<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/NCT01674634</url>
  </required_header>
  <id_info>
    <org_study_id>AUX-CC-867</org_study_id>
    <nct_id>NCT01674634</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures</brief_title>
  <official_title>A Phase 3b Open-label, Historically-controlled Study to Assess the Safety and Efficacy of Two Concurrent Injections of AA4500 in Adult Subjects With Multiple Dupuytren's Contractures With Palpable Cords</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 primary objective of this study is to assess the safety of two concurrent injections of&#xD;
      AA4500 into the same hand in subjects with multiple Dupuytren's contractures with palpable&#xD;
      cords followed 24 to 72 hours later by a finger extension procedure and compare the rate of&#xD;
      occurrence of targeted serious adverse events (tendon rupture/ligament injury and&#xD;
      anaphylaxis) to historical rates of the same in clinical studies and post-marketing&#xD;
      commercial use.&#xD;
&#xD;
      The secondary objective is to evaluate the efficacy of two concurrent injections of AA4500.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methodology/Study Design: After all pre-injection procedures are completed on Day 1, eligible&#xD;
      men and women will receive two concurrent injections AA4500 (AA4500/AA4500) into cord(s)&#xD;
      affecting MP and/or PIP joints on the same or different fingers in the selected hand. A&#xD;
      finger extension procedure to facilitate cord disruption will be performed (after&#xD;
      administration of local anesthesia, if needed) 24 to 72 hours after injection in those&#xD;
      subjects who do not have spontaneous disruption of their cord(s).&#xD;
&#xD;
      Follow up visits for the evaluation of safety and efficacy will be required for all subjects&#xD;
      24 to 72 hours after injection, and on Days 15, 31, and 61.&#xD;
&#xD;
      Upon completion of the day 61 follow-up visit (end of study visit), subjects who require&#xD;
      additional treatment in the treated hand may receive up to three additional injections of&#xD;
      AA4500 according to the XIAFLEX package insert. Subjects may receive up to a total of five&#xD;
      injections and individual cords may receive up to a total of three injections. Subjects who&#xD;
      require additional treatment will be followed for safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">July 2013</completion_date>
  <primary_completion_date type="Actual">July 2013</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change From Baseline in Total Fixed Flexion</measure>
    <time_frame>Baseline, Day 31</time_frame>
    <description>Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Total Range of Motion</measure>
    <time_frame>Baseline, Day 31</time_frame>
    <description>The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Success</measure>
    <time_frame>Within 30 days</time_frame>
    <description>Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Improvement</measure>
    <time_frame>Within 30 days</time_frame>
    <description>Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject Assessment of Satisfaction With Treatment at Day 31</measure>
    <time_frame>Day 31</time_frame>
    <description>Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject Assessment of Satisfaction With Treatment at Day 61</measure>
    <time_frame>Day 61</time_frame>
    <description>Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator Assessment of Improvement With Treatment at Day 31</measure>
    <time_frame>Day 31</time_frame>
    <description>Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 31 follow-up visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator Assessment of Improvement With Treatment at Day 61</measure>
    <time_frame>Day 61</time_frame>
    <description>Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 61 follow-up visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31</measure>
    <time_frame>Baseline, Day 31</time_frame>
    <description>The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61</measure>
    <time_frame>Baseline, Day 61</time_frame>
    <description>The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">715</enrollment>
  <condition>Dupuytren's Contracture</condition>
  <arm_group>
    <arm_group_label>XIAFLEX / XIAPEX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AA4500 (collagenase clostridium histolyticum)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>XIAFLEX / XIAPEX</intervention_name>
    <description>injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride])</description>
    <arm_group_label>XIAFLEX / XIAPEX</arm_group_label>
    <other_name>AA4500 (collagenase clostridium histolyticum)</other_name>
  </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 2 fixed-flexion contractures&#xD;
             on the same hand that are ≥ 20º in PIP and/or MP joints in fingers, other than the&#xD;
             thumbs, which are caused by palpable cord(s) suitable for treatment&#xD;
&#xD;
          4. Have a positive &quot;table top test&quot; defined as the inability to simultaneously place the&#xD;
             affected finger(s) and palm flat against a table top&#xD;
&#xD;
          5. 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;
          6. Be able to comply with the study visit schedule as specified in the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A subject will be excluded from study participation if he/she:&#xD;
&#xD;
          1. Received surgery (fasciectomy or surgical fasciotomy) and/or needle&#xD;
             aponeurotomy/fasciotomy on the selected joints to be treated within 6 months before&#xD;
             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. 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>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Veronica Urdaneta, MD, MPPH</last_name>
    <role>Study Director</role>
    <affiliation>Endo Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HOPE Research Institute</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85018</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>Torrey Pines Medical Group</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</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>The Hand and Upper Extremity Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rockford Orthopedic Associates</name>
      <address>
        <city>Rockford</city>
        <state>Illinois</state>
        <zip>61107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The 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>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christine M. Kleinert Institute for Hand and Microsurgery, Inc.</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lake Cumberland Rheumatology</name>
      <address>
        <city>Somerset</city>
        <state>Kentucky</state>
        <zip>42503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TRIA Orthopedic Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55431</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Missoula Bone and Joint</name>
      <address>
        <city>Missoula</city>
        <state>Montana</state>
        <zip>59808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nevada Orthopedic and Spine Center</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Jersey Hand Surgery</name>
      <address>
        <city>Eatontown</city>
        <state>New Jersey</state>
        <zip>07724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Stony Brook</name>
      <address>
        <city>Setauket</city>
        <state>New York</state>
        <zip>11733</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNC School of Medicine</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</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>Health Research Institute</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Neurosurgical and Orthopedic Care and Research</name>
      <address>
        <city>Bend</city>
        <state>Oregon</state>
        <zip>97701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hand Microsurgery &amp; Reconstructive Orthopaedics</name>
      <address>
        <city>Erie</city>
        <state>Pennsylvania</state>
        <zip>16507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alpha Clinical Research, LLC</name>
      <address>
        <city>Clarksville</city>
        <state>Tennessee</state>
        <zip>37043</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accurate Clinical Research, Inc.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Arthritis Clinic of Northern Virginia, PA</name>
      <address>
        <city>Arlington</city>
        <state>Virginia</state>
        <zip>22205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <results_first_submitted>February 4, 2015</results_first_submitted>
  <results_first_submitted_qc>February 4, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 20, 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>XIAFLEX</keyword>
  <keyword>XIAPEX</keyword>
  <keyword>Dupuytren's disease</keyword>
  <keyword>contracture</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dupuytren Contracture</mesh_term>
    <mesh_term>Contracture</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>XIAFLEX/XIAPEX</title>
          <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="715"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="709"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>XIAFLEX/XIAPEX</title>
          <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="715"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="348"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="367"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.0" spread="9.26"/>
                  </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="99"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="616"/>
                  </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="278"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="196"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>New Zealand</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sweden</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change From Baseline in Total Fixed Flexion</title>
        <description>Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.</description>
        <time_frame>Baseline, Day 31</time_frame>
        <population>Efficacy analysis was based on the modified intent-to-treat (mITT) population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX</title>
            <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Total Fixed Flexion</title>
          <description>Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.</description>
          <population>Efficacy analysis was based on the modified intent-to-treat (mITT) population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
          <units>percentage of contracture change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Treated Joint Pairs</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joint Pairs</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="724"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.41" spread="24.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Total Range of Motion</title>
        <description>The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM.</description>
        <time_frame>Baseline, Day 31</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX</title>
            <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total Range of Motion</title>
          <description>The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM.</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <units_analyzed>treated joint pairs</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>treated joint pairs</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="724"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.6" lower_limit="64.3" upper_limit="68.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Success</title>
        <description>Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection</description>
        <time_frame>Within 30 days</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX MP Joint</title>
            <description>AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the metacarpophalangeal (MP) joint cord</description>
          </group>
          <group group_id="O2">
            <title>XIAFLEX/XIAPEX PIP Joint</title>
            <description>AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the proximal interphalangeal (PIP) joint cord</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Success</title>
          <description>Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type.</population>
          <units>Joints</units>
          <param>Number</param>
          <units_analyzed>Treated Joints</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
                <count group_id="O2" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joints</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="896"/>
                <count group_id="O2" value="552"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="317"/>
                    <measurement group_id="O2" value="394"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="579"/>
                    <measurement group_id="O2" value="158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Improvement</title>
        <description>Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection</description>
        <time_frame>Within 30 days</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX MP Joint</title>
            <description>AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the MP joint cord</description>
          </group>
          <group group_id="O2">
            <title>XIAFLEX/XIAPEX PIP Joint</title>
            <description>AA4500 (collagenase clostridium histolyticum); 0.58 mg injection in the PIP joint cord</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Improvement</title>
          <description>Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. This assessment is based on individual treated joints by joint type.</population>
          <units>Joints</units>
          <param>Number</param>
          <units_analyzed>Treated Joints</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
                <count group_id="O2" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joints</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="896"/>
                <count group_id="O2" value="552"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96"/>
                    <measurement group_id="O2" value="157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="800"/>
                    <measurement group_id="O2" value="395"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subject Assessment of Satisfaction With Treatment at Day 31</title>
        <description>Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit</description>
        <time_frame>Day 31</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX</title>
            <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Assessment of Satisfaction With Treatment at Day 31</title>
          <description>Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
          <units>Joint Pairs</units>
          <param>Number</param>
          <units_analyzed>Treated Joint Pairs</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joint Pairs</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="724"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very satisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="461"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quite satisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="198"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neither satisfied nor dissatisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quite dissatisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very dissatisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not done</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subject Assessment of Satisfaction With Treatment at Day 61</title>
        <description>Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit</description>
        <time_frame>Day 61</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX</title>
            <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Assessment of Satisfaction With Treatment at Day 61</title>
          <description>Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
          <units>Joint Pairs</units>
          <param>Number</param>
          <units_analyzed>Treated Joint Pairs</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joint Pairs</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="724"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very satisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="496"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quite satisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="167"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neither satisfied nor dissatisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quite dissatisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very dissatisfied</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not done</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Investigator Assessment of Improvement With Treatment at Day 31</title>
        <description>Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 31 follow-up visit.</description>
        <time_frame>Day 31</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX</title>
            <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
          </group>
        </group_list>
        <measure>
          <title>Investigator Assessment of Improvement With Treatment at Day 31</title>
          <description>Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 31 follow-up visit.</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
          <units>Joint Pairs</units>
          <param>Number</param>
          <units_analyzed>Treated Joint Pairs</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joint Pairs</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="724"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="375"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="271"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minimally improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minimally worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not done</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Investigator Assessment of Improvement With Treatment at Day 61</title>
        <description>Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 61 follow-up visit.</description>
        <time_frame>Day 61</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX</title>
            <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
          </group>
        </group_list>
        <measure>
          <title>Investigator Assessment of Improvement With Treatment at Day 61</title>
          <description>Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 61 follow-up visit.</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
          <units>Joint Pairs</units>
          <param>Number</param>
          <units_analyzed>Treated Joint Pairs</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joint Pairs</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="724"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="382"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="263"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minimally improved</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Minimally worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very much worse</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not done</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31</title>
        <description>The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.</description>
        <time_frame>Baseline, Day 31</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX</title>
            <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31</title>
          <description>The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Treated Joint Pairs</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joint Pairs</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="724"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.3" spread="9.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61</title>
        <description>The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.</description>
        <time_frame>Baseline, Day 61</time_frame>
        <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
        <group_list>
          <group group_id="O1">
            <title>XIAFLEX/XIAPEX</title>
            <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61</title>
          <description>The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.</description>
          <population>Efficacy analysis was based on the mITT population; all enrolled subjects who received both AA4500 injections and had a post-injection efficacy measure. Ten subjects were granted special re-enrollment and had an additional joint pair treated on the contralateral hand. Assessment is based on simultaneously treated joint pairs.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Treated Joint Pairs</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="714"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Treated Joint Pairs</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="724"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.3" spread="9.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>XIAFLEX/XIAPEX</title>
          <description>AA4500 (collagenase clostridium histolyticum): 2 concurrent 0.58 mg injections (1 injection per joint) in the same hand</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lymphangitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Anal abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <description>Left lower leg</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Feeding tube complication</sub_title>
                <description>PEG feeding tube obstruction</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <description>Bleeding left hand post procedure</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <description>Upgraded to an SAE by the sponsor</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Spinal column stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Myelopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Emphysema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Arteriosclerosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (15.1)</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="680" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" events="102" subjects_affected="92" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="626" subjects_affected="552" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="109" subjects_affected="102" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Injection site haematoma</sub_title>
                <counts group_id="E1" events="61" subjects_affected="60" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Axillary pain</sub_title>
                <counts group_id="E1" events="53" subjects_affected="51" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>injection site haemorrhage</sub_title>
                <description>injection site ecchymosis</description>
                <counts group_id="E1" events="45" subjects_affected="45" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Injection site swelling</sub_title>
                <counts group_id="E1" events="42" subjects_affected="42" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="513" subjects_affected="420" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" events="192" subjects_affected="184" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="431" subjects_affected="361" subjects_at_risk="715"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="121" subjects_affected="107" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Blood blister</sub_title>
                <counts group_id="E1" events="98" subjects_affected="89" subjects_at_risk="715"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" events="39" subjects_affected="37" subjects_at_risk="715"/>
              </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/NCT01674634
org study id: AUX-CC-867
nct id: NCT01674634
lead sponsor: 
has dmc: No
The primary objective of this study is to assess the safety of two concurrent injections of
      AA4500 into the same hand in subjects with multiple Dupuytren's contractures with palpable
      cords followed 24 to 72 hours later by a finger extension procedure and compare the rate of
      occurrence of targeted serious adverse events (tendon rupture/ligament injury and
      anaphylaxis) to historical rates of the same in clinical studies and post-marketing
      commercial use.

      The secondary objective is to evaluate the efficacy of two concurrent injections of AA4500.
Methodology/Study Design: After all pre-injection procedures are completed on Day 1, eligible
      men and women will receive two concurrent injections AA4500 (AA4500/AA4500) into cord(s)
      affecting MP and/or PIP joints on the same or different fingers in the selected hand. A
      finger extension procedure to facilitate cord disruption will be performed (after
      administration of local anesthesia, if needed) 24 to 72 hours after injection in those
      subjects who do not have spontaneous disruption of their cord(s).

      Follow up visits for the evaluation of safety and efficacy will be required for all subjects
      24 to 72 hours after injection, and on Days 15, 31, and 61.

      Upon completion of the day 61 follow-up visit (end of study visit), subjects who require
      additional treatment in the treated hand may receive up to three additional injections of
      AA4500 according to the XIAFLEX package insert. Subjects may receive up to a total of five
      injections and individual cords may receive up to a total of three injections. Subjects who
      require additional treatment will be followed for safety.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent Change From Baseline in Total Fixed Flexion
time frame: Baseline, Day 31
description: Percent change from baseline in total fixed flexion = 100 * (baseline total FFC - day 31 total FFC)/baseline total FFC, where total fixed flexion is defined as the sum of the fixed flexion contracture (FCC) of the 2 joints receiving treatment. Positive percent change from baseline indicates improvement.
measure: Change From Baseline in Total Range of Motion
time frame: Baseline, Day 31
description: The total range of motion (ROM) is the sum of the range of motion measurements of the 2 treated joints. ROM is defined as difference between full flexion angle and full extension expressed in degrees. A positive change from baseline indicates increased (improved) ROM.
measure: Clinical Success
time frame: Within 30 days
description: Clinical success is defined as reduction of FFC of a treated joint to within 0-5 degrees of normal within 30 days of injection
measure: Clinical Improvement
time frame: Within 30 days
description: Clinical improvement is defined as a reduction of FFC by 50% or greater of the baseline value within 30 days of injection
measure: Subject Assessment of Satisfaction With Treatment at Day 31
time frame: Day 31
description: Subject's were asked to rate satisfaction with treatment at the day 31 follow-up visit
measure: Subject Assessment of Satisfaction With Treatment at Day 61
time frame: Day 61
description: Subject's were asked to rate satisfaction with treatment at the day 61 follow-up visit
measure: Investigator Assessment of Improvement With Treatment at Day 31
time frame: Day 31
description: Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 31 follow-up visit.
measure: Investigator Assessment of Improvement With Treatment at Day 61
time frame: Day 61
description: Investigator's determined the degree of improvement in the severity of the subject's treated finger(s) compared with screening at the day 61 follow-up visit.
measure: Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 31
time frame: Baseline, Day 31
description: The Unité Rhumatologique des Affections de la Main (URAM) scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.
measure: Change From Baseline for Unité Rhumatologique Des Affections de la Main Scale at Day 61
time frame: Baseline, Day 61
description: The URAM scale is a patient-reported functional 9-item scale (total score 0-45) developed and validated to assess functional outcome of patients suffering from Dupuytren's disease with higher scores indicating greater difficulty using the hand.The estimated clinically important change of the URAM scale is 2.9 points. A decrease in total URAM score indicates improvement in hand function.
arm group label: XIAFLEX / XIAPEX
arm group type: Experimental
description: AA4500 (collagenase clostridium histolyticum)
intervention type: Biological
intervention name: XIAFLEX / XIAPEX
description: injection (0.58 mg after reconstitution with sterile diluent [0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride])
arm group label: XIAFLEX / XIAPEX
other name: AA4500 (collagenase clostridium histolyticum)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Veronica Urdaneta, MD, MPPH
role: Study Director
affiliation: Endo Pharmaceuticals
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country: United States
responsible party type: Sponsor
mesh term: Dupuytren Contracture
mesh term: Contracture
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 