<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/NCT03282357</url>
  </required_header>
  <id_info>
    <org_study_id>M900311004</org_study_id>
    <nct_id>NCT03282357</nct_id>
  </id_info>
  <brief_title>Evaluation of the Effectiveness and Safety of Radiesse for the Correction of Nasolabial Folds in China</brief_title>
  <official_title>Evaluation of the Effectiveness and Safety of Radiesse for the Correction of Nasolabial Folds</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merz North America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merz North America, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this study are to evaluate the effectiveness and safety of Radiesse for the&#xD;
      correction of nasolabial folds (NLFs).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 27, 2017</start_date>
  <completion_date type="Actual">November 30, 2018</completion_date>
  <primary_completion_date type="Actual">July 17, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Split-face</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of NLFs With Treatment Success at Month 6</measure>
    <time_frame>Month 6</time_frame>
    <description>Treatment success was defined as a greater than or equal to (&gt;=) 1-point improvement from baseline, as assessed by a blinded evaluator wrinkle severity rating scale (WSRS) scale. WSRS is a 5 point scale with scores as Score 1: Absent; Score 2: Mild; Score 3: Moderate; Score 4: Severe; Score 5: Extreme.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of NLFs With an Improvement in the Blinded Evaluator's GAIS Score at Month 6</measure>
    <time_frame>Month 6</time_frame>
    <description>The blinded evaluator rated the current cosmetic result for each NLF according to the GAIS based on live assessments during the visit compared with photographs taken at baseline before administration of treatment on each NLF. An improvement on the GAIS was classified as &quot;improved&quot;, &quot;much improved&quot;, or &quot;very much improved. The GAIS is a 7-point scale, where: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), and -3 (very much worse).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">181</enrollment>
  <condition>Correction of the Moderate to Severe Nasolabial Folds</condition>
  <arm_group>
    <arm_group_label>Radiesse</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects are randomized as to which of the two nasolabial folds is treated with Radiesse.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Restylane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects are randomized as to which of the two nasolabial folds is treated with Restylane.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Radiesse injectable implant (dermal filler)</intervention_name>
    <description>Subdermal injection.</description>
    <arm_group_label>Radiesse</arm_group_label>
    <arm_group_label>Restylane</arm_group_label>
    <other_name>Calcium hydroxylapatite particles suspected in an aqueous based gel carrier.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Restylane injectable implant (dermal filler)</intervention_name>
    <description>Subdermal injection</description>
    <arm_group_label>Radiesse</arm_group_label>
    <arm_group_label>Restylane</arm_group_label>
    <other_name>Hyaluronic acid</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Is 22 - 65 years of age.&#xD;
&#xD;
          2. Has symmetrical NLFs of moderate or severe intensity (grade 3 or 4) on the WSRS as&#xD;
             determined by the independent blinded evaluator and confirmed by the treating&#xD;
             investigator at baseline.&#xD;
&#xD;
          3. Both folds must have the same NLF score at baseline. 4. Has signed an informed&#xD;
             consent.&#xD;
&#xD;
        5. Understands and accepts the obligation not to receive any other facial procedures below&#xD;
        the eyes during the study.&#xD;
&#xD;
        6. Understands and accepts the obligation to present for all scheduled follow-up visits and&#xD;
        is logistically able to meet all study requirements.&#xD;
&#xD;
        7. Subjects of childbearing potential must have a negative pregnancy test result and must&#xD;
        not be lactating at the Screening/Baseline Visit and be willing and able to use an&#xD;
        acceptable method of birth control (e.g. barrier methods used with a spermicidal agent,&#xD;
        hormonal methods, IUD, surgical sterilization, abstinence) during the study. Women will be&#xD;
        considered if one of the following conditions is documented on the medical history:&#xD;
&#xD;
          1. Postmenopausal with last menstrual bleeding at least 12 months prior to study; and&#xD;
&#xD;
          2. Without a uterus and/or both ovaries.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has received surgical permanent implants, grafting, or surgery below the eyes on the&#xD;
             face prior to injection or lower lid blepharoplasty within 6 months prior to&#xD;
             injection.&#xD;
&#xD;
          2. Has received within the specified (washout) period or plans to receive treatment&#xD;
             during the study conduct with a non-permanent facial filler in any facial area below&#xD;
             the eyes:&#xD;
&#xD;
               1. 12 months prior to study start - hyaluronic acid [HA] or collagen&#xD;
&#xD;
               2. 18 months prior to study start - calcium hydroxylapatite [CaHA]&#xD;
&#xD;
          3. Has received at any time or plans to receive during the study a permanent facial&#xD;
             filler (e.g. poly L-lactic acid [PLLA], polymethyl-methacrylate [PMMA], silicone)&#xD;
             below the eyes.&#xD;
&#xD;
          4. Has received within the past 6 months or plans to receive during the study facial&#xD;
             dermal resurfacing procedures (e.g. chemical peel, dermabrasion, ablative laser&#xD;
             resurfacing), non-invasive skin-tightening (e.g. Thermage), botulinum toxin&#xD;
             injections, mesotherapy, or fat injections below the eyes.&#xD;
&#xD;
          5. Has received in the past 2 weeks or plans to receive during the study any prescription&#xD;
             wrinkle therapies (e.g. RENOVAÒ), topical steroids, skin irritating topical&#xD;
             preparations, or pigmenting agents (self-tanning agents) for use on the face.&#xD;
&#xD;
          6. Has received in the past 2 months, or plans to receive immunosuppressive medications&#xD;
             or systemic steroids (intranasal/inhaled steroids acceptable) during the study.&#xD;
&#xD;
          7. Has an acute inflammatory process or infection, active herpes infection, or history of&#xD;
             chronic or recurrent infection or inflammation with the potential to interfere with&#xD;
             the study results or increase the risk of adverse events (AEs).&#xD;
&#xD;
          8. Has a known bleeding disorder or has received or is planning to receive&#xD;
             anti-coagulation, anti-platelet, or thrombolytic medications (e.g., warfarin),&#xD;
             anti-inflammatory drugs (oral/injectable corticosteroids or NSAIDs (e.g., aspirin,&#xD;
             ibuprofen), or other substances known to increase coagulation time (vitamins or herbal&#xD;
             supplements, e.g., Vitamin E, garlic, gingko), from 10 days before injection to 3 days&#xD;
             after injection.&#xD;
&#xD;
          9. Has a history of known liver or renal function disease/disorder or has clinically&#xD;
             significant laboratory values at baseline.&#xD;
&#xD;
         10. Has a known history of allergic/anaphylactic reactions, including hypersensitivity to&#xD;
             lidocaine or anesthetics of the amide type, or any of the device components.&#xD;
&#xD;
         11. Has a history of hyper- or hypo-pigmentation in the NLFs, keloid formation, or&#xD;
             hypertrophic scarring.&#xD;
&#xD;
         12. Has recently lost or has the intention to lose a significant amount of weight ≥ 2 Body&#xD;
             Mass Index (BMI) units during the course of the study.&#xD;
&#xD;
         13. Has any other medical condition with the potential to interfere with the study's&#xD;
             conduct or assessments, or increase the risk of AEs.&#xD;
&#xD;
         14. Has participated in a study in the last 30 days or is enrolled or plans to enroll in&#xD;
             any other interfering investigational study during participation in the study.&#xD;
&#xD;
         15. Is an employee or direct relative of an employee of the investigational department in&#xD;
             site or the sponsor.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Merz Medical Expert</last_name>
    <role>Study Director</role>
    <affiliation>Merz North America, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking University First Hospital, Merz Investigational Site #0860003</name>
      <address>
        <city>Beijing</city>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Medical University, Nanfang Hospital, Merz Investigational Site #0860006</name>
      <address>
        <city>Guangzhou</city>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhejiang Provincial People's Hospital, Merz Investigational Site #0860005</name>
      <address>
        <city>Hangzhou</city>
        <zip>310014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xiangya Hospital Central South University, Department of Aesthetic Plastic Surgery, Merz Investigational Site #'0860007</name>
      <address>
        <city>Hunan</city>
        <zip>410008</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <results_first_submitted>November 23, 2020</results_first_submitted>
  <results_first_submitted_qc>February 19, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 23, 2021</results_first_posted>
  <last_update_submitted>February 19, 2021</last_update_submitted>
  <last_update_submitted_qc>February 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyaluronic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03282357/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 17, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03282357/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 4 investigative sites in China.</recruitment_details>
      <pre_assignment_details>A total of 195 participants were screened, out of which 181 were randomized. Of these, 176 participants were treated and 164 participants completed the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Radiesse and Restylane</title>
          <description>Participants received split-face nasolabial fold (NLF) treatment with study product Radiesse, subdermal injection, in one of the two NLFs and control product Restylane, subdermal injection, in the contralateral NLF on Day 1. Participants received an optional touch-up injection in one or both the NLFs at Month 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="181"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Evaluation Set</title>
              <participants_list>
                <participants group_id="P1" count="176"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="164"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety evaluation set (SES) was defined as all participants who received an investigational product.</population>
      <group_list>
        <group group_id="B1">
          <title>Radiesse and Restylane</title>
          <description>Participants received split-face NLF treatment with study product Radiesse, subdermal injection, in one of the two NLFs and control product Restylane, subdermal injection, in the contralateral NLF on Day 1. Participants received an optional touch-up injection in one or both the NLFs at Month 1.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="176"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.6" spread="9.43"/>
                  </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="170"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ethnicity</title>
              <category_list>
                <category>
                  <title>Han Chinese</title>
                  <measurement_list>
                    <measurement group_id="B1" value="173"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race (Asian)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fitzpatrick skin type</title>
          <description>Skin type I = white; very fair, red or blonde hair blue eyes; freckles; always burns, never tans, skin type II = white, fair, red or blond hair; blue, hazel or green eyes; usually burns, tans with difficulty, skin type III = cream white; fair with any eye or hair color (common); sometimes mild burn, gradually tans, skin type IV = brown; typical Mediterranean Caucasian skin; rarely burns, tans with ease, skin type V = dark brown; mid-eastern skin types; very rarely burns, tans easily, and skin type VI = black; never burns, tans very easily.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Type I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="147"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type IV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type V</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type VI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeter (cm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="159.9" spread="5.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilogram (Kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.15" spread="8.434"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kilogram per square meter (kg/m^2)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21.87" spread="2.817"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of NLFs With Treatment Success at Month 6</title>
        <description>Treatment success was defined as a greater than or equal to (&gt;=) 1-point improvement from baseline, as assessed by a blinded evaluator wrinkle severity rating scale (WSRS) scale. WSRS is a 5 point scale with scores as Score 1: Absent; Score 2: Mild; Score 3: Moderate; Score 4: Severe; Score 5: Extreme.</description>
        <time_frame>Month 6</time_frame>
        <population>The per protocol set (PPS) was the subset of the full analysis set (FAS) without any major protocol deviations. The FAS was all participants randomized who received an investigational product with at least one post-baseline effectiveness assessment (WSRS, blind evaluator's Global Aesthetic Improvement Scale [GAIS] or participant's GAIS assessment).</population>
        <group_list>
          <group group_id="O1">
            <title>Radiesse</title>
            <description>All participants received NLF treatment with study product Radiesse, subdermal injection, in one of the two NLFs on Day 1. Participants received an optional touch-up injection in the same NLF at Month 1.</description>
          </group>
          <group group_id="O2">
            <title>Restylane</title>
            <description>All participants received NLF treatment with control product Restylane, subdermal injection, in the contralateral NLF on Day 1. Participants received an optional touch-up injection in the same NLFs at Month 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of NLFs With Treatment Success at Month 6</title>
          <description>Treatment success was defined as a greater than or equal to (&gt;=) 1-point improvement from baseline, as assessed by a blinded evaluator wrinkle severity rating scale (WSRS) scale. WSRS is a 5 point scale with scores as Score 1: Absent; Score 2: Mild; Score 3: Moderate; Score 4: Severe; Score 5: Extreme.</description>
          <population>The per protocol set (PPS) was the subset of the full analysis set (FAS) without any major protocol deviations. The FAS was all participants randomized who received an investigational product with at least one post-baseline effectiveness assessment (WSRS, blind evaluator's Global Aesthetic Improvement Scale [GAIS] or participant's GAIS assessment).</population>
          <units>Percentage of successfully treated NFLs</units>
          <param>Number</param>
          <units_analyzed>Nasolabial fold (NLF)</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="171"/>
                <count group_id="O2" value="171"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Nasolabial fold (NLF)</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="171"/>
                <count group_id="O2" value="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.0"/>
                    <measurement group_id="O2" value="72.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority margin, delta = 10 percent (%). The two-sided 95% confidence interval (CI) for the differences between percentages was constructed using the Newcombe's recommended method.</non_inferiority_desc>
            <param_type>Difference in Percentage</param_type>
            <param_value>-6.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-13.1</ci_lower_limit>
            <ci_upper_limit>-0.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of NLFs With an Improvement in the Blinded Evaluator's GAIS Score at Month 6</title>
        <description>The blinded evaluator rated the current cosmetic result for each NLF according to the GAIS based on live assessments during the visit compared with photographs taken at baseline before administration of treatment on each NLF. An improvement on the GAIS was classified as &quot;improved&quot;, &quot;much improved&quot;, or &quot;very much improved. The GAIS is a 7-point scale, where: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), and -3 (very much worse).</description>
        <time_frame>Month 6</time_frame>
        <population>The PPS was defined as the subset of the FAS without any major protocol deviations. The FAS was defined as all participants randomized and who received an investigational product with at least one post-baseline effectiveness assessment (that is WSRS, blind evaluator's GAIS or participant's GAIS assessment).</population>
        <group_list>
          <group group_id="O1">
            <title>Radiesse</title>
            <description>All participants received NLF treatment with study product Radiesse, subdermal injection, in one of the two NLFs on Day 1. Participants received an optional touch-up injection in the same NLF at Month 1.</description>
          </group>
          <group group_id="O2">
            <title>Restylane</title>
            <description>All participants received NLF treatment with control product Restylane, subdermal injection, in the contralateral NLF on Day 1. Participants received an optional touch-up injection in the same NLFs at Month 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of NLFs With an Improvement in the Blinded Evaluator's GAIS Score at Month 6</title>
          <description>The blinded evaluator rated the current cosmetic result for each NLF according to the GAIS based on live assessments during the visit compared with photographs taken at baseline before administration of treatment on each NLF. An improvement on the GAIS was classified as &quot;improved&quot;, &quot;much improved&quot;, or &quot;very much improved. The GAIS is a 7-point scale, where: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), and -3 (very much worse).</description>
          <population>The PPS was defined as the subset of the FAS without any major protocol deviations. The FAS was defined as all participants randomized and who received an investigational product with at least one post-baseline effectiveness assessment (that is WSRS, blind evaluator's GAIS or participant's GAIS assessment).</population>
          <units>Percentage of NLFs</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="171"/>
                <count group_id="O2" value="171"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.4"/>
                    <measurement group_id="O2" value="83.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority margin, delta = 15%. The two-sided 95% CI for the differences between percentages was constructed using the Newcombe's recommended method.</non_inferiority_desc>
            <param_type>Difference in Percentage</param_type>
            <param_value>-4.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.8</ci_lower_limit>
            <ci_upper_limit>-0.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Month 12</time_frame>
      <desc>The investigator asked the participant for adverse events (AEs) systematically at each visit. The SES was used for AE assessment. The SES was defined as all participants who received an investigational product.&#xD;
As all participants received Radiesse in either of the two nasolabial folds and Restylane in the respective other, adverse events are reported in a combined group.</desc>
      <group_list>
        <group group_id="E1">
          <title>Radiesse and Restylane</title>
          <description>Participants received split-face NLF treatment with study product Radiesse, subdermal injection, in one of the two NLFs and control product Restylane, subdermal injection, in the contralateral NLF on Day 1. Participants received an optional touch-up injection in one or both the NLFs at Month 1.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="176"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="176"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="176"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="176"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="176"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical dysplasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="176"/>
              </event>
              <event>
                <sub_title>Endometrial thickening</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="176"/>
              </event>
              <event>
                <sub_title>Uterine haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="176"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="56" subjects_at_risk="176"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site nodule</sub_title>
                <description>8 (4.5%) participants experienced this event at the Radiesse injection site, 9 (5.1%) at the Restylane injection site.</description>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="176"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="176"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="176"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="176"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperlipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="176"/>
              </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>Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the investigator will consider these doubts in the publication as long as the scientific neutrality is not affected.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Public Disclosure Manager</name_or_title>
      <organization>Merz Pharmaceuticals GmbH.</organization>
      <phone>+49 69 1503 1</phone>
      <email>clinicaltrials@merz.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/NCT03282357
org study id: M900311004
nct id: NCT03282357
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
The objectives of this study are to evaluate the effectiveness and safety of Radiesse for the
      correction of nasolabial folds (NLFs).
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: Split-face
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Percentage of NLFs With Treatment Success at Month 6
time frame: Month 6
description: Treatment success was defined as a greater than or equal to (>=) 1-point improvement from baseline, as assessed by a blinded evaluator wrinkle severity rating scale (WSRS) scale. WSRS is a 5 point scale with scores as Score 1: Absent; Score 2: Mild; Score 3: Moderate; Score 4: Severe; Score 5: Extreme.
measure: Percentage of NLFs With an Improvement in the Blinded Evaluator's GAIS Score at Month 6
time frame: Month 6
description: The blinded evaluator rated the current cosmetic result for each NLF according to the GAIS based on live assessments during the visit compared with photographs taken at baseline before administration of treatment on each NLF. An improvement on the GAIS was classified as "improved", "much improved", or "very much improved. The GAIS is a 7-point scale, where: +3 (very much improved), +2 (much improved), +1 (improved), 0 (no change), -1 (worse), -2 (much worse), and -3 (very much worse).
arm group label: Radiesse
arm group type: Experimental
description: Subjects are randomized as to which of the two nasolabial folds is treated with Radiesse.
arm group label: Restylane
arm group type: Active Comparator
description: Subjects are randomized as to which of the two nasolabial folds is treated with Restylane.
intervention type: Device
intervention name: Radiesse injectable implant (dermal filler)
description: Subdermal injection.
arm group label: Radiesse
arm group label: Restylane
other name: Calcium hydroxylapatite particles suspected in an aqueous based gel carrier.
intervention type: Device
intervention name: Restylane injectable implant (dermal filler)
description: Subdermal injection
arm group label: Radiesse
arm group label: Restylane
other name: Hyaluronic acid
criteria: 
gender: All
minimum age: 22 Years
maximum age: 65 Years
healthy volunteers: No
last name: Merz Medical Expert
role: Study Director
affiliation: Merz North America, Inc.
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Hyaluronic Acid
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 