<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/NCT01685437</url>
  </required_header>
  <id_info>
    <org_study_id>AUX-CC-806</org_study_id>
    <nct_id>NCT01685437</nct_id>
  </id_info>
  <brief_title>A Phase 3, Open-label Study of the Safety and Effectiveness of AA4500 Administered Twice Per Treatment Cycle for up to Four Treatment Cycles (2 x 4) in Men With Peyronie's Disease</brief_title>
  <official_title>A Phase 3, Open-label Study of the Safety and Effectiveness of AA4500 Administered Twice Per Treatment Cycle for up to Four Treatment Cycles (2 x 4) in Men With Peyronie's Disease</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>
      This study is a Phase 3, open-label study of the safety and efficacy of AA4500 0.58 mg in&#xD;
      subjects with Peyronie's disease. Subjects will be screened for study eligibility within 21&#xD;
      days before the initial injection of study drug in the first treatment cycle. Enrollment will&#xD;
      include all subjects who meet the eligibility criteria and who received placebo and completed&#xD;
      one of the Auxilium-sponsored studies AUX-CC-803 or AUX-CC-804.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After the final injection of each treatment cycle, the investigator or qualified designee&#xD;
      (ie, qualified by license, education, and training to perform the study procedure according&#xD;
      to local, state, and country requirements) will model the plaque in an attempt to stretch or&#xD;
      elongate the plaque. If the subject's penile curvature is reduced to &lt;15° after the first,&#xD;
      second, or third cycle of injections or if the investigator determines further treatment is&#xD;
      not clinically indicated (eg, adverse events; allergic reaction), subsequent treatment cycles&#xD;
      will not be administered. Following the maximum of four treatment cycles, each subject will&#xD;
      be followed for additional safety and efficacy assessments on Days 168 (± 7 days) and 252 (±&#xD;
      7 days) (nominal weeks 24 and 36).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 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>Percentage Change From Baseline in Penile Curvature</measure>
    <time_frame>Baseline and Week 36</time_frame>
    <description>A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)</measure>
    <time_frame>Baseline and Week 36</time_frame>
    <description>Peyronie's disease bother score range 0 (no issue or not at all bothered) to 4 (extremely bothered) on 4 questions; total score range 0 to 16. A decrease in the change from baseline total score in the Peyronie's disease bother domain of the PDQ is indicated by a negative number.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ</measure>
    <time_frame>Baseline and Week 36</time_frame>
    <description>Peyronie's disease symptoms (physical and psychological) severity score range 0 (none) to 4 (very severe) on 6 questions; total score range 0 to 24. A decrease in the change from baseline total score in the Peyronie's disease symptoms domain of the PDQ is indicated by a negative number.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4</measure>
    <time_frame>Baseline and Week 36</time_frame>
    <description>Penile pain scale range 0 (no pain) to 10 (extreme pain) on 3 questions; total score range 0 to 30. A decrease in the change from baseline total score in the penile pain domain of the PDQ is indicated by a negative number. Subjects were required to have a penile pain score of 4 or greater at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A Responder Analysis Based on Subject Overall Global Assessment</measure>
    <time_frame>Week 36</time_frame>
    <description>Subject overall global assessment of Peyronie's disease score range -3 (much worse) to 3 (much improved). A score of 1 (improved in a small but important way), 2 (moderately improved), or 3 indicate a responder.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)</measure>
    <time_frame>Baseline and Week 36</time_frame>
    <description>Overall satisfaction domain of the IIEF score range 0 to 5 on 2 questions where higher scores indicate improved function or satisfaction; total score range 0 to 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Penile Plaque Consistency</measure>
    <time_frame>Baseline and Week 36</time_frame>
    <description>Penile plaque consistency score range 1 (non-palpable) to 5 (hard). A decrease in the change from baseline in penile plaque consistency is indicated by a negative number.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score</measure>
    <time_frame>Week 36</time_frame>
    <description>A composite responder is indicated by&#xD;
a percent reduction from baseline in penile curvature greater than or equal to the threshold, and&#xD;
a reduction from baseline in Peyronie's disease bother score greater than or equal to the threshold, or change in the overall sexual activity within the last 3 months to having vaginal intercourse from no vaginal intercourse at screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Penile Length</measure>
    <time_frame>Baseline and Week 36</time_frame>
    <description>A negative value represents a reduction in measurement from baseline.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">189</enrollment>
  <condition>Peyronie's Disease</condition>
  <arm_group>
    <arm_group_label>AA4500</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>collagenase clostridium histolyticum</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AA4500</intervention_name>
    <description>2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
    <arm_group_label>AA4500</arm_group_label>
    <other_name>Xiaflex</other_name>
    <other_name>Xiapex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        No subject should be enrolled until all eligibility criteria have been satisfied. Subjects&#xD;
        who completed their participation in Auxilium-sponsored studies AUX-CC-803 or AUX-CC-804&#xD;
        and received placebo in that study may enroll in this study provided they continue to meet&#xD;
        the eligibility requirements. To qualify for the study a subject must:&#xD;
&#xD;
          1. Have penile curvature of at least 30° in the dorsal, lateral, or dorsal/lateral plane&#xD;
             at screening. It must be possible to delineate the single plane of maximal curvature&#xD;
             for evaluation during the study&#xD;
&#xD;
          2. Be judged to be in good health, based upon the results of a medical history, physical&#xD;
             examination,and laboratory profile&#xD;
&#xD;
          3. Have participated in Study AUX-CC-803 or Study AUX-CC-804, received placebo in that&#xD;
             study,and completed that study&#xD;
&#xD;
          4. Voluntarily sign and date an informed consent agreement approved by the Institutional&#xD;
             Review Board/Independent Ethics Committee (IRB/IEC). The subject must also sign an&#xD;
             authorization form to allow disclosure of his protected health information (PHI). The&#xD;
             PHI authorization form and informed consent form may be an integrated form or may be&#xD;
             separate forms depending on the institution&#xD;
&#xD;
          5. Be able to read, complete and understand the various rating instruments in English.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A subject will be excluded from study participation if he:&#xD;
&#xD;
          1. Has a penile curvature of less than 30° or greater than 90° at the screening visit&#xD;
&#xD;
          2. Has any of the following conditions:&#xD;
&#xD;
               -  Chordee in the presence or absence of hypospadias&#xD;
&#xD;
               -  Thrombosis of the dorsal penile artery and/or vein&#xD;
&#xD;
               -  Infiltration by a benign or malignant mass resulting in penile curvature&#xD;
&#xD;
               -  Infiltration by an infectious agent, such as lymphogranuloma venereum&#xD;
&#xD;
               -  Ventral curvature from any cause&#xD;
&#xD;
               -  Presence of an active sexually transmitted disease&#xD;
&#xD;
               -  Known active hepatitis B or C&#xD;
&#xD;
               -  Known immune deficiency disease or be positive for human immunodeficiency virus&#xD;
                  (HIV)&#xD;
&#xD;
          3. Has previously undergone surgery for Peyronie's disease&#xD;
&#xD;
          4. Fails to have an erection which in the opinion of the investigator is sufficient to&#xD;
             accurately measure the subject's penile deformity after administration of&#xD;
             prostaglandin E1 or trimix or another suitable injectable pharmacologic stimulant&#xD;
             according to the standard practice at the investigator's institution&#xD;
&#xD;
          5. Has a calcified plaque as evident by appropriate radiographic evaluation, penile x-ray&#xD;
             or penile ultrasound that would prevent proper injection of study medication.&#xD;
             Non-contiguous stippling of calcium is acceptable for inclusion provided the calcium&#xD;
             deposit does not interfere with the injection of AA4500 into the plaque&#xD;
&#xD;
          6. Has an isolated hourglass deformity of the penis&#xD;
&#xD;
          7. Has the plaque causing curvature of the penis located proximal to the base of the&#xD;
             penis, so that the injection of the local anesthetic would interfere with the&#xD;
             injection of AA4500 into the plaque&#xD;
&#xD;
          8. Has previously received alternative medical therapies for Peyronie's disease&#xD;
             administered by the intralesional route (including, but not limited to, steroids,&#xD;
             verapamil, and the naturally occurring low molecular weight protein, interferon-α2b)&#xD;
             within 3 months before the first dose of study drug or plans to use any of these&#xD;
             medical therapies at any time during the study&#xD;
&#xD;
          9. Has received alternative medical therapies for Peyronie's disease administered by the&#xD;
             oral (including, but not limited to, vitamin E [&gt;500 U], potassium aminobenzoate&#xD;
             [Potaba], tamoxifen, colchicine, and pentoxifylline, ,) or topical routes (including,&#xD;
             but not limited to, verapamil applied as a cream) within 3 months before the first&#xD;
             dose of study drug or plans to use any of these medical therapies at any time during&#xD;
             the study&#xD;
&#xD;
         10. Has had extracorporeal shock wave therapy (ESWT) for the correction of Peyronie's&#xD;
             disease within the 6-month period before screening or plans to have ESWT at any time&#xD;
             during the study&#xD;
&#xD;
         11. Has used any mechanical type device for correction of Peyronie's disease within the&#xD;
             2-week period before screening or plans to use any these devices at any time during&#xD;
             the study&#xD;
&#xD;
         12. Has used a mechanical device to induce a passive erection within the 2-week period&#xD;
             before screening or plans to use any of these devices at any time during the study&#xD;
&#xD;
         13. Has significant erectile dysfunction that has failed to respond to oral treatment with&#xD;
             phosphodiesterase type 5 (PDE5) inhibitors&#xD;
&#xD;
         14. Has a penile Duplex Doppler ultrasound evaluation at screening that shows compromised&#xD;
             penile hemodynamics that in the opinion of the investigator is clinically significant&#xD;
&#xD;
         15. Has uncontrolled hypertension, as determined by the investigator&#xD;
&#xD;
         16. Has a known recent history of stroke, bleeding, or other significant medical&#xD;
             condition, which in the investigator's opinion would make the subject unsuitable for&#xD;
             enrollment in the study&#xD;
&#xD;
         17. Has received an investigational drug or treatment within 30 days before the first dose&#xD;
             of study drug, except for placebo in Studies AUX-CC-803 or AUX-CC-804&#xD;
&#xD;
         18. Has a known systemic allergy to collagenase or any other excipient of AA4500&#xD;
&#xD;
         19. Has a known allergy to any concomitant medication required as per the protocol&#xD;
&#xD;
         20. Has received anticoagulant medication (except for ≤ 150 mg aspirin daily) during the 7&#xD;
             days before each dose of study drug&#xD;
&#xD;
         21. Has received any collagenase treatments within 30 days of the first dose of study drug&#xD;
&#xD;
         22. Has, at any time, received AA4500 for the treatment of Peyronie's disease&#xD;
&#xD;
         23. Is unwilling or unable to cooperate with the requirements of the study including&#xD;
             completion of all scheduled study visits&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gregory Kaufman, MD</last_name>
    <role>Study Director</role>
    <affiliation>Auxilium Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <results_first_submitted>February 4, 2015</results_first_submitted>
  <results_first_submitted_qc>March 24, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 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>Peyronie's disease, penile plaque, penile curvature</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Penile Induration</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>AA4500</title>
          <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="189"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="158"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </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>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unable to make visits due to work</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>AA4500</title>
          <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="189"/>
          </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="134"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                  </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="60.2" spread="7.32"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="184"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="186"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change From Baseline in Penile Curvature</title>
        <description>A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.</description>
        <time_frame>Baseline and Week 36</time_frame>
        <population>Efficacy is based on modified intent-to-treat (mITT) population.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline in Penile Curvature</title>
          <description>A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.</description>
          <population>Efficacy is based on modified intent-to-treat (mITT) population.</population>
          <units>percentage of curvature 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="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-36.3" spread="30.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)</title>
        <description>Peyronie's disease bother score range 0 (no issue or not at all bothered) to 4 (extremely bothered) on 4 questions; total score range 0 to 16. A decrease in the change from baseline total score in the Peyronie's disease bother domain of the PDQ is indicated by a negative number.</description>
        <time_frame>Baseline and Week 36</time_frame>
        <population>Efficacy is based on the mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)</title>
          <description>Peyronie's disease bother score range 0 (no issue or not at all bothered) to 4 (extremely bothered) on 4 questions; total score range 0 to 16. A decrease in the change from baseline total score in the Peyronie's disease bother domain of the PDQ is indicated by a negative number.</description>
          <population>Efficacy is based on the mITT population.</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="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="3.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ</title>
        <description>Peyronie's disease symptoms (physical and psychological) severity score range 0 (none) to 4 (very severe) on 6 questions; total score range 0 to 24. A decrease in the change from baseline total score in the Peyronie's disease symptoms domain of the PDQ is indicated by a negative number.</description>
        <time_frame>Baseline and Week 36</time_frame>
        <population>Efficacy is based on the mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ</title>
          <description>Peyronie's disease symptoms (physical and psychological) severity score range 0 (none) to 4 (very severe) on 6 questions; total score range 0 to 24. A decrease in the change from baseline total score in the Peyronie's disease symptoms domain of the PDQ is indicated by a negative number.</description>
          <population>Efficacy is based on the mITT population.</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="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.9" spread="4.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4</title>
        <description>Penile pain scale range 0 (no pain) to 10 (extreme pain) on 3 questions; total score range 0 to 30. A decrease in the change from baseline total score in the penile pain domain of the PDQ is indicated by a negative number. Subjects were required to have a penile pain score of 4 or greater at baseline.</description>
        <time_frame>Baseline and Week 36</time_frame>
        <population>Efficacy is based on the mITT population; this population only includes those subjects in the mITT population with a baseline penile pain score of 4 or greater.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4</title>
          <description>Penile pain scale range 0 (no pain) to 10 (extreme pain) on 3 questions; total score range 0 to 30. A decrease in the change from baseline total score in the penile pain domain of the PDQ is indicated by a negative number. Subjects were required to have a penile pain score of 4 or greater at baseline.</description>
          <population>Efficacy is based on the mITT population; this population only includes those subjects in the mITT population with a baseline penile pain score of 4 or greater.</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="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.5" spread="4.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>A Responder Analysis Based on Subject Overall Global Assessment</title>
        <description>Subject overall global assessment of Peyronie's disease score range -3 (much worse) to 3 (much improved). A score of 1 (improved in a small but important way), 2 (moderately improved), or 3 indicate a responder.</description>
        <time_frame>Week 36</time_frame>
        <population>Efficacy is based on the mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>A Responder Analysis Based on Subject Overall Global Assessment</title>
          <description>Subject overall global assessment of Peyronie's disease score range -3 (much worse) to 3 (much improved). A score of 1 (improved in a small but important way), 2 (moderately improved), or 3 indicate a responder.</description>
          <population>Efficacy is based on the mITT population.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responder Status - No</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Responder Status - Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)</title>
        <description>Overall satisfaction domain of the IIEF score range 0 to 5 on 2 questions where higher scores indicate improved function or satisfaction; total score range 0 to 10.</description>
        <time_frame>Baseline and Week 36</time_frame>
        <population>Efficacy is based on the mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)</title>
          <description>Overall satisfaction domain of the IIEF score range 0 to 5 on 2 questions where higher scores indicate improved function or satisfaction; total score range 0 to 10.</description>
          <population>Efficacy is based on the mITT population.</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="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="2.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Penile Plaque Consistency</title>
        <description>Penile plaque consistency score range 1 (non-palpable) to 5 (hard). A decrease in the change from baseline in penile plaque consistency is indicated by a negative number.</description>
        <time_frame>Baseline and Week 36</time_frame>
        <population>Efficacy is based on the mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Penile Plaque Consistency</title>
          <description>Penile plaque consistency score range 1 (non-palpable) to 5 (hard). A decrease in the change from baseline in penile plaque consistency is indicated by a negative number.</description>
          <population>Efficacy is based on the mITT population.</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="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score</title>
        <description>A composite responder is indicated by&#xD;
a percent reduction from baseline in penile curvature greater than or equal to the threshold, and&#xD;
a reduction from baseline in Peyronie's disease bother score greater than or equal to the threshold, or change in the overall sexual activity within the last 3 months to having vaginal intercourse from no vaginal intercourse at screening.</description>
        <time_frame>Week 36</time_frame>
        <population>Composite responder analysis is based on the intent-to-treat (ITT) population.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score</title>
          <description>A composite responder is indicated by&#xD;
a percent reduction from baseline in penile curvature greater than or equal to the threshold, and&#xD;
a reduction from baseline in Peyronie's disease bother score greater than or equal to the threshold, or change in the overall sexual activity within the last 3 months to having vaginal intercourse from no vaginal intercourse at screening.</description>
          <population>Composite responder analysis is based on the intent-to-treat (ITT) population.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="189"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Penile Length</title>
        <description>A negative value represents a reduction in measurement from baseline.</description>
        <time_frame>Baseline and Week 36</time_frame>
        <population>Efficacy is based on the mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>AA4500</title>
            <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Penile Length</title>
          <description>A negative value represents a reduction in measurement from baseline.</description>
          <population>Efficacy is based on the mITT population.</population>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="1.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>AA4500</title>
          <description>collagenase clostridium histolyticum&#xD;
AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (13.1)</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="3" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Caecitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Acoustic neuroma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Calculus ureteric</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (13.1)</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="178" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site haematoma</sub_title>
                <counts group_id="E1" events="66" subjects_affected="35" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="50" subjects_affected="32" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Injection site haemorrhage</sub_title>
                <counts group_id="E1" events="56" subjects_affected="21" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Injection site swelling</sub_title>
                <counts group_id="E1" events="27" subjects_affected="20" subjects_at_risk="189"/>
              </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="20" subjects_affected="17" subjects_at_risk="189"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Penile haematoma</sub_title>
                <counts group_id="E1" events="271" subjects_affected="114" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Penile pain</sub_title>
                <counts group_id="E1" events="121" subjects_affected="64" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Penile swelling</sub_title>
                <counts group_id="E1" events="99" subjects_affected="57" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Penile oedema</sub_title>
                <counts group_id="E1" events="91" subjects_affected="46" subjects_at_risk="189"/>
              </event>
              <event>
                <sub_title>Penile haemorrhage</sub_title>
                <counts group_id="E1" events="73" subjects_affected="39" subjects_at_risk="189"/>
              </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/NCT01685437
org study id: AUX-CC-806
nct id: NCT01685437
lead sponsor: 
has dmc: No
This study is a Phase 3, open-label study of the safety and efficacy of AA4500 0.58 mg in
      subjects with Peyronie's disease. Subjects will be screened for study eligibility within 21
      days before the initial injection of study drug in the first treatment cycle. Enrollment will
      include all subjects who meet the eligibility criteria and who received placebo and completed
      one of the Auxilium-sponsored studies AUX-CC-803 or AUX-CC-804.
After the final injection of each treatment cycle, the investigator or qualified designee
      (ie, qualified by license, education, and training to perform the study procedure according
      to local, state, and country requirements) will model the plaque in an attempt to stretch or
      elongate the plaque. If the subject's penile curvature is reduced to <15° after the first,
      second, or third cycle of injections or if the investigator determines further treatment is
      not clinically indicated (eg, adverse events; allergic reaction), subsequent treatment cycles
      will not be administered. Following the maximum of four treatment cycles, each subject will
      be followed for additional safety and efficacy assessments on Days 168 (± 7 days) and 252 (±
      7 days) (nominal weeks 24 and 36).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage Change From Baseline in Penile Curvature
time frame: Baseline and Week 36
description: A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.
measure: Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)
time frame: Baseline and Week 36
description: Peyronie's disease bother score range 0 (no issue or not at all bothered) to 4 (extremely bothered) on 4 questions; total score range 0 to 16. A decrease in the change from baseline total score in the Peyronie's disease bother domain of the PDQ is indicated by a negative number.
measure: Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ
time frame: Baseline and Week 36
description: Peyronie's disease symptoms (physical and psychological) severity score range 0 (none) to 4 (very severe) on 6 questions; total score range 0 to 24. A decrease in the change from baseline total score in the Peyronie's disease symptoms domain of the PDQ is indicated by a negative number.
measure: Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4
time frame: Baseline and Week 36
description: Penile pain scale range 0 (no pain) to 10 (extreme pain) on 3 questions; total score range 0 to 30. A decrease in the change from baseline total score in the penile pain domain of the PDQ is indicated by a negative number. Subjects were required to have a penile pain score of 4 or greater at baseline.
measure: A Responder Analysis Based on Subject Overall Global Assessment
time frame: Week 36
description: Subject overall global assessment of Peyronie's disease score range -3 (much worse) to 3 (much improved). A score of 1 (improved in a small but important way), 2 (moderately improved), or 3 indicate a responder.
measure: Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)
time frame: Baseline and Week 36
description: Overall satisfaction domain of the IIEF score range 0 to 5 on 2 questions where higher scores indicate improved function or satisfaction; total score range 0 to 10.
measure: Change From Baseline in Penile Plaque Consistency
time frame: Baseline and Week 36
description: Penile plaque consistency score range 1 (non-palpable) to 5 (hard). A decrease in the change from baseline in penile plaque consistency is indicated by a negative number.
measure: A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score
time frame: Week 36
description: A composite responder is indicated by
a percent reduction from baseline in penile curvature greater than or equal to the threshold, and
a reduction from baseline in Peyronie's disease bother score greater than or equal to the threshold, or change in the overall sexual activity within the last 3 months to having vaginal intercourse from no vaginal intercourse at screening.
measure: Change From Baseline in Penile Length
time frame: Baseline and Week 36
description: A negative value represents a reduction in measurement from baseline.
arm group label: AA4500
arm group type: Experimental
description: collagenase clostridium histolyticum
intervention type: Biological
intervention name: AA4500
description: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
arm group label: AA4500
other name: Xiaflex
other name: Xiapex
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gregory Kaufman, MD
role: Study Director
affiliation: Auxilium Pharmaceuticals, Inc.
responsible party type: Sponsor
mesh term: Penile Induration
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 