<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/NCT02993926</url>
  </required_header>
  <id_info>
    <org_study_id>Leuprorelin-5001</org_study_id>
    <nct_id>NCT02993926</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Safety and Efficacy of Enantone (Leuprorelin) in Central Precocious Puberty (CPP) Among Chinese Participants</brief_title>
  <official_title>An Observational, Retrospective Study to Evaluate the Long Term Safety and Effectiveness of Leuprorelin in the Treatment of Central Precocious Puberty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the long-term safety and efficacy of Enantone in the&#xD;
      treatment of CPP in Chinese participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being evaluated in this study is called Enantone (leuprorelin). Enantone is used to&#xD;
      treat children who have CPP. This study will look at long term safety and efficacy of&#xD;
      leuprorelin in the treatment of Chinese participants with CPP.&#xD;
&#xD;
      The study will enroll approximately 300 participants.&#xD;
&#xD;
      All participants who have received leuprorelin 30 mcg/kg to &lt;90 mcg/kg or 90 mcg/kg to 180&#xD;
      mcg/kg per body weight, injection, subcutaneously, every 4 weeks up to at least 9 continuous&#xD;
      months during the index period from September 1st 1998 to September 30th 2018 will be&#xD;
      observed.&#xD;
&#xD;
      This multi-center trial will be conducted in China. Data will be collected over period of 20&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 24, 2017</start_date>
  <completion_date type="Actual">September 30, 2018</completion_date>
  <primary_completion_date type="Actual">September 30, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) During Enantone Treatment Phase</measure>
    <time_frame>During treatment with and up to 30 days post last dose of Enantone (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months)</time_frame>
    <description>A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With at Least One Treatment Emergent Adverse (TEAE) and Serious Adverse Event (SAE) During Follow-up Phase</measure>
    <time_frame>Mean duration of follow-up=8.75 months (range: 1.9-29.5 months) for No longer treated for CPP group; 10.80 months (range: 2.8-20.5 months) for Treated with Non-Enantone GnRHa group after treatment with Enantone (while on another GnRHa)</time_frame>
    <description>A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Enantone Treatment Phase</measure>
    <time_frame>The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months</time_frame>
    <description>Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Follow-Up Phase</measure>
    <time_frame>No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone</time_frame>
    <description>Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase</measure>
    <time_frame>The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months</time_frame>
    <description>The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase</measure>
    <time_frame>No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone</time_frame>
    <description>The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase</measure>
    <time_frame>The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months</time_frame>
    <description>Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase</measure>
    <time_frame>No longer treated for CPP group-Month: 27 (766-855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group-Month 21 (586-675 days) post last dose of Enantone</time_frame>
    <description>Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Enantone Treatment Phase</measure>
    <time_frame>The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months</time_frame>
    <description>Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Follow-up Phase</measure>
    <time_frame>No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 18 (496-585 days) post last dose of Enantone</time_frame>
    <description>Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">108</enrollment>
  <condition>Central Precocious Puberty</condition>
  <arm_group>
    <arm_group_label>Treatment Phase: Enantone</arm_group_label>
    <description>Participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Follow Up: Participants No longer Treated for CPP</arm_group_label>
    <description>Participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Follow Up: Treated with Non-Enantone GnRHa after Enantone</arm_group_label>
    <description>Participants who were continuing their CPP treatment with a non-Enantone gonadotropin releasing hormone agonist (GnRHa) after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enantone</intervention_name>
    <description>Enantone suspension for injection</description>
    <arm_group_label>Treatment Phase: Enantone</arm_group_label>
    <other_name>Leuprorelin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GnRH agonist</intervention_name>
    <description>A non-Enantone GnRH agonist</description>
    <arm_group_label>Follow Up: Treated with Non-Enantone GnRHa after Enantone</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Participants diagnosed with CPP will be observed.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Has diagnosis of idiopathic CPP.&#xD;
&#xD;
          2. Has been treated with leuprorelin acetate (Enantone) for at least 9 continuous months&#xD;
             of therapy with either a stable dose of high dose (greater than or equal to [&gt;=] 90&#xD;
             mcg/kg up to 180 mcg/kg) or low dose (&lt; 90 mcg/kg down to 30 mcg/kg).&#xD;
&#xD;
          3. Has initiated and completed treatment during the index period from September 1st 1998&#xD;
             to September 30th 2018.&#xD;
&#xD;
          4. Have the following information prior to initiation of enantone and at least one record&#xD;
             of each of the following parameters at the end of enantone treatment in the medical&#xD;
             records: Tanner staging, estradiol or testosterone level, and FSH and LH level. The&#xD;
             participant should have at least one record of bone age prior to the initiation&#xD;
             gonadotropin releasing hormone analogs (GnRHa) therapy with enantone to support the&#xD;
             diagnosis of CPP. In addition, should have at least one record of bone age during&#xD;
             treatment with enantone.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has been treated with leuprorelin acetate or any other GnRHa for conditions other than&#xD;
             CPP.&#xD;
&#xD;
          2. Has used any other GnRHa products for CPP treatment prior to initiation of enantone&#xD;
             therapy.&#xD;
&#xD;
          3. CPP participants with identified etiology, such as brain tumor or cranial irradiation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director Clinical Science</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Children's Hospital, Zhejiang University School of Medicine</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Childrens Hospital of Hunan province</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410007</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangsu Province Hosptial</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210036</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Jiangxi province</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <zip>330006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Shanghai</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital, Zhejiang University School of Medicine</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310053</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <results_first_submitted>September 30, 2019</results_first_submitted>
  <results_first_submitted_qc>September 30, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 24, 2019</results_first_posted>
  <last_update_submitted>March 7, 2022</last_update_submitted>
  <last_update_submitted_qc>March 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Puberty, Precocious</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leuprolide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/26/NCT02993926/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/26/NCT02993926/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 6 investigative sites in China from 24 Jun 2017 to 30 Sep 2018.</recruitment_details>
      <pre_assignment_details>Participants with a diagnosis of central precocious puberty (CPP) who previously received Enantone for at least 9 continuous months in clinical practice index period: 1 September 1998 to 30 September 2018 were enrolled in this study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment Phase: Enantone</title>
          <description>Participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
        </group>
        <group group_id="P2">
          <title>Follow Up: Participants No Longer Treated for CPP</title>
          <description>Participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
        </group>
        <group group_id="P3">
          <title>Follow Up: Treated With Non-Enantone GnRHa After Enantone</title>
          <description>Participants who were continuing their CPP treatment with a non-Enantone gonadotropin releasing hormone agonist (GnRHa) after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Enantone Treatment Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="76"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Changed CPP Therapy to Another GnRHa</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator Judgment</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Reason Not Specified</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Follow-Up Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="44"/>
                <participants group_id="P3" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="44"/>
                <participants group_id="P3" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set included all enrolled participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment Phase: Enantone</title>
          <description>Participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="108"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Age presented here is age at enantone treatment initiation (Years).</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.45" spread="1.124"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="104"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>China</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tanner Staging Evaluation</title>
          <description>Tanner Stage is used to define physical measurements of sexual development based on external primary and secondary sex characteristics. Female and male participants were evaluated for breast development and genital development respectively and both genders for pubic hair distribution based on a 5-stage scale ranging from Stage I (prepubertal/preadolescent characteristics) to Stage V (mature or adult characteristics). Participants classified as having progression if either breast/genitals or pubic hair were present. Otherwise participant is classified as regression or no progression.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Breast (Female) and Genitals (Male), Stage I</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Breast (Female) and Genitals (Male), Stage II</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Breast (Female) and Genitals (Male), Stage III</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Breast (Female) and Genitals (Male), Stage IV</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pubic Hair, Stage I</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pubic Hair, Stage II</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Peak Stimulated Luteinizing Hormone (LH)</title>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16.935" spread="10.7717"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Peak Stimulated Follicle Stimulating Hormone (FSH)</title>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14.407" spread="5.9366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Estradiol</title>
          <units>ng/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.3453" spread="18.1633"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Testosterone</title>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.4653" spread="127.7357"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Bone Age/Chronological Age Ratio</title>
          <description>Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.</description>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.22" spread="0.122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) During Enantone Treatment Phase</title>
        <description>A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.</description>
        <time_frame>During treatment with and up to 30 days post last dose of Enantone (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months)</time_frame>
        <population>Safety Analysis Set included all enrolled participants. Data in this outcome measure is reported separately for male and female participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Phase: Enantone (Male)</title>
            <description>Male participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
          <group group_id="O2">
            <title>Treatment Phase: Enantone (Female)</title>
            <description>Female participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) During Enantone Treatment Phase</title>
          <description>A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.</description>
          <population>Safety Analysis Set included all enrolled participants. Data in this outcome measure is reported separately for male and female participants.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With at Least One Treatment Emergent Adverse (TEAE) and Serious Adverse Event (SAE) During Follow-up Phase</title>
        <description>A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.</description>
        <time_frame>Mean duration of follow-up=8.75 months (range: 1.9-29.5 months) for No longer treated for CPP group; 10.80 months (range: 2.8-20.5 months) for Treated with Non-Enantone GnRHa group after treatment with Enantone (while on another GnRHa)</time_frame>
        <population>Safety Analysis Set included all enrolled participants. Data in this outcome measure is reported separately for male and female participants for follow-up period. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
        <group_list>
          <group group_id="O1">
            <title>Follow UP: Participants No Longer Treated for CPP (Male)</title>
            <description>Male participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O2">
            <title>Follow Up: Participants No Longer Treated for CPP (Female)</title>
            <description>Female participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O3">
            <title>FollowUp:Treated With Non-Enantone GnRHa After Enantone-Female</title>
            <description>Female participants who were continuing their CPP treatment with a non-Enantone GnRHa after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Treatment Emergent Adverse (TEAE) and Serious Adverse Event (SAE) During Follow-up Phase</title>
          <description>A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.</description>
          <population>Safety Analysis Set included all enrolled participants. Data in this outcome measure is reported separately for male and female participants for follow-up period. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="42"/>
                <count group_id="O3" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Enantone Treatment Phase</title>
        <description>Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.</description>
        <time_frame>The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months</time_frame>
        <population>Full Analysis Set (FAS) included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for the analysis of this outcome measure at the end of Treatment Phase.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Phase: Enantone (Male)</title>
            <description>Male participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
          <group group_id="O2">
            <title>Treatment Phase: Enantone (Female)</title>
            <description>Female participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Enantone Treatment Phase</title>
          <description>Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.</description>
          <population>Full Analysis Set (FAS) included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for the analysis of this outcome measure at the end of Treatment Phase.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="97.50"/>
                    <measurement group_id="O2" value="79.7" lower_limit="69.20" upper_limit="87.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Follow-Up Phase</title>
        <description>Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.</description>
        <time_frame>No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone</time_frame>
        <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Follow-up Phase. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
        <group_list>
          <group group_id="O1">
            <title>Follow UP: Participants No Longer Treated for CPP (Male)</title>
            <description>Male participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O2">
            <title>Follow Up: Participants No Longer Treated for CPP (Female)</title>
            <description>Female participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O3">
            <title>FollowUp:Treated With Non-Enantone GnRHa After Enantone-Female</title>
            <description>Female participants who were continuing their CPP treatment with a non-Enantone GnRHa after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Follow-Up Phase</title>
          <description>Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.</description>
          <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Follow-up Phase. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="0" lower_limit="0" upper_limit="97.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase</title>
        <description>The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.</description>
        <time_frame>The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months</time_frame>
        <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Treatment Phase.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Phase: Enantone (Male)</title>
            <description>Male participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
          <group group_id="O2">
            <title>Treatment Phase: Enantone (Female)</title>
            <description>Female participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase</title>
          <description>The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.</description>
          <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Treatment Phase.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>LH (U/L) Peak Value ≤ ULV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="2.50" upper_limit="100"/>
                    <measurement group_id="O2" value="98.1" lower_limit="89.74" upper_limit="99.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FSH (U/L) Peak Value ≤ ULV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="2.50" upper_limit="100"/>
                    <measurement group_id="O2" value="100" lower_limit="93.15" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase</title>
        <description>The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.</description>
        <time_frame>No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone</time_frame>
        <population>No data were available for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Follow UP: Participants No Longer Treated for CPP (Male)</title>
            <description>Male participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O2">
            <title>Follow Up: Participants No Longer Treated for CPP (Female)</title>
            <description>Female participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O3">
            <title>FollowUp:Treated With Non-Enantone GnRHa After Enantone-Female</title>
            <description>Female participants who were continuing their CPP treatment with a non-Enantone GnRHa after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase</title>
          <description>The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.</description>
          <population>No data were available for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>LH (U/L) Peak Value ≤ ULV</title>
            </class>
            <class>
              <title>FSH (U/L) Peak Value ≤ ULV</title>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase</title>
        <description>Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.</description>
        <time_frame>The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months</time_frame>
        <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Treatment Phase. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Phase: Enantone (Male)</title>
            <description>Male participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
          <group group_id="O2">
            <title>Treatment Phase: Enantone (Female)</title>
            <description>Female participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase</title>
          <description>Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.</description>
          <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Treatment Phase. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="103"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="39.76" upper_limit="100.00"/>
                    <measurement group_id="O2" value="74.8" lower_limit="65.24" upper_limit="82.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase</title>
        <description>Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.</description>
        <time_frame>No longer treated for CPP group-Month: 27 (766-855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group-Month 21 (586-675 days) post last dose of Enantone</time_frame>
        <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of analysis at the end of Follow-up Phase. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
        <group_list>
          <group group_id="O1">
            <title>Follow UP: Participants No Longer Treated for CPP (Male)</title>
            <description>Male participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O2">
            <title>Follow Up: Participants No Longer Treated for CPP (Female)</title>
            <description>Female participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O3">
            <title>FollowUp:Treated With Non-Enantone GnRHa After Enantone-Female</title>
            <description>Female participants who were continuing their CPP treatment with a non-Enantone GnRHa after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase</title>
          <description>Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.</description>
          <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of analysis at the end of Follow-up Phase. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="97.5"/>
                    <measurement group_id="O3" value="0" lower_limit="0" upper_limit="97.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Enantone Treatment Phase</title>
        <description>Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.</description>
        <time_frame>The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months</time_frame>
        <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Treatment Phase.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Phase: Enantone (Male)</title>
            <description>Male participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
          <group group_id="O2">
            <title>Treatment Phase: Enantone (Female)</title>
            <description>Female participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Enantone Treatment Phase</title>
          <description>Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.</description>
          <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Treatment Phase.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.0" lower_limit="19.41" upper_limit="99.37"/>
                    <measurement group_id="O2" value="90.2" lower_limit="82.24" upper_limit="95.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Follow-up Phase</title>
        <description>Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.</description>
        <time_frame>No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 18 (496-585 days) post last dose of Enantone</time_frame>
        <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Follow-up Phase. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
        <group_list>
          <group group_id="O1">
            <title>Follow UP: Participants No Longer Treated for CPP (Male)</title>
            <description>Male participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O2">
            <title>Follow Up: Participants No Longer Treated for CPP (Female)</title>
            <description>Female participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
          </group>
          <group group_id="O3">
            <title>FollowUp:Treated With Non-Enantone GnRHa After Enantone-Female</title>
            <description>Female participants who were continuing their CPP treatment with a non-Enantone GnRHa after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Follow-up Phase</title>
          <description>Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.</description>
          <population>FAS included all enrolled participants. Number of participants analyzed is the number of male or female participants with data available for analysis of this outcome measure at the end of Follow-up Phase. There were no observations available for male participants who continued therapy with a Non-Enantone GnRHa in the follow-up period.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="100" lower_limit="15.81" upper_limit="100"/>
                    <measurement group_id="O3" value="100" lower_limit="29.24" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment Phase - During treatment with Enantone and up to 30 days post last dose of Enantone (mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months); Follow-up Phase: No Longer Treated for CPP group - mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months; Treated with Non-Enantone GnRHa group - mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment Phase: Enantone</title>
          <description>Participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).</description>
        </group>
        <group group_id="E2">
          <title>Follow Up: Participants No Longer Treated for CPP</title>
          <description>Participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).</description>
        </group>
        <group group_id="E3">
          <title>Follow Up: Treated With Non-Enantone GnRHa After Enantone</title>
          <description>Participants who were continuing their CPP treatment with a non-Enantone gonadotropin releasing hormone agonist (GnRHa) after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Hair follicle tumour benign</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Keratosis follicular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Growth hormone deficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Refraction disorder</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Conjunctivitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Immunodeficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Herpes simplex</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Vulvitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Bone density decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Growth retardation</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Respiratory disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Dermatitis atopic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>All publications and presentations must be prepared in accordance with this section and the Clinical Study Site Agreement.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The enrollment of only 100 participants did not support the performance of subgroup analysis of outcomes by dose. Retrospective observational data is not controlled and therefore robust analysis could not be performed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Director</name_or_title>
      <organization>Takeda</organization>
      <phone>877-825-3327 ext +1</phone>
      <email>trialdisclosures@takeda.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/NCT02993926
org study id: Leuprorelin-5001
nct id: NCT02993926
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the long-term safety and efficacy of Enantone in the
      treatment of CPP in Chinese participants.
The drug being evaluated in this study is called Enantone (leuprorelin). Enantone is used to
      treat children who have CPP. This study will look at long term safety and efficacy of
      leuprorelin in the treatment of Chinese participants with CPP.

      The study will enroll approximately 300 participants.

      All participants who have received leuprorelin 30 mcg/kg to <90 mcg/kg or 90 mcg/kg to 180
      mcg/kg per body weight, injection, subcutaneously, every 4 weeks up to at least 9 continuous
      months during the index period from September 1st 1998 to September 30th 2018 will be
      observed.

      This multi-center trial will be conducted in China. Data will be collected over period of 20
      months.
observational model: Cohort
time perspective: Retrospective
measure: Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) During Enantone Treatment Phase
time frame: During treatment with and up to 30 days post last dose of Enantone (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months)
description: A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
measure: Number of Participants With at Least One Treatment Emergent Adverse (TEAE) and Serious Adverse Event (SAE) During Follow-up Phase
time frame: Mean duration of follow-up=8.75 months (range: 1.9-29.5 months) for No longer treated for CPP group; 10.80 months (range: 2.8-20.5 months) for Treated with Non-Enantone GnRHa group after treatment with Enantone (while on another GnRHa)
description: A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
measure: Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Enantone Treatment Phase
time frame: The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months
description: Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.
measure: Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Follow-Up Phase
time frame: No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone
description: Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.
measure: Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase
time frame: The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months
description: The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.
measure: Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase
time frame: No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone
description: The LH suppression is defined as peak LH ≤2 U/L for female and peak LH ≤2.7 U/L for male. The FSH suppression is defined as peak FSH ≤6.7 U/L for female and peak FSH ≤3.7 U/L for male. Post Stimulation Test, the peak values for LH and FSH suppression below Upper Limit Value (ULV) are reported.
measure: Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase
time frame: The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months
description: Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.
measure: Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase
time frame: No longer treated for CPP group-Month: 27 (766-855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group-Month 21 (586-675 days) post last dose of Enantone
description: Estradiol or Testosterone, suppressed below Upper Limit Value (ULV) were reported. The ULV for estradiol and testosterone were 20 pg/mL and 7.34 nmol/L, respectively.
measure: Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Enantone Treatment Phase
time frame: The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months
description: Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.
measure: Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Follow-up Phase
time frame: No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 18 (496-585 days) post last dose of Enantone
description: Bone age (BA) was estimated using an X-ray. Chronological age (CA) at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA was calculated.
arm group label: Treatment Phase: Enantone
description: Participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).
arm group label: Follow Up: Participants No longer Treated for CPP
description: Participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).
arm group label: Follow Up: Treated with Non-Enantone GnRHa after Enantone
description: Participants who were continuing their CPP treatment with a non-Enantone gonadotropin releasing hormone agonist (GnRHa) after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 [i.e. 1 day] to 12 months).
intervention type: Drug
intervention name: Enantone
description: Enantone suspension for injection
arm group label: Treatment Phase: Enantone
other name: Leuprorelin
intervention type: Drug
intervention name: GnRH agonist
description: A non-Enantone GnRH agonist
arm group label: Follow Up: Treated with Non-Enantone GnRHa after Enantone
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Medical Director Clinical Science
role: Study Director
affiliation: Takeda
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Puberty, Precocious
mesh term: Leuprolide
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The enrollment of only 100 participants did not support the performance of subgroup analysis of outcomes by dose. Retrospective observational data is not controlled and therefore robust analysis could not be performed.
point of contact: 