moving away/travelling/unable to complet</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>work scheduling issues</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>various other reasons</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Botulinum Neurotoxin, Type A</title>
          <description>DWP-450 (Botulinum purified neurotoxin, Type A) Injection&#xD;
Botulinum purified neurotoxin, Type A: The subject is to be injected intra-muscularly into a total of five sites: the mid-line of the procures muscle, the inferomedial aspect of each corrugator muscle and the superior middle aspect of each corrugator, at least 1 cm above the bony orbital rim. Each site is injected with 0.1 ml (4U), for a total of 20 U and 0.5 ml.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="352"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="319"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </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="331"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Safety of Repeat DWP-450 Treatments - Proportion of Subjects With at Least One Adverse Event Over 1 Year</title>
        <description>The primary safety analysis was the calculation of the proportion of subjects with at least one adverse event that occurred from Day 0 through Day 365.</description>
        <time_frame>365 Days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Neurotoxin, Type A</title>
            <description>DWP-450 (Botulinum purified neurotoxin, Type A) Injection&#xD;
Botulinum purified neurotoxin, Type A: The subject is to be injected intra-muscularly into a total of five sites: the mid-line of the procures muscle, the inferomedial aspect of each corrugator muscle and the superior middle aspect of each corrugator, at least 1 cm above the bony orbital rim. Each site is injected with 0.1 ml (4U), for a total of 20 U and 0.5 ml.</description>
          </group>
        </group_list>
        <measure>
          <title>The Safety of Repeat DWP-450 Treatments - Proportion of Subjects With at Least One Adverse Event Over 1 Year</title>
          <description>The primary safety analysis was the calculation of the proportion of subjects with at least one adverse event that occurred from Day 0 through Day 365.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="352"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage of Subjects With an Improvement of 1 Point or More (i.e., ≥1 Point Responders) at Rest on Day 365, by Investigator Assessment on the Glabellar Line Scale (GLS)</title>
        <description>GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe. A 1-point decrease in GLS score is equivalent to a 1-point improvement on the GLS; as such, both meet the definition of a 1-point responder on the GLS</description>
        <time_frame>365 Days</time_frame>
        <population>323 subjects had a GLS score at rest &gt;0 (i.e., 1, 2 or 3) at baseline and therefore could potentially have had a ≥1 point improvement in GLS score at rest at a post-baseline visit; 32 were missing the EOS GLS assessment</population>
        <group_list>
          <group group_id="O1">
            <title>Botulinum Neurotoxin, Type A</title>
            <description>DWP-450 (Botulinum purified neurotoxin, Type A) Injection&#xD;
Botulinum purified neurotoxin, Type A: The subject is to be injected intra-muscularly into a total of five sites: the mid-line of the procures muscle, the inferomedial aspect of each corrugator muscle and the superior middle aspect of each corrugator, at least 1 cm above the bony orbital rim. Each site is injected with 0.1 ml (4U), for a total of 20 U and 0.5 ml.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With an Improvement of 1 Point or More (i.e., ≥1 Point Responders) at Rest on Day 365, by Investigator Assessment on the Glabellar Line Scale (GLS)</title>
          <description>GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe. A 1-point decrease in GLS score is equivalent to a 1-point improvement on the GLS; as such, both meet the definition of a 1-point responder on the GLS</description>
          <population>323 subjects had a GLS score at rest &gt;0 (i.e., 1, 2 or 3) at baseline and therefore could potentially have had a ≥1 point improvement in GLS score at rest at a post-baseline visit; 32 were missing the EOS GLS assessment</population>
          <units>percentage of responders</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="291"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.9" lower_limit="70.6" upper_limit="80.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Botulinum Neurotoxin, Type A</title>
          <description>DWP-450 (Botulinum purified neurotoxin, Type A) Injection&#xD;
Botulinum purified neurotoxin, Type A: The subject is to be injected intra-muscularly into a total of five sites: the mid-line of the procures muscle, the inferomedial aspect of each corrugator muscle and the superior middle aspect of each corrugator, at least 1 cm above the bony orbital rim. Each site is injected with 0.1 ml (4U), for a total of 20 U and 0.5 ml.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Device failure - failure of pacemaker/defibrillator</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Malignant anorectal neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Ovarian Adenoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Dysfunctional uterine bleeding</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="141" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>atrial tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>palpitations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>ear congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenopia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Eyelid edema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Eyelid ptosis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Presbyopia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>gastro-esophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>large intestine polyp</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>pancreatic cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>pancreatic pseudocyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>injection site cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>injection site laceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>injury associated with a device</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>seasonal allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>abscess limb</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>cystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>ear infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>herpes zoster</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>laryngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>oral candidiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>oral herpes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>pharyngitis streptococcal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>tinea faciei</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Meniscus injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>arthropod bite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>incision site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>limb injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>lip injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>median nerve injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>post procedural swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>road traffic accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>thermal burn</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>wrist fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>glucose in urine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>hypercholesterolemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>hyperlipidemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>bursitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>osteoarthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>osteoporosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>pain in jaw</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>rheumatoid arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>tendonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>tenosynovitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Melanocytic nevus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>benign breast neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>ovarian adenoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="65" subjects_affected="54" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Muscle tone disorder</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Sinus headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Speech disorder</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Migraine with aura</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Nerve compression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Post herpetic neuralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Thoracic outlet syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>ADHD</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>nephrolithiasis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>vulvovaginal swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>Endometrial Hyperplasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>sinus congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermal cyst</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>acne</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>dermatitis contact</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>ecchymosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>psoriasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>rosacea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>skin tightening</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
              <event>
                <sub_title>skin wrinkling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="352"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>hypertension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="352"/>
              </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>Rui L. Avelar, MD</name_or_title>
      <organization>Evolus, Inc</organization>
      <phone>(805)689-8668</phone>
      <email>rui@evolusinc.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/NCT02184988
org study id: Evolus - CLIN004
nct id: NCT02184988
lead sponsor: 
has dmc: No
The purpose of this study is to demonstrate the safety of multiple doses of DWP-450
      (Botulinum purified neurotoxin, Type A) Injection in treatment of moderate to severe
      glabellar lines in adult subjects.
Three hundred and fifty subjects will be enrolled and injected with the study drug DWP-450
      over the course of the 365 day study.

      Subjects with moderate or severe glabellar lines at maximum frown on the 4 point Glabellar
      Line Scale (GLS, 0=none, 1= mild, 2=moderate, 3=severe), as judged by the investigator, will
      be eligible for injection with DWP-450. After each injection, subjects will be followed and
      are eligible for a repeat injection if their GLS is ≥2 at maximum frown, as judged by the
      Investigator. If a subject does not have a GLS≥2 they will be followed monthly until eligible
      for repeat treatment.

      Subjects may receive up to a maximum of 4 treatments and will be followed for 365 days from
      initial treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: The Safety of Repeat DWP-450 Treatments - Proportion of Subjects With at Least One Adverse Event Over 1 Year
time frame: 365 Days
description: The primary safety analysis was the calculation of the proportion of subjects with at least one adverse event that occurred from Day 0 through Day 365.
measure: Percentage of Subjects With an Improvement of 1 Point or More (i.e., ≥1 Point Responders) at Rest on Day 365, by Investigator Assessment on the Glabellar Line Scale (GLS)
time frame: 365 Days
description: GLS is scored: 0=none, 1=mild, 2=moderate, 3=severe. A 1-point decrease in GLS score is equivalent to a 1-point improvement on the GLS; as such, both meet the definition of a 1-point responder on the GLS
arm group label: Botulinum neurotoxin, Type A
arm group type: Experimental
description: DWP-450 (Botulinum purified neurotoxin, Type A) Injection
intervention type: Biological
intervention name: Botulinum purified neurotoxin, Type A
description: The subject is to be injected intra-muscularly into a total of five sites: the mid-line of the procures muscle, the inferomedial aspect of each corrugator muscle and the superior middle aspect of each corrugator, at least 1 cm above the bony orbital rim. Each site is injected with 0.1 ml (4U), for a total of 20 U and 0.5 ml.
arm group label: Botulinum neurotoxin, Type A
other name: DWP-450 (Botulinum purified neurotoxin, Type A) Injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Rui Avelar, MD
role: Study Director
affiliation: Evolus, Inc.
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No
ipd description: Analysis will be of combined data for all subjects entered into the study
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 