<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/NCT02193828</url>
  </required_header>
  <id_info>
    <org_study_id>AUX-CC-750</org_study_id>
    <nct_id>NCT02193828</nct_id>
  </id_info>
  <brief_title>Phase 2a Dose-Ranging Study to Evaluate Safety and Effectiveness of AA4500 in Treatment of Dupuytren's Disease Nodules</brief_title>
  <official_title>A Phase 2a, Double-blind, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Effectiveness of AA4500 in the Treatment of Dupuytren's Disease Nodules</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Endo Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Endo Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of this study are to assess the safety and effectiveness of AA4500 in treating&#xD;
      palmar Dupuytren's disease nodules.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximately 13 sites in the United States and Australia, approximately 90 study subjects.&#xD;
&#xD;
      After all pre-injection procedures are completed on day 1, eligible men and women will be&#xD;
      randomized in a 1:1:1 ratio to dose group and then in a 4:1 ratio to treatment group. Study&#xD;
      drug will be administered into a palmar nodule located on the selected hand.&#xD;
&#xD;
      AA4500 (collagenase clostridium histolyticum) 3 doses (low, medium, and high) after&#xD;
      reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium&#xD;
      chloride). Each dose of study drug will be injected into the nodule. The injection will be&#xD;
      administered in 3 different volumes according to randomization.&#xD;
&#xD;
      Placebo after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in&#xD;
      0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The&#xD;
      injection will be administered in 3 different volumes according to randomization.&#xD;
&#xD;
      Follow up visits for the evaluation of safety and efficacy will be required for all subjects&#xD;
      on days 8, 29, and 57.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements</measure>
    <time_frame>Baseline, Day 57</time_frame>
    <description>Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound</measure>
    <time_frame>Baseline, Day 57</time_frame>
    <description>Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Consistency of the Treated Nodules at Day 57</measure>
    <time_frame>Baseline, Day 57</time_frame>
    <description>Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Hardness of the Treated Nodule at Day 57</measure>
    <time_frame>Baseline, Day 57</time_frame>
    <description>A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Nodular Pain of the Treated Nodule at Day 57</measure>
    <time_frame>Baseline, Day 57</time_frame>
    <description>After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator Global Assessment of Improvement With Treatment</measure>
    <time_frame>Day 57</time_frame>
    <description>Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject Satisfaction With Treatment</measure>
    <time_frame>Day 57</time_frame>
    <description>Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Responder Analysis</measure>
    <time_frame>Day 57</time_frame>
    <description>A composite responder is a subject who had an improved assessment [values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)] on the investigator global assessment and had a satisfied assessment [values of 1 (very satisfied) or 2 (quite satisfied)] on the subject assessment.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">76</enrollment>
  <condition>Dupuytren's Disease</condition>
  <arm_group>
    <arm_group_label>AA4500 0.25 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Collagenase clostridium histolyticum, single 0.25 mg injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AA4500 0.40 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Collagenase clostridium histolyticum, single 0.40 mg injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AA4500 0.60 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Collagenase clostridium histolyticum, single 0.60 mg injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Collagenase clostridium histolyticum</intervention_name>
    <description>Single injection into nodule</description>
    <arm_group_label>AA4500 0.25 mg</arm_group_label>
    <arm_group_label>AA4500 0.40 mg</arm_group_label>
    <arm_group_label>AA4500 0.60 mg</arm_group_label>
    <other_name>AA4500</other_name>
    <other_name>XIAFLEX</other_name>
    <other_name>XIAPEX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single injection into nodule</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provide a signed and dated informed consent&#xD;
&#xD;
          2. Be a man or woman ≥ 18 years of age&#xD;
&#xD;
          3. Have a diagnosis of Dupuytren's disease AND have at least one palmar nodule on the&#xD;
             selected hand that is:&#xD;
&#xD;
               1. Palpable&#xD;
&#xD;
               2. Measures between 0.5 cm and 2.0 cm in length and between 0.5 cm and 2.0 cm in&#xD;
                  width using hand-held calipers n&#xD;
&#xD;
               3. Not directly associated with a Dupuytren's cord&#xD;
&#xD;
          4. Have a negative urine pregnancy test at screening and before injection of study drug&#xD;
             and be using a highly effective (ie, &lt; 1% failure rate) contraception method as judged&#xD;
             by the investigator (eg, abstinence, intrauterine device [IUD], hormonal&#xD;
             [estrogen/progestin] contraceptives, or barrier control) for at least one menstrual&#xD;
             cycle prior to study enrollment and for the duration of the study or be surgically&#xD;
             sterile (if female of childbearing potential); or be a postmenopausal female (no&#xD;
             menses for at least 1 year or hysterectomy)&#xD;
&#xD;
          5. Be able to comply with the study visit schedule as specified in the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received steroid injections (eg, tri-amcinolone acetonide) on the selected nodule&#xD;
             within 3 months before administration of study drug&#xD;
&#xD;
          2. Has a chronic muscular, neurological, or neuromuscular disorder that affects the hands&#xD;
&#xD;
          3. Has a known systemic allergy to collagenase or any other excipient of AA4500&#xD;
&#xD;
          4. Has received any collagenase treatments (eg, Santyl® ointment and/or XIAFLEX®/XIAPEX®)&#xD;
             within 30 days before injection of study drug in the hand selected for treatment&#xD;
&#xD;
          5. Is currently receiving or plans to receive anticoagulant medication or has received&#xD;
             anticoagulant medication (except for ≤ 150 mg aspirin daily) within 7 days before&#xD;
             injection of study drug&#xD;
&#xD;
          6. Has a known recent history of stroke, bleeding, or other medical condition, which in&#xD;
             the investigator's opinion would make the subject unsuitable for enrollment in the&#xD;
             study&#xD;
&#xD;
          7. Received an investigational drug within 30 days before injection of study drug&#xD;
&#xD;
          8. Is pregnant or intends on becoming pregnant during the study or is breastfeeding a&#xD;
             child&#xD;
&#xD;
          9. Has any clinically significant medical history or condition(s), including conditions&#xD;
             that affect the hands, that would, in the opinion of the investigator, substantially&#xD;
             increase the risk associated with the subject's participation in the protocol or&#xD;
             compromise the scientific objectives of the study&#xD;
&#xD;
         10. Had surgery on the selected hand within 3 months before the screening visit&#xD;
&#xD;
         11. Has jewelry on the hand to be treated that cannot be removed&#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>Veronica Urdaneta, MD MPH</last_name>
    <role>Study Director</role>
    <affiliation>Endo Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tucson Orthopaedic Institute</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CORE Orthopaedic Medical Center</name>
      <address>
        <city>Encinitas</city>
        <state>California</state>
        <zip>92024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marin Endocrine Care &amp; Research, Inc.</name>
      <address>
        <city>Greenbrae</city>
        <state>California</state>
        <zip>94904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigid Freyne, MD, Inc.</name>
      <address>
        <city>Murrieta</city>
        <state>California</state>
        <zip>92563</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana Hand to Shoulder Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State University of New York</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OrthoCarolina Research Institute, Inc.</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orthopedic and Reconstructive Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blair Orthopedic Associates, Inc.</name>
      <address>
        <city>Altoona</city>
        <state>Pennsylvania</state>
        <zip>16602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brisbane Hand &amp; Upper Limb Clinic</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Medical</name>
      <address>
        <city>Kippa Ring</city>
        <state>Queensland</state>
        <zip>4021</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>June 19, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <results_first_submitted>June 12, 2015</results_first_submitted>
  <results_first_submitted_qc>June 12, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">July 7, 2015</results_first_posted>
  <last_update_submitted>September 7, 2017</last_update_submitted>
  <last_update_submitted_qc>September 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dupuytren's nodules</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dupuytren Contracture</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>AA4500 0.60 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
        </group>
        <group group_id="P2">
          <title>AA4500 0.40 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
        </group>
        <group group_id="P3">
          <title>AA4500 0.25 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
                <participants group_id="P3" count="23"/>
                <participants group_id="P4" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
                <participants group_id="P3" count="22"/>
                <participants group_id="P4" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysis based on Safety population; all randomized subjects who received an injection of study medication. One subject did not receive study medication.</population>
      <group_list>
        <group group_id="B1">
          <title>AA4500 0.60 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
        </group>
        <group group_id="B2">
          <title>AA4500 0.40 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
        </group>
        <group group_id="B3">
          <title>AA4500 0.25 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
        </group>
        <group group_id="B5">
          <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="18"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="22"/>
            <count group_id="B4" value="17"/>
            <count group_id="B5" value="75"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.0" lower_limit="41" upper_limit="84"/>
                    <measurement group_id="B2" value="60.0" lower_limit="37" upper_limit="75"/>
                    <measurement group_id="B3" value="57.0" lower_limit="32" upper_limit="73"/>
                    <measurement group_id="B4" value="58.0" lower_limit="45" upper_limit="73"/>
                    <measurement group_id="B5" value="58.0" lower_limit="32" upper_limit="84"/>
                  </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="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="16"/>
                    <measurement group_id="B5" value="71"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="22"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="74"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements</title>
        <description>Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.</description>
        <time_frame>Baseline, Day 57</time_frame>
        <population>Analysis based on Modified Intent-to-Treat (mITT) population; all randomized subjects who received study medication and had pre- and post-baseline nodule measurements for ultrasound and calipers. Analytical outliers (subjects whose percent change in ultrasound volume was greater than the 75th percentile + 3× the interquartile range) were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500 0.60 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
          </group>
          <group group_id="O2">
            <title>AA4500 0.40 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
          </group>
          <group group_id="O3">
            <title>AA4500 0.25 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements</title>
          <description>Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.</description>
          <population>Analysis based on Modified Intent-to-Treat (mITT) population; all randomized subjects who received study medication and had pre- and post-baseline nodule measurements for ultrasound and calipers. Analytical outliers (subjects whose percent change in ultrasound volume was greater than the 75th percentile + 3× the interquartile range) were excluded.</population>
          <units>percentage of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="20"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Surface Area</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-81.61" spread="20.251"/>
                    <measurement group_id="O2" value="-80.11" spread="21.459"/>
                    <measurement group_id="O3" value="-58.30" spread="29.849"/>
                    <measurement group_id="O4" value="-41.76" spread="32.445"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Volume</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-89.03" spread="15.016"/>
                    <measurement group_id="O2" value="-87.58" spread="16.372"/>
                    <measurement group_id="O3" value="-68.15" spread="33.859"/>
                    <measurement group_id="O4" value="-49.13" spread="36.736"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For surface area</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For surface area</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For surface area</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For surface area</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0713</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For volume</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0002</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For volume</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0001</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For volume</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0001</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For volume</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0446</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound</title>
        <description>Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.</description>
        <time_frame>Baseline, Day 57</time_frame>
        <population>Analysis based on mITT population; all randomized subjects who received study medication and had pre- and post-baseline nodule measurements for ultrasound and calipers. Analytical outliers (subjects whose percent change in ultrasound volume was greater than the 75th percentile + 3× the interquartile range) were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500 0.60 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
          </group>
          <group group_id="O2">
            <title>AA4500 0.40 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
          </group>
          <group group_id="O3">
            <title>AA4500 0.25 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound</title>
          <description>Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.</description>
          <population>Analysis based on mITT population; all randomized subjects who received study medication and had pre- and post-baseline nodule measurements for ultrasound and calipers. Analytical outliers (subjects whose percent change in ultrasound volume was greater than the 75th percentile + 3× the interquartile range) were excluded.</population>
          <units>percentage of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="20"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Surface Area</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-34.23" spread="41.353"/>
                    <measurement group_id="O2" value="-19.37" spread="39.658"/>
                    <measurement group_id="O3" value="-10.30" spread="41.696"/>
                    <measurement group_id="O4" value="-4.54" spread="54.784"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Volume</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-40.99" spread="46.612"/>
                    <measurement group_id="O2" value="-13.01" spread="68.804"/>
                    <measurement group_id="O3" value="-9.52" spread="60.156"/>
                    <measurement group_id="O4" value="-7.19" spread="69.877"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For surface area</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.2431</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For surface area</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0625</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For surface area</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.3409</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For surface area</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.7040</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For volume</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.3556</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For volume</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.1275</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For volume</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.7883</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For volume</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.9123</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Consistency of the Treated Nodules at Day 57</title>
        <description>Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening.</description>
        <time_frame>Baseline, Day 57</time_frame>
        <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500 0.60 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
          </group>
          <group group_id="O2">
            <title>AA4500 0.40 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
          </group>
          <group group_id="O3">
            <title>AA4500 0.25 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Consistency of the Treated Nodules at Day 57</title>
          <description>Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening.</description>
          <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="22"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="0.93"/>
                    <measurement group_id="O2" value="-1.9" spread="1.05"/>
                    <measurement group_id="O3" value="-1.2" spread="1.10"/>
                    <measurement group_id="O4" value="-0.3" spread="0.96"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0002</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0002</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0139</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Hardness of the Treated Nodule at Day 57</title>
        <description>A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening.</description>
        <time_frame>Baseline, Day 57</time_frame>
        <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500 0.60 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
          </group>
          <group group_id="O2">
            <title>AA4500 0.40 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
          </group>
          <group group_id="O3">
            <title>AA4500 0.25 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Hardness of the Treated Nodule at Day 57</title>
          <description>A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening.</description>
          <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.</population>
          <units>percentage of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="22"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.05" spread="15.584"/>
                    <measurement group_id="O2" value="-30.40" spread="24.930"/>
                    <measurement group_id="O3" value="-17.87" spread="22.265"/>
                    <measurement group_id="O4" value="4.80" spread="23.959"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0004</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0075</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0031</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Nodular Pain of the Treated Nodule at Day 57</title>
        <description>After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening.</description>
        <time_frame>Baseline, Day 57</time_frame>
        <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500 0.60 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
          </group>
          <group group_id="O2">
            <title>AA4500 0.40 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
          </group>
          <group group_id="O3">
            <title>AA4500 0.25 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Nodular Pain of the Treated Nodule at Day 57</title>
          <description>After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening.</description>
          <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="22"/>
                <count group_id="O4" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="1.97"/>
                    <measurement group_id="O2" value="-1.6" spread="2.21"/>
                    <measurement group_id="O3" value="-1.7" spread="2.57"/>
                    <measurement group_id="O4" value="-0.5" spread="1.77"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.3135</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.7249</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.1573</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.1234</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Investigator Global Assessment of Improvement With Treatment</title>
        <description>Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.</description>
        <time_frame>Day 57</time_frame>
        <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500 0.60 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
          </group>
          <group group_id="O2">
            <title>AA4500 0.40 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
          </group>
          <group group_id="O3">
            <title>AA4500 0.25 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
          </group>
        </group_list>
        <measure>
          <title>Investigator Global Assessment of Improvement With Treatment</title>
          <description>Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.</description>
          <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="22"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" spread="0.84"/>
                    <measurement group_id="O2" value="1.7" spread="0.75"/>
                    <measurement group_id="O3" value="2.5" spread="1.10"/>
                    <measurement group_id="O4" value="3.0" spread="1.15"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0006</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0014</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0012</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.1298</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subject Satisfaction With Treatment</title>
        <description>Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied.</description>
        <time_frame>Day 57</time_frame>
        <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500 0.60 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
          </group>
          <group group_id="O2">
            <title>AA4500 0.40 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
          </group>
          <group group_id="O3">
            <title>AA4500 0.25 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Satisfaction With Treatment</title>
          <description>Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied.</description>
          <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="22"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="0.79"/>
                    <measurement group_id="O2" value="1.6" spread="0.85"/>
                    <measurement group_id="O3" value="2.3" spread="1.17"/>
                    <measurement group_id="O4" value="2.8" spread="1.34"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0048</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0034</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0079</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.3216</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Responder Analysis</title>
        <description>A composite responder is a subject who had an improved assessment [values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)] on the investigator global assessment and had a satisfied assessment [values of 1 (very satisfied) or 2 (quite satisfied)] on the subject assessment.</description>
        <time_frame>Day 57</time_frame>
        <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500 0.60 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
          </group>
          <group group_id="O2">
            <title>AA4500 0.40 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
          </group>
          <group group_id="O3">
            <title>AA4500 0.25 mg</title>
            <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Responder Analysis</title>
          <description>A composite responder is a subject who had an improved assessment [values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)] on the investigator global assessment and had a satisfied assessment [values of 1 (very satisfied) or 2 (quite satisfied)] on the subject assessment.</description>
          <population>Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="22"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responder: Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="12"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responder: No</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="10"/>
                    <measurement group_id="O4" value="10"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0065</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0349</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.0033</p_value>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>.3423</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from enrollment through the end of the study (Day 57).</time_frame>
      <desc>Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.</desc>
      <group_list>
        <group group_id="E1">
          <title>AA4500 0.60 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule</description>
        </group>
        <group group_id="E2">
          <title>AA4500 0.40 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule</description>
        </group>
        <group group_id="E3">
          <title>AA4500 0.25 mg</title>
          <description>Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.0</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="17" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Axillary pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site oedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection site swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Local swelling</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Tenderness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Injection related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Liver function test abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dupuytren's contracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Blood blister</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="17"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Coordinator</name_or_title>
      <organization>Endo Pharmaceuticals, Inc.</organization>
      <email>clinicalsite.inquiries@endo.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/NCT02193828
org study id: AUX-CC-750
nct id: NCT02193828
lead sponsor: 
has dmc: No
The objectives of this study are to assess the safety and effectiveness of AA4500 in treating
      palmar Dupuytren's disease nodules.
Approximately 13 sites in the United States and Australia, approximately 90 study subjects.

      After all pre-injection procedures are completed on day 1, eligible men and women will be
      randomized in a 1:1:1 ratio to dose group and then in a 4:1 ratio to treatment group. Study
      drug will be administered into a palmar nodule located on the selected hand.

      AA4500 (collagenase clostridium histolyticum) 3 doses (low, medium, and high) after
      reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium
      chloride). Each dose of study drug will be injected into the nodule. The injection will be
      administered in 3 different volumes according to randomization.

      Placebo after reconstitution with sterile diluent (0.3 mg/mL calcium chloride dihydrate in
      0.9% sodium chloride). Each dose of study drug will be injected into the nodule. The
      injection will be administered in 3 different volumes according to randomization.

      Follow up visits for the evaluation of safety and efficacy will be required for all subjects
      on days 8, 29, and 57.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements
time frame: Baseline, Day 57
description: Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.
measure: Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound
time frame: Baseline, Day 57
description: Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.
measure: Change From Baseline in Consistency of the Treated Nodules at Day 57
time frame: Baseline, Day 57
description: Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening.
measure: Percent Change From Baseline in Hardness of the Treated Nodule at Day 57
time frame: Baseline, Day 57
description: A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening.
measure: Change From Baseline in Nodular Pain of the Treated Nodule at Day 57
time frame: Baseline, Day 57
description: After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening.
measure: Investigator Global Assessment of Improvement With Treatment
time frame: Day 57
description: Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
measure: Subject Satisfaction With Treatment
time frame: Day 57
description: Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied.
measure: Composite Responder Analysis
time frame: Day 57
description: A composite responder is a subject who had an improved assessment [values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)] on the investigator global assessment and had a satisfied assessment [values of 1 (very satisfied) or 2 (quite satisfied)] on the subject assessment.
arm group label: AA4500 0.25 mg
arm group type: Experimental
description: Collagenase clostridium histolyticum, single 0.25 mg injection
arm group label: AA4500 0.40 mg
arm group type: Experimental
description: Collagenase clostridium histolyticum, single 0.40 mg injection
arm group label: AA4500 0.60 mg
arm group type: Experimental
description: Collagenase clostridium histolyticum, single 0.60 mg injection
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection
intervention type: Biological
intervention name: Collagenase clostridium histolyticum
description: Single injection into nodule
arm group label: AA4500 0.25 mg
arm group label: AA4500 0.40 mg
arm group label: AA4500 0.60 mg
other name: AA4500
other name: XIAFLEX
other name: XIAPEX
intervention type: Biological
intervention name: Placebo
description: Single injection into nodule
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Veronica Urdaneta, MD MPH
role: Study Director
affiliation: Endo Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: United States
responsible party type: Sponsor
mesh term: Dupuytren Contracture
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 