<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/NCT02261493</url>
  </required_header>
  <id_info>
    <org_study_id>191622-143</org_study_id>
    <secondary_id>2014-001815-38</secondary_id>
    <nct_id>NCT02261493</nct_id>
  </id_info>
  <brief_title>A Safety and Efficacy Study of OnabotulinumtoxinA in Upper Facial Rhytides</brief_title>
  <official_title>Evaluation of the Safety and Efficacy of Treatment With BOTOX® (Botulinum Toxin Type A) Purified Neurotoxin Complex for Subjects With Facial Rhytides (Forehead Lines, Glabellar Lines, Lateral Canthal Lines)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Allergan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a safety and efficacy study of onabotulinumtoxinA in subjects with upper facial&#xD;
      rhytides (forehead lines, glabellar lines, lateral canthal lines [crow's feet lines]).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 27, 2014</start_date>
  <completion_date type="Actual">April 20, 2016</completion_date>
  <primary_completion_date type="Actual">June 3, 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation</measure>
    <time_frame>Baseline, Day 30</time_frame>
    <description>The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation</measure>
    <time_frame>Day 30</time_frame>
    <description>The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of &quot;none&quot; and &quot;mild&quot; are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest</measure>
    <time_frame>Baseline, Day 30</time_frame>
    <description>The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5</measure>
    <time_frame>Day 60</time_frame>
    <description>The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks &quot;How satisfied are you with the effect your treatment had on your facial lines?&quot; Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points</measure>
    <time_frame>Baseline, Day 30</time_frame>
    <description>The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire©</measure>
    <time_frame>Baseline, Day 30</time_frame>
    <description>The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is &quot;I look older than my actual age because of my facial lines&quot; with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Retreatment Eligibility</measure>
    <time_frame>12 Months</time_frame>
    <description>Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">787</enrollment>
  <condition>Facial Rhytides</condition>
  <condition>Glabellar Rhytides</condition>
  <arm_group>
    <arm_group_label>OnabotulinumtoxinA Dose A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OnabotulinumtoxinA Dose B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo followed by OnabotulinumtoxinA Dose A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>OnabotulinumtoxinA</intervention_name>
    <description>OnabotulinumtoxinA injected into the protocol-specified areas. Subjects will receive at least 1 and up to 3 treatments.</description>
    <arm_group_label>OnabotulinumtoxinA Dose A</arm_group_label>
    <arm_group_label>OnabotulinumtoxinA Dose B</arm_group_label>
    <other_name>BOTOX® Cosmetic</other_name>
    <other_name>botulinum toxin Type A</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline</intervention_name>
    <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1.</description>
    <arm_group_label>Placebo followed by OnabotulinumtoxinA Dose A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Moderate to severe forehead lines, glabellar lines, and crow's feet lines&#xD;
&#xD;
          -  Willing to have facial photos taken&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior exposure to botulinum toxin of any serotype for any indication&#xD;
&#xD;
          -  Anticipated need for treatment with botulinum toxin of any serotype for any indication&#xD;
             during the study, other than study treatment&#xD;
&#xD;
          -  Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral&#xD;
             sclerosis&#xD;
&#xD;
          -  Any facial resurfacing laser or light treatment, microdermabrasion, or superficial&#xD;
             peels in the past 3 months&#xD;
&#xD;
          -  Any medium depth or deep depth facial chemical peels; facial skin resurfacing; or&#xD;
             permanent facial make-up in the past 6 months&#xD;
&#xD;
          -  Any nonpermanent soft tissue fillers, or treatment with oral retinoids in the past&#xD;
             year - Prior face lift, thread lift, eyebrow lift, or related procedures (eg, eyelid&#xD;
             and/or eyebrow surgery)&#xD;
&#xD;
          -  Prior facial treatment with permanent soft tissue fillers, synthetic implants (eg,&#xD;
             Gore-Tex®), and/or fat transplantation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Allergan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Petrus Center for Aesthetic</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westside Aesthetics</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Research Foundation</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Steve Yoelin, MD Medical Associates, Inc.</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>Saint Louis University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center For Dermatology Cosmetic and Laser Surgery</name>
      <address>
        <city>Mount Kisco</city>
        <state>New York</state>
        <zip>10549</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Clinical Research Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Skin Research</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Premier Clinical Research</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aalst Dermatology Clinic</name>
      <address>
        <city>Aalst</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Brussel</name>
      <address>
        <city>Jette</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Skin Care - Sint-Truiden</name>
      <address>
        <city>Limburg</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rosenpark Research</name>
      <address>
        <city>Darmstadt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hautzentrum Koeln (Cologne Dermatology)</name>
      <address>
        <city>Köln Nordrhein-Westfalen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hautok und hautok-cosmetics</name>
      <address>
        <city>München</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxisgemeinschaft Theatiner46</name>
      <address>
        <city>München</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hautzentrum am Starnberger See GmbH</name>
      <address>
        <city>Starnberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CentroDerm Study Center</name>
      <address>
        <city>Wuppertal</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shakespeare House Health Centre, General Practice</name>
      <address>
        <city>Basingstoke</city>
        <zip>RG24 9DT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizen Clinic</name>
      <address>
        <city>Birmingham</city>
        <zip>B74 2UG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Bosham Clinic</name>
      <address>
        <city>Chichester</city>
        <zip>PO18 8AN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waverlery Medical Practice</name>
      <address>
        <city>Coatbridge</city>
        <zip>ML5 3PA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Gatehouse</name>
      <address>
        <city>Whitegate</city>
        <zip>CW9 8UW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <results_first_submitted>June 26, 2017</results_first_submitted>
  <results_first_submitted_qc>June 26, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 25, 2017</results_first_posted>
  <disposition_first_submitted>June 3, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>June 3, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">June 7, 2016</disposition_first_posted>
  <last_update_submitted>June 26, 2017</last_update_submitted>
  <last_update_submitted_qc>June 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Facies</mesh_term>
  </condition_browse>
  <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>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Subjects were randomized to placebo, onabotulinumtoxinA Dose A, or onabotulinumtoxinA Dose B in Period 1. Subjects randomized to receive placebo or Dose B in Period 1, who subsequently continued to Period 2, received onabotulinumtoxinA Dose A in Period 2.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
          <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
        </group>
        <group group_id="P2">
          <title>OnabotulinumtoxinA Dose B</title>
          <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
        </group>
        <group group_id="P3">
          <title>OnabotulinumtoxinA Dose A</title>
          <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="156"/>
                <participants group_id="P2" count="318"/>
                <participants group_id="P3" count="313"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="271"/>
                <participants group_id="P3" count="287"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="47"/>
                <participants group_id="P3" count="26"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Noncompliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Undisclosed alcohol abuse</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</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>
              <title>Personal Reasons</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="27"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <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>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
          <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
        </group>
        <group group_id="B2">
          <title>OnabotulinumtoxinA Dose B</title>
          <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
        </group>
        <group group_id="B3">
          <title>OnabotulinumtoxinA Dose A</title>
          <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</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="156"/>
            <count group_id="B2" value="318"/>
            <count group_id="B3" value="313"/>
            <count group_id="B4" value="787"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt;65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="147"/>
                    <measurement group_id="B2" value="300"/>
                    <measurement group_id="B3" value="302"/>
                    <measurement group_id="B4" value="749"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="38"/>
                  </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="140"/>
                    <measurement group_id="B2" value="278"/>
                    <measurement group_id="B3" value="284"/>
                    <measurement group_id="B4" value="702"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="29"/>
                    <measurement group_id="B4" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation</title>
        <description>The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported.</description>
        <time_frame>Baseline, Day 30</time_frame>
        <population>Intent-to-Treat: all randomized subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
            <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA Dose B</title>
            <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
          <group group_id="O3">
            <title>OnabotulinumtoxinA Dose A</title>
            <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation</title>
          <description>The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported.</description>
          <population>Intent-to-Treat: all randomized subjects</population>
          <units>Percentage of Subjects</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="156"/>
                <count group_id="O2" value="318"/>
                <count group_id="O3" value="313"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" lower_limit="-0.6" upper_limit="1.9"/>
                    <measurement group_id="O2" value="45.6" lower_limit="40.1" upper_limit="51.1"/>
                    <measurement group_id="O3" value="53.0" lower_limit="47.5" upper_limit="58.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation</title>
        <description>The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of &quot;none&quot; and &quot;mild&quot; are reported.</description>
        <time_frame>Day 30</time_frame>
        <population>Intent-to-Treat: all randomized subjects with a score of &quot;none&quot; and &quot;mild&quot; on the FWS at maximum eyebrow elevation</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
            <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA Dose B</title>
            <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
          <group group_id="O3">
            <title>OnabotulinumtoxinA Dose A</title>
            <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation</title>
          <description>The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of &quot;none&quot; and &quot;mild&quot; are reported.</description>
          <population>Intent-to-Treat: all randomized subjects with a score of &quot;none&quot; and &quot;mild&quot; on the FWS at maximum eyebrow elevation</population>
          <units>Percentage of Subjects</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="156"/>
                <count group_id="O2" value="318"/>
                <count group_id="O3" value="313"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" lower_limit="0.8" upper_limit="6.9"/>
                    <measurement group_id="O2" value="90.3" lower_limit="87.0" upper_limit="93.5"/>
                    <measurement group_id="O3" value="94.9" lower_limit="92.4" upper_limit="97.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest</title>
        <description>The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported.</description>
        <time_frame>Baseline, Day 30</time_frame>
        <population>Intent-to-Treat: all randomized subjects with at least a 1-grade improvement assessed by the Investigator on the FWS at rest</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
            <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA Dose B</title>
            <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
          <group group_id="O3">
            <title>OnabotulinumtoxinA Dose A</title>
            <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest</title>
          <description>The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported.</description>
          <population>Intent-to-Treat: all randomized subjects with at least a 1-grade improvement assessed by the Investigator on the FWS at rest</population>
          <units>Percentage of Subjects</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="150"/>
                <count group_id="O2" value="310"/>
                <count group_id="O3" value="309"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.7" lower_limit="12.4" upper_limit="24.9"/>
                    <measurement group_id="O2" value="85.2" lower_limit="81.2" upper_limit="89.1"/>
                    <measurement group_id="O3" value="84.8" lower_limit="80.8" upper_limit="88.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5</title>
        <description>The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks &quot;How satisfied are you with the effect your treatment had on your facial lines?&quot; Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported.</description>
        <time_frame>Day 60</time_frame>
        <population>Intent-to-Treat: all randomized subjects with data reported at this time point</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
            <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA Dose B</title>
            <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
          <group group_id="O3">
            <title>OnabotulinumtoxinA Dose A</title>
            <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5</title>
          <description>The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks &quot;How satisfied are you with the effect your treatment had on your facial lines?&quot; Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported.</description>
          <population>Intent-to-Treat: all randomized subjects with data reported at this time point</population>
          <units>Percentage of Subjects</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="155"/>
                <count group_id="O2" value="317"/>
                <count group_id="O3" value="313"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" lower_limit="0.4" upper_limit="6.0"/>
                    <measurement group_id="O2" value="81.4" lower_limit="77.1" upper_limit="85.7"/>
                    <measurement group_id="O3" value="87.9" lower_limit="84.2" upper_limit="91.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points</title>
        <description>The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis.</description>
        <time_frame>Baseline, Day 30</time_frame>
        <population>Intent-to-Treat: all randomized subjects with baseline scores ≥ 20 on the Impact Domain of the FLSQ</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
            <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA Dose B</title>
            <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
          <group group_id="O3">
            <title>OnabotulinumtoxinA Dose A</title>
            <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points</title>
          <description>The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis.</description>
          <population>Intent-to-Treat: all randomized subjects with baseline scores ≥ 20 on the Impact Domain of the FLSQ</population>
          <units>Percentage of Subjects</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="152"/>
                <count group_id="O2" value="310"/>
                <count group_id="O3" value="301"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.7" lower_limit="13.4" upper_limit="26.1"/>
                    <measurement group_id="O2" value="61.0" lower_limit="55.5" upper_limit="66.4"/>
                    <measurement group_id="O3" value="76.1" lower_limit="71.3" upper_limit="80.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire©</title>
        <description>The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is &quot;I look older than my actual age because of my facial lines&quot; with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis.</description>
        <time_frame>Baseline, Day 30</time_frame>
        <population>Intent-to-Treat: all randomized subjects with baseline scores ≥ 3 on Item 4 of the FLO-11</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
            <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA Dose B</title>
            <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
          <group group_id="O3">
            <title>OnabotulinumtoxinA Dose A</title>
            <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire©</title>
          <description>The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is &quot;I look older than my actual age because of my facial lines&quot; with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis.</description>
          <population>Intent-to-Treat: all randomized subjects with baseline scores ≥ 3 on Item 4 of the FLO-11</population>
          <units>Percentage of Subjects</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="141"/>
                <count group_id="O2" value="285"/>
                <count group_id="O3" value="288"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.9" lower_limit="5.0" upper_limit="14.9"/>
                    <measurement group_id="O2" value="66.7" lower_limit="61.2" upper_limit="72.1"/>
                    <measurement group_id="O3" value="77.1" lower_limit="72.2" upper_limit="81.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Retreatment Eligibility</title>
        <description>Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis.</description>
        <time_frame>12 Months</time_frame>
        <population>Intent-to-Treat: all randomized subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
            <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
          </group>
          <group group_id="O2">
            <title>OnabotulinumtoxinA Dose B</title>
            <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
          <group group_id="O3">
            <title>OnabotulinumtoxinA Dose A</title>
            <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Retreatment Eligibility</title>
          <description>Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis.</description>
          <population>Intent-to-Treat: all randomized subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="143"/>
                <count group_id="O3" value="161"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.0" spread="NA">One incidence; therefore, SD not applicable</measurement>
                    <measurement group_id="O2" value="120.0" spread="46.4"/>
                    <measurement group_id="O3" value="126.0" spread="53.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A</title>
          <description>Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.</description>
        </group>
        <group group_id="E2">
          <title>OnabotulinumtoxinA Dose B</title>
          <description>OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
        </group>
        <group group_id="E3">
          <title>OnabotulinumtoxinA Dose A</title>
          <description>OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Meningitis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Fibula fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Ligament rupture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Lower limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Post procedural inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Tibia fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Intervertebral disc disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Large intestine benign neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Leiomyoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Lymphoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Malignant melanoma stage II</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of the tongue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neuritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Temporal lobe epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Abortion spontaneous</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="278"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="284"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Alcoholism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tonsillectomy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 19.0</default_vocab>
        <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="21" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="90" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="198" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="47" subjects_at_risk="746"/>
              </event>
              <event>
                <sub_title>Injection site haematoma</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="34" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="48" subjects_at_risk="746"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="156"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="318"/>
                <counts group_id="E3" subjects_affected="69" subjects_at_risk="746"/>
              </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>A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Tanya Brandstetter</name_or_title>
      <organization>Allergan, Inc</organization>
      <phone>714-246-2567</phone>
      <email>brandstetter_tanya@Allergan.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/NCT02261493
org study id: 191622-143
secondary id: 2014-001815-38
nct id: NCT02261493
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a safety and efficacy study of onabotulinumtoxinA in subjects with upper facial
      rhytides (forehead lines, glabellar lines, lateral canthal lines [crow's feet lines]).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation
time frame: Baseline, Day 30
description: The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported.
measure: Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation
time frame: Day 30
description: The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of "none" and "mild" are reported.
measure: Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest
time frame: Baseline, Day 30
description: The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported.
measure: Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5
time frame: Day 60
description: The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks "How satisfied are you with the effect your treatment had on your facial lines?" Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported.
measure: Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points
time frame: Baseline, Day 30
description: The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis.
measure: Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire©
time frame: Baseline, Day 30
description: The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is "I look older than my actual age because of my facial lines" with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis.
measure: Time to Retreatment Eligibility
time frame: 12 Months
description: Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis.
arm group label: OnabotulinumtoxinA Dose A
arm group type: Experimental
description: OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
arm group label: OnabotulinumtoxinA Dose B
arm group type: Experimental
description: OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
arm group label: Placebo followed by OnabotulinumtoxinA Dose A
arm group type: Placebo Comparator
description: Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.
intervention type: Biological
intervention name: OnabotulinumtoxinA
description: OnabotulinumtoxinA injected into the protocol-specified areas. Subjects will receive at least 1 and up to 3 treatments.
arm group label: OnabotulinumtoxinA Dose A
arm group label: OnabotulinumtoxinA Dose B
other name: BOTOX® Cosmetic
other name: botulinum toxin Type A
intervention type: Drug
intervention name: Normal Saline
description: Placebo (normal saline) injected into the protocol-specified areas on Day 1.
arm group label: Placebo followed by OnabotulinumtoxinA Dose A
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Allergan
facility: 
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country: Belgium
country: Germany
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Facies
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 