<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/NCT03273543</url>
  </required_header>
  <id_info>
    <org_study_id>REST-DEF-2017</org_study_id>
    <nct_id>NCT03273543</nct_id>
  </id_info>
  <brief_title>Perioral Rejuvenation and Upper Lip Enhancement</brief_title>
  <official_title>Premaxillary Injection for Perioral Rejuvenation and Upper Lip Enhancement</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>DeNova Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>DeNova Research</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine if subjects who receive premaxillary injection demonstrate an increase in nasal&#xD;
      tip projection and an associated increase in upper lip projection, and vermillion height.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 20, 2017</start_date>
  <completion_date type="Actual">July 3, 2018</completion_date>
  <primary_completion_date type="Actual">July 3, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Nasal Tip Projection</measure>
    <time_frame>Baseline and 2 months</time_frame>
    <description>Baseline nasal projection measurements will be documented according to Goode's ratio.&#xD;
The Goode ratio was used as a measurement of tip projection and is defined as the ratio of the nasal height in relation to the nasal length. For each subject's right lateral view photograph, the nasal height was measured as the length of a line drawn from the alar-facial groove to the tip-defining point, and the nasal length was measured as the length of the line drawn from the nasion to the tip-defining point. The nasal height value was then divided by the nasal length value to determine the Goode ratio for a given photograph.&#xD;
The ratio of the line from the alar crease to the nasal tip to the nasion to the nasal tip should be . 55. If it is more than that the nose is overprojected, if it is under that ratio the nose is underprojected.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Upper Lip Projection</measure>
    <time_frame>Baseline and 2 months</time_frame>
    <description>baseline upper lip position will recorded by measuring the Z-angle, which is the intersection of the Frankfort horizontal line and the profile line as described by Merrifield. From the straight portrait image, the ratio of the upper lip vermillion height to the lower lip vermillion height will be documented.&#xD;
Upper lip projection was assessed via measurement of the Z angle. On each subject's right lateral view photograph, a profile line was drawn tangential to the pogonion of the chin and to the most anterior point of the upper lip. A second line was drawn along the Frankfort horizontal plane. The resulting angle at which these two lines intersected corresponded to the Z angle. A decrease in the Z angle to a more acute value on post-treatment photographs would correspond to an increase in upper lip projection.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Perioral Rejuvenation</condition>
  <condition>Upper Lip Projection</condition>
  <arm_group>
    <arm_group_label>Nasal Tip Projection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Upper Lip Position</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Restylane® Defyne</intervention_name>
    <description>hyaluronic acid filler injection</description>
    <arm_group_label>Nasal Tip Projection</arm_group_label>
    <arm_group_label>Upper Lip Position</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Subjects Age 21 to 70. 2. Subjects who demonstrate signs of perioral aging or poor&#xD;
             upper lip projection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Subjects who plan to undergo peri oral neurotoxin treatments or ablative skin&#xD;
             treatments, or have had either of these treatments in the previous 6 months, other&#xD;
             injectable filler treatments during the course of the study.&#xD;
&#xD;
             2. Subjects who are pregnant or nursing. 3. Subjects with a known allergy or&#xD;
             sensitivity to any component of the study ingredients.&#xD;
&#xD;
             4. Any history of rhinoplasty or nasal filler injections. 5. Recent history of upper&#xD;
             lip augmentation (surgical and non-surgical) within the last 12 months.&#xD;
&#xD;
             6. Any history of lip lift or other surgical procedures involving the upper lip.&#xD;
&#xD;
             7. Any history of chin augmentation (surgical and non-surgical). 8. Any history of&#xD;
             orthognathic surgery. 9. Any history of bleeding disorders (iatrogenic or otherwise).&#xD;
             10. Current history of chronic drug or alcohol abuse. 11. Concurrent therapy that, in&#xD;
             the investigator's opinion, would interfere with the evaluation of the safety or&#xD;
             efficacy of the study product (i.e. immunosuppressive therapy).&#xD;
&#xD;
             12. Subjects who, in the Investigator's opinion, have a history of poor cooperation,&#xD;
             non¬compliance with medical treatment or unreliability.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven H Dayan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>DeNova Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>DeNova Research</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <results_first_submitted>August 11, 2020</results_first_submitted>
  <results_first_submitted_qc>September 15, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 8, 2020</results_first_posted>
  <last_update_submitted>September 15, 2020</last_update_submitted>
  <last_update_submitted_qc>September 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>DeNova Research</investigator_affiliation>
    <investigator_full_name>Steven H. Dayan</investigator_full_name>
    <investigator_title>MD, FACS</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 12, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT03273543/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Nasal Tip Projection</title>
          <description>Restylane® Defyne: hyaluronic acid filler injection</description>
        </group>
        <group group_id="P2">
          <title>Upper Lip Position</title>
          <description>Restylane® Defyne: hyaluronic acid filler injection</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Nasal Tip Projection</title>
          <description>Restylane® Defyne: hyaluronic acid filler injection</description>
        </group>
        <group group_id="B2">
          <title>Upper Lip Position</title>
          <description>Restylane® Defyne: hyaluronic acid filler injection</description>
        </group>
        <group group_id="B3">
          <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="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.8" spread="0"/>
                    <measurement group_id="B2" value="41.2" spread="0"/>
                    <measurement group_id="B3" value="39" spread="0"/>
                  </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="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Nasal Tip Projection</title>
        <description>Baseline nasal projection measurements will be documented according to Goode's ratio.&#xD;
The Goode ratio was used as a measurement of tip projection and is defined as the ratio of the nasal height in relation to the nasal length. For each subject's right lateral view photograph, the nasal height was measured as the length of a line drawn from the alar-facial groove to the tip-defining point, and the nasal length was measured as the length of the line drawn from the nasion to the tip-defining point. The nasal height value was then divided by the nasal length value to determine the Goode ratio for a given photograph.&#xD;
The ratio of the line from the alar crease to the nasal tip to the nasion to the nasal tip should be . 55. If it is more than that the nose is overprojected, if it is under that ratio the nose is underprojected.</description>
        <time_frame>Baseline and 2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nasal Tip Projection</title>
            <description>Restylane® Defyne: hyaluronic acid filler injection&#xD;
Mean nasal tip projection measured by comparing baseline vs post-tx Goode's Ratio</description>
          </group>
        </group_list>
        <measure>
          <title>Nasal Tip Projection</title>
          <description>Baseline nasal projection measurements will be documented according to Goode's ratio.&#xD;
The Goode ratio was used as a measurement of tip projection and is defined as the ratio of the nasal height in relation to the nasal length. For each subject's right lateral view photograph, the nasal height was measured as the length of a line drawn from the alar-facial groove to the tip-defining point, and the nasal length was measured as the length of the line drawn from the nasion to the tip-defining point. The nasal height value was then divided by the nasal length value to determine the Goode ratio for a given photograph.&#xD;
The ratio of the line from the alar crease to the nasal tip to the nasion to the nasal tip should be . 55. If it is more than that the nose is overprojected, if it is under that ratio the nose is underprojected.</description>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.601" spread="0.052"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Upper Lip Projection</title>
        <description>baseline upper lip position will recorded by measuring the Z-angle, which is the intersection of the Frankfort horizontal line and the profile line as described by Merrifield. From the straight portrait image, the ratio of the upper lip vermillion height to the lower lip vermillion height will be documented.&#xD;
Upper lip projection was assessed via measurement of the Z angle. On each subject's right lateral view photograph, a profile line was drawn tangential to the pogonion of the chin and to the most anterior point of the upper lip. A second line was drawn along the Frankfort horizontal plane. The resulting angle at which these two lines intersected corresponded to the Z angle. A decrease in the Z angle to a more acute value on post-treatment photographs would correspond to an increase in upper lip projection.</description>
        <time_frame>Baseline and 2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Upper Lip Position</title>
            <description>Restylane® Defyne: hyaluronic acid filler injection</description>
          </group>
        </group_list>
        <measure>
          <title>Upper Lip Projection</title>
          <description>baseline upper lip position will recorded by measuring the Z-angle, which is the intersection of the Frankfort horizontal line and the profile line as described by Merrifield. From the straight portrait image, the ratio of the upper lip vermillion height to the lower lip vermillion height will be documented.&#xD;
Upper lip projection was assessed via measurement of the Z angle. On each subject's right lateral view photograph, a profile line was drawn tangential to the pogonion of the chin and to the most anterior point of the upper lip. A second line was drawn along the Frankfort horizontal plane. The resulting angle at which these two lines intersected corresponded to the Z angle. A decrease in the Z angle to a more acute value on post-treatment photographs would correspond to an increase in upper lip projection.</description>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.245" spread="10.859"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Nasal Tip Projection</title>
          <description>Restylane® Defyne: hyaluronic acid filler injection</description>
        </group>
        <group group_id="E2">
          <title>Upper Lip Position</title>
          <description>Restylane® Defyne: hyaluronic acid filler injection</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Steven Dayan, MD</name_or_title>
      <organization>DeNova Research</organization>
      <phone>3123352070</phone>
      <email>sdayan@drdayan.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/NCT03273543
org study id: REST-DEF-2017
nct id: NCT03273543
lead sponsor: 
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: Yes
To determine if subjects who receive premaxillary injection demonstrate an increase in nasal
      tip projection and an associated increase in upper lip projection, and vermillion height.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Nasal Tip Projection
time frame: Baseline and 2 months
description: Baseline nasal projection measurements will be documented according to Goode's ratio.
The Goode ratio was used as a measurement of tip projection and is defined as the ratio of the nasal height in relation to the nasal length. For each subject's right lateral view photograph, the nasal height was measured as the length of a line drawn from the alar-facial groove to the tip-defining point, and the nasal length was measured as the length of the line drawn from the nasion to the tip-defining point. The nasal height value was then divided by the nasal length value to determine the Goode ratio for a given photograph.
The ratio of the line from the alar crease to the nasal tip to the nasion to the nasal tip should be . 55. If it is more than that the nose is overprojected, if it is under that ratio the nose is underprojected.
measure: Upper Lip Projection
time frame: Baseline and 2 months
description: baseline upper lip position will recorded by measuring the Z-angle, which is the intersection of the Frankfort horizontal line and the profile line as described by Merrifield. From the straight portrait image, the ratio of the upper lip vermillion height to the lower lip vermillion height will be documented.
Upper lip projection was assessed via measurement of the Z angle. On each subject's right lateral view photograph, a profile line was drawn tangential to the pogonion of the chin and to the most anterior point of the upper lip. A second line was drawn along the Frankfort horizontal plane. The resulting angle at which these two lines intersected corresponded to the Z angle. A decrease in the Z angle to a more acute value on post-treatment photographs would correspond to an increase in upper lip projection.
arm group label: Nasal Tip Projection
arm group type: Experimental
arm group label: Upper Lip Position
arm group type: Experimental
intervention type: Device
intervention name: Restylane® Defyne
description: hyaluronic acid filler injection
arm group label: Nasal Tip Projection
arm group label: Upper Lip Position
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Steven H Dayan, MD
role: Principal Investigator
affiliation: DeNova Research
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: DeNova Research
investigator full name: Steven H. Dayan
investigator title: MD, FACS
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 