<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/NCT03790865</url>
  </required_header>
  <id_info>
    <org_study_id>AZP01-CLI-003</org_study_id>
    <nct_id>NCT03790865</nct_id>
  </id_info>
  <brief_title>Effects of Livoletide (AZP-531) on Food-related Behaviors in Patients With Prader-Willi Syndrome</brief_title>
  <acronym>ZEPHYR</acronym>
  <official_title>A Phase 2b/3 Study to Evaluate the Safety, Tolerability, and Effects of Livoletide (AZP-531), an Unacylated Ghrelin Analogue, on Food-related Behaviors in Patients With Prader-Willi Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Millendo Therapeutics SAS</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Millendo Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 2b/3 double-blind, placebo-controlled study will evaluate the safety,&#xD;
      tolerability, and effects of livoletide on food-related behaviors in patients with&#xD;
      Prader-Willi Syndrome (PWS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The protocol includes 2 consecutive parts:&#xD;
&#xD;
        1. The first part is a Phase 2b dose-response study consisting of a 3-month double-blind,&#xD;
           placebo-controlled Core Period followed by a 9-month Extension Period.&#xD;
&#xD;
        2. The second part is a Phase 3 study consisting of a 6-month double-blind,&#xD;
           placebo-controlled Core Period followed by a 6-month Extension Period. Phase 3 may be&#xD;
           initiated following review of safety and efficacy results at the completion of the Phase&#xD;
           2b Core Period.&#xD;
&#xD;
      A total of approximately 50 patients per group (8 to 65 years of age) will be randomized&#xD;
      (approximately 150 patients in total). In addition to this cohort of 150 patients, a separate&#xD;
      cohort of patients 4 to 7 years of age will also be randomized.&#xD;
&#xD;
      Note: The 8-65 year old cohort has been fully enrolled. Enrollment into the 4-7 year age&#xD;
      cohort remains ongoing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Livoletide did not result in a statistically significant improvement in hyperphagia and&#xD;
    food-related behaviors&#xD;
  </why_stopped>
  <start_date type="Actual">March 25, 2019</start_date>
  <completion_date type="Actual">May 25, 2020</completion_date>
  <primary_completion_date type="Actual">February 26, 2020</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT)</measure>
    <time_frame>Baseline to month 3</time_frame>
    <description>Change from baseline to the end of the 3-month Core Period for HQ-CT total score. The HQ-CT score range is 0 to 36 where the higher score represents more severe abnormal food related behaviors.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese</measure>
    <time_frame>Baseline to month 3</time_frame>
    <description>Total body fat mass was assessed using dual energy X-ray absorptiometry (DXA) scan. DXAs were conducted at each local facility using standardized procedures and settings.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese</measure>
    <time_frame>Baseline to month 3</time_frame>
    <description>The waist circumference was measured in fasting condition at the superior border of iliac crest, according to recommendations from the Anthropometry Procedures Manual of the National Health and Nutrition Examination Survey, Revised 2007.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese</measure>
    <time_frame>Baseline to month 3</time_frame>
    <description>Patients were weighed in fasting condition, clothed (underwear, light gown or light clothing), without footwear or heavy jewelry, using a calibrated scale. The same scale should be used throughout the study if possible. The conditions under which patients are weighed should be kept consistent if possible.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">158</enrollment>
  <condition>Prader-Willi Syndrome</condition>
  <condition>Hyperphagia</condition>
  <arm_group>
    <arm_group_label>Low-Dose Livoletide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High-Dose Livoletide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Livoletide</intervention_name>
    <description>Daily subcutaneous injection</description>
    <arm_group_label>High-Dose Livoletide</arm_group_label>
    <arm_group_label>Low-Dose Livoletide</arm_group_label>
    <other_name>AZP-531</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Daily subcutaneous injection</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed genetic diagnosis of PWS&#xD;
&#xD;
          -  Evidence of increased appetite or hyperphagia&#xD;
&#xD;
          -  Patient must have a single primary caregiver who should be available for certain&#xD;
             durations of the study&#xD;
&#xD;
          -  BMI ≤ 65 kg/m2&#xD;
&#xD;
          -  Growth hormone treatment permitted if doses have been stable for at least 1 month&#xD;
             prior to screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of chronic liver disease&#xD;
&#xD;
          -  Type 1 diabetes mellitus&#xD;
&#xD;
          -  HbA1c &gt; 10%&#xD;
&#xD;
          -  Body weight &lt;20 kg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California - Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rady Children's Hospital - San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospitals and Clinics of Minnesota-Minneapolis</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winthrop University Hospital</name>
      <address>
        <city>Mineola</city>
        <state>New York</state>
        <zip>11501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Presbyterian Morgan Stanley Children's Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital</name>
      <address>
        <city>Camperdown</city>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Melbourne</city>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Perth Children's Hospital</name>
      <address>
        <city>Nedlands</city>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Childrens Hospital at Westmead</name>
      <address>
        <city>Westmead</city>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire d'Angers</name>
      <address>
        <city>Angers</city>
        <zip>49100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Lyon - Hopital Femmes Mere Enfant</name>
      <address>
        <city>Bron</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pitie Salpetriere</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Necker-Enfants Malades</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Toulouse - Hospital Rangueil</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Toulouse - Hopital des Enfants</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Federico II</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Pediatrico Bambino Gesù</name>
      <address>
        <city>Roma</city>
        <zip>00165</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus University Medical Center</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stichting Kind en Groei</name>
      <address>
        <city>Rotterdam</city>
        <zip>3016</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Alicante</name>
      <address>
        <city>Alicante</city>
        <zip>03010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Cruces</name>
      <address>
        <city>Barakaldo</city>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sant Joan de Deu</name>
      <address>
        <city>Barcelona</city>
        <zip>08950</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Corporacio Sanitaria Parc Tauli - Hospital de Sabadell</name>
      <address>
        <city>Sabadell</city>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Tayside</name>
      <address>
        <city>Dundee</city>
        <zip>DD1 9SY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chelsea and Westminster Hospital</name>
      <address>
        <city>London</city>
        <zip>SW109NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College London</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>France</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>December 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <results_first_submitted>January 21, 2021</results_first_submitted>
  <results_first_submitted_qc>February 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 17, 2021</results_first_posted>
  <last_update_submitted>February 8, 2021</last_update_submitted>
  <last_update_submitted_qc>February 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prader-Willi Syndrome</keyword>
  <keyword>PWS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prader-Willi Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Hyperphagia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <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>March 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03790865/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 31, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03790865/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Original protocol:&#xD;
for Phase 2b, a total of 50 patients per group will need to be randomized.&#xD;
Amendment v1.2:&#xD;
for Phase 2b, a total of approximately 50 patients per group (8 to 65 years of age) will need to be randomized. In addition to this cohort of 150 patients, a separate cohort of patients 4 to 7 years of age will also be randomized.</recruitment_details>
      <pre_assignment_details>Screening Period was up to 4 weeks. After signing informed consent, patients with Prader-Willi Syndrome entered the Screening Period to assess preliminary eligibility for the study based on the inclusion and exclusion criteria. In addition, pertinent information was collected such as past medical history, demographic data, and prior and current medications</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Low-Dose Livoletide</title>
          <description>Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
        </group>
        <group group_id="P2">
          <title>High-Dose Livoletide</title>
          <description>Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Daily subcutaneous injection of 0.9% sodium chloride for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.&#xD;
Placebo: Daily subcutaneous injection</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
                <participants group_id="P2" count="52"/>
                <participants group_id="P3" count="54"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
                <participants group_id="P2" count="50"/>
                <participants group_id="P3" count="54"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Low-Dose Livoletide</title>
          <description>Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
        </group>
        <group group_id="B2">
          <title>High-Dose Livoletide</title>
          <description>Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.&#xD;
Placebo: Daily subcutaneous injection</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="52"/>
            <count group_id="B2" value="52"/>
            <count group_id="B3" value="54"/>
            <count group_id="B4" value="158"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="74"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20.7" spread="9.20"/>
                    <measurement group_id="B2" value="19.7" spread="8.27"/>
                    <measurement group_id="B3" value="19.4" spread="8.03"/>
                    <measurement group_id="B4" value="19.9" spread="8.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="88"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="22"/>
                    <measurement group_id="B4" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="110"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="36"/>
                    <measurement group_id="B4" value="109"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Netherlands</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Belgium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline HQ-CT</title>
          <description>The hyperphagia questionnaire for clinical trials (HQ-CT) total score range is 0 to 36 where the higher score represents more severe abnormal food related behaviors.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20.4" spread="6.37"/>
                    <measurement group_id="B2" value="19.5" spread="6.34"/>
                    <measurement group_id="B3" value="20.5" spread="5.87"/>
                    <measurement group_id="B4" value="20.2" spread="6.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT)</title>
        <description>Change from baseline to the end of the 3-month Core Period for HQ-CT total score. The HQ-CT score range is 0 to 36 where the higher score represents more severe abnormal food related behaviors.</description>
        <time_frame>Baseline to month 3</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.</population>
        <group_list>
          <group group_id="O1">
            <title>Low-Dose Livoletide</title>
            <description>Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>High-Dose Livoletide</title>
            <description>Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.&#xD;
Placebo: Daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT)</title>
          <description>Change from baseline to the end of the 3-month Core Period for HQ-CT total score. The HQ-CT score range is 0 to 36 where the higher score represents more severe abnormal food related behaviors.</description>
          <population>The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="52"/>
                <count group_id="O3" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.1" spread="7.76"/>
                    <measurement group_id="O2" value="-3.6" spread="6.08"/>
                    <measurement group_id="O3" value="-3.3" spread="5.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.025</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>4</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese</title>
        <description>Total body fat mass was assessed using dual energy X-ray absorptiometry (DXA) scan. DXAs were conducted at each local facility using standardized procedures and settings.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
        <time_frame>Baseline to month 3</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.&#xD;
For this endpoint, only patients considered overweight/obese at baseline were included in the analysis.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</population>
        <group_list>
          <group group_id="O1">
            <title>Low-Dose Livoletide</title>
            <description>Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>High-Dose Livoletide</title>
            <description>Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.&#xD;
Placebo: Daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese</title>
          <description>Total body fat mass was assessed using dual energy X-ray absorptiometry (DXA) scan. DXAs were conducted at each local facility using standardized procedures and settings.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
          <population>The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.&#xD;
For this endpoint, only patients considered overweight/obese at baseline were included in the analysis.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.33" spread="3.806"/>
                    <measurement group_id="O2" value="3.48" spread="4.429"/>
                    <measurement group_id="O3" value="-0.36" spread="4.302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese</title>
        <description>The waist circumference was measured in fasting condition at the superior border of iliac crest, according to recommendations from the Anthropometry Procedures Manual of the National Health and Nutrition Examination Survey, Revised 2007.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
        <time_frame>Baseline to month 3</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.&#xD;
For this endpoint, only patients considered overweight/obese at baseline were included in the analysis.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</population>
        <group_list>
          <group group_id="O1">
            <title>Low-Dose Livoletide</title>
            <description>Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>High-Dose Livoletide</title>
            <description>Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.&#xD;
Placebo: Daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese</title>
          <description>The waist circumference was measured in fasting condition at the superior border of iliac crest, according to recommendations from the Anthropometry Procedures Manual of the National Health and Nutrition Examination Survey, Revised 2007.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
          <population>The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.&#xD;
For this endpoint, only patients considered overweight/obese at baseline were included in the analysis.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</population>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.92" spread="5.703"/>
                    <measurement group_id="O2" value="0.11" spread="4.969"/>
                    <measurement group_id="O3" value="-0.45" spread="3.674"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese</title>
        <description>Patients were weighed in fasting condition, clothed (underwear, light gown or light clothing), without footwear or heavy jewelry, using a calibrated scale. The same scale should be used throughout the study if possible. The conditions under which patients are weighed should be kept consistent if possible.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
        <time_frame>Baseline to month 3</time_frame>
        <population>The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.&#xD;
For this endpoint, only patients considered overweight/obese at baseline were included in the analysis.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</population>
        <group_list>
          <group group_id="O1">
            <title>Low-Dose Livoletide</title>
            <description>Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>High-Dose Livoletide</title>
            <description>Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.&#xD;
Placebo: Daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese</title>
          <description>Patients were weighed in fasting condition, clothed (underwear, light gown or light clothing), without footwear or heavy jewelry, using a calibrated scale. The same scale should be used throughout the study if possible. The conditions under which patients are weighed should be kept consistent if possible.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</description>
          <population>The Full Analysis Set (FAS) included all randomized patients. Efficacy analyses for the Phase 2b Core Period were performed on the FAS.&#xD;
For this endpoint, only patients considered overweight/obese at baseline were included in the analysis.&#xD;
Overweight/obese patients were defined as follows:&#xD;
patients ≥18 years of age: BMI ≥27 kg/m2&#xD;
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.39" spread="3.313"/>
                    <measurement group_id="O2" value="1.79" spread="2.079"/>
                    <measurement group_id="O3" value="1.06" spread="2.589"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The analysis of treatment-emergent adverse events (TEAEs) was done starting first dose of study drug and through 30 days after the end of the treatment period</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Low-Dose Livoletide</title>
          <description>Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
        </group>
        <group group_id="E2">
          <title>High-Dose Livoletide</title>
          <description>Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.&#xD;
Livoletide: Daily subcutaneous injection</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.&#xD;
Placebo: Daily subcutaneous injection</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 22.0</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="52"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Impulse control disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA version 22.0</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="34" subjects_at_risk="52"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="52"/>
                <counts group_id="E3" subjects_affected="34" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="10" subjects_affected="8" subjects_at_risk="52"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="11" subjects_affected="8" subjects_at_risk="52"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="52"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Injection site erythma</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Injection site hematoma</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Injection site mass</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Upper respiration infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood pressure systolic increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatillomania</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="52"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The double-blind, placebo-controlled phase 2b study did not meet the primary endpoint or any of the secondary endpoints. Therefore, the Sponsor has decided to discontinue further development of livoletide.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Clinical Trial Information</name_or_title>
      <organization>Millendo Therapeutics</organization>
      <phone>+1 734-845-9000</phone>
      <email>millendo@millendo.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/NCT03790865
org study id: AZP01-CLI-003
nct id: NCT03790865
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This Phase 2b/3 double-blind, placebo-controlled study will evaluate the safety,
      tolerability, and effects of livoletide on food-related behaviors in patients with
      Prader-Willi Syndrome (PWS).
The protocol includes 2 consecutive parts:

        1. The first part is a Phase 2b dose-response study consisting of a 3-month double-blind,
           placebo-controlled Core Period followed by a 9-month Extension Period.

        2. The second part is a Phase 3 study consisting of a 6-month double-blind,
           placebo-controlled Core Period followed by a 6-month Extension Period. Phase 3 may be
           initiated following review of safety and efficacy results at the completion of the Phase
           2b Core Period.

      A total of approximately 50 patients per group (8 to 65 years of age) will be randomized
      (approximately 150 patients in total). In addition to this cohort of 150 patients, a separate
      cohort of patients 4 to 7 years of age will also be randomized.

      Note: The 8-65 year old cohort has been fully enrolled. Enrollment into the 4-7 year age
      cohort remains ongoing.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT)
time frame: Baseline to month 3
description: Change from baseline to the end of the 3-month Core Period for HQ-CT total score. The HQ-CT score range is 0 to 36 where the higher score represents more severe abnormal food related behaviors.
measure: Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese
time frame: Baseline to month 3
description: Total body fat mass was assessed using dual energy X-ray absorptiometry (DXA) scan. DXAs were conducted at each local facility using standardized procedures and settings.
Overweight/obese patients were defined as follows:
patients ≥18 years of age: BMI ≥27 kg/m2
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex
measure: Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese
time frame: Baseline to month 3
description: The waist circumference was measured in fasting condition at the superior border of iliac crest, according to recommendations from the Anthropometry Procedures Manual of the National Health and Nutrition Examination Survey, Revised 2007.
Overweight/obese patients were defined as follows:
patients ≥18 years of age: BMI ≥27 kg/m2
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex
measure: Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese
time frame: Baseline to month 3
description: Patients were weighed in fasting condition, clothed (underwear, light gown or light clothing), without footwear or heavy jewelry, using a calibrated scale. The same scale should be used throughout the study if possible. The conditions under which patients are weighed should be kept consistent if possible.
Overweight/obese patients were defined as follows:
patients ≥18 years of age: BMI ≥27 kg/m2
patients 4-17 years of age: BMI ≥90th percentile for the same age and sex
arm group label: Low-Dose Livoletide
arm group type: Experimental
description: Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period.
arm group label: High-Dose Livoletide
arm group type: Experimental
description: Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period.
arm group label: Placebo
arm group type: Placebo Comparator
description: Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period.
intervention type: Drug
intervention name: Livoletide
description: Daily subcutaneous injection
arm group label: High-Dose Livoletide
arm group label: Low-Dose Livoletide
other name: AZP-531
intervention type: Drug
intervention name: Placebo
description: Daily subcutaneous injection
arm group label: Placebo
criteria: 
gender: All
minimum age: 4 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Belgium
country: France
country: Italy
country: Netherlands
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Prader-Willi Syndrome
mesh term: Syndrome
mesh term: Hyperphagia
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The double-blind, placebo-controlled phase 2b study did not meet the primary endpoint or any of the secondary endpoints. Therefore, the Sponsor has decided to discontinue further development of livoletide.
point of contact: 