<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/NCT03274856</url>
  </required_header>
  <id_info>
    <org_study_id>GLWL-PWS</org_study_id>
    <nct_id>NCT03274856</nct_id>
  </id_info>
  <brief_title>A Study of GLWL-01 in Patients With Prader-Willi Syndrome</brief_title>
  <official_title>A Phase 2 Study to Evaluate Efficacy, Safety, and Pharmacokinetics of GLWL-01 in the Treatment of Patients With Prader-Willi Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GLWL Research Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GLWL Research Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to evaluate efficacy, safety, and pharmacokinetics of GLWL-01 in the&#xD;
      treatment of patients with Prader-Willi Syndrome (PWS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants will be assigned to one of two treatment sequences (GLWL-01/Placebo or&#xD;
      Placebo/GLWL-01), with each sequence consisting of two treatment periods separated by a&#xD;
      washout period&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 20, 2018</start_date>
  <completion_date type="Actual">June 12, 2019</completion_date>
  <primary_completion_date type="Actual">June 12, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)</measure>
    <time_frame>Up to approximately 4 weeks of double-blind treatment</time_frame>
    <description>GLWL-01 compared with placebo on the post-treatment HQ-CT score. Total range of score of zero to 36, with higher score indicating a worse outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs</measure>
    <time_frame>Baseline up to approximately 18 weeks</time_frame>
    <description>Evaluate the safety and tolerability of GLWL-01</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver Global Impression of Change (CGIC)</measure>
    <time_frame>Up to approximately 4 weeks of double-blind treatment</time_frame>
    <description>GLWL-01 compared with placebo in the CGIC. Score ranges from 1 to 7, with larger number indicating a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12)</measure>
    <time_frame>Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose</time_frame>
    <description>Pharmacokinetics (PK) after single and multiple oral dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Drug Concentration (Cmax)</measure>
    <time_frame>Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose</time_frame>
    <description>Pharmacokinetics after single and multiple oral dosing</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Prader-Willi Syndrome</condition>
  <arm_group>
    <arm_group_label>Treatment Sequence 1</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>GLWL-01 (450mg) twice a day/ Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Sequence 2</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Placebo / GLWL-01 (450mg), twice a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GLWL-01</intervention_name>
    <description>Oral administration of 3 capsules, twice a day</description>
    <arm_group_label>Treatment Sequence 1</arm_group_label>
    <arm_group_label>Treatment Sequence 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral administration of 3 capsules, twice a day</description>
    <arm_group_label>Treatment Sequence 1</arm_group_label>
    <arm_group_label>Treatment Sequence 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of PWS based on genetic confirmation using DNA method&#xD;
&#xD;
          -  Body mass index (BMI) of 27 to 60 kg/m2&#xD;
&#xD;
          -  No evidence of weight excursion beyond 10% of baseline weight&#xD;
&#xD;
          -  Patients must provide assent and have a reliable caregiver (must have been caring for&#xD;
             the patient for at least 6 months) who provides a separate written informed consent to&#xD;
             participate. The caregiver is expected to be the primary caregiver throughout the&#xD;
             study and must be in frequent contact with the patient (defined as at least 4 awake&#xD;
             hours per day). The caregiver must be able to communicate with site personnel and in&#xD;
             the investigator's opinion must have adequate literacy to complete questionnaires. If&#xD;
             a caregiver cannot continue, 1 caregiver replacement is allowed&#xD;
&#xD;
          -  Are on a stable diet and exercise regimen for &gt;2 months prior&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current enrollment in or discontinuation within the last 30 days from a clinical trial&#xD;
             involving any investigational drug or device&#xD;
&#xD;
          -  Are currently living in a group home for more than 50% of the time&#xD;
&#xD;
          -  A history or presence of other medical illness that indicates a medical problem that&#xD;
             would preclude study participation&#xD;
&#xD;
          -  Have an estimated glomerular filtration rate &lt;60 mL/minute/1.73 m2. Have&#xD;
             macroalbuminuria (defined as spot urine albumin to creatinine ratio of &gt;300 μg/mg) or&#xD;
             hematuria&#xD;
&#xD;
          -  Are hypertensive (defined as sitting systolic blood pressure (BP) greater than or&#xD;
             equal to (≥)140 millimeters of mercury (mmHg) and diastolic BP ≥90 mmHg)&#xD;
&#xD;
          -  Patients on weight loss medications within 30 days of dosing, or with a history of&#xD;
             bariatric surgery&#xD;
&#xD;
          -  Unable to refrain from or anticipates the use of:&#xD;
&#xD;
               1. Any drugs known to be significant inhibitors of Cytochrome P450, family 3,&#xD;
                  subfamily A (CYP)3A enzymes and/or P-glycoprotein (P-gp) including regular&#xD;
                  consumption of grapefruit or grapefruit juice for 14 days prior to the first&#xD;
                  dose. Acetaminophen (up to 2 grams per 24-hour period) may be permitted&#xD;
&#xD;
               2. Any drugs known to be significant inducers of Cytochrome P450, family 3,&#xD;
                  subfamily A (CYP3A) enzymes and/or P-gp, including St. John's Wort&#xD;
&#xD;
               3. Any medications that prolong the QT/QTc interval, unless the participant has been&#xD;
                  stable on the medication for at least 3 months and has a corrected QT interval&#xD;
                  (QTc) &lt;450 msec&#xD;
&#xD;
          -  Currently taking simvastatin &gt;10 mg per day, atorvastatin &gt;20 mg per day, or&#xD;
             lovastatin &gt;20 mg per day, or have a history of statin-induced myopathy/rhabdomyolysis&#xD;
&#xD;
          -  Unsuitable for inclusion in the study in the opinion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>GLWL Research Inc.</affiliation>
  </overall_official>
  <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>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals, Cleveland Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alberta Diabetes Institute, University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRCHUM</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2W 1T8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Ste-Justine</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <results_first_submitted>March 9, 2020</results_first_submitted>
  <results_first_submitted_qc>March 9, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 27, 2020</results_first_posted>
  <last_update_submitted>March 9, 2020</last_update_submitted>
  <last_update_submitted_qc>March 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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>June 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/56/NCT03274856/Prot_000.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>March 19, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/56/NCT03274856/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Five additional participants screened but not randomized</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment Sequence 1</title>
          <description>GLWL-01 (450mg) twice a day/ Placebo. Participants randomized to 1 of 2 treatment sequences; GLWL-01/placebo or placebo/GLWL-01 (Treatment Period 1 double-blind treatment phase/Treatment Period 2 double-blind treatment phase). During single-blind placebo lead-in phases, participants receive 3 capsules of 150-mg placebo twice daily (BID) for 14 days. During double-blind treatment phases, participants receive 3 capsules of 150-mg GLWL-01 (450 mg total dose) BID or identical placebo BID for 28 days</description>
        </group>
        <group group_id="P2">
          <title>Treatment Sequence 2</title>
          <description>Placebo / GLWL-01 (450mg), twice a day. Participants randomized to 1 of 2 treatment sequences; GLWL-01/placebo or placebo/GLWL-01 (Treatment Period 1 double-blind treatment phase/Treatment Period 2 double-blind treatment phase). During single-blind placebo lead-in phases, participants receive 3 capsules of 150-mg placebo twice daily (BID) for 14 days. During double-blind treatment phases, participants receive 3 capsules of 150-mg GLWL-01 (450 mg total dose) BID or identical placebo BID for 28 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment Sequence 1</title>
          <description>GLWL-01 (450mg) twice a day/ Placebo. Participants randomized to 1 of 2 treatment sequences; GLWL-01/placebo or placebo/GLWL-01 (Treatment Period 1 double-blind treatment phase/Treatment Period 2 double-blind treatment phase). During single-blind placebo lead-in phases, participants receive 3 capsules of 150-mg placebo twice daily (BID) for 14 days. During double-blind treatment phases, participants receive 3 capsules of 150-mg GLWL-01 (450 mg total dose) BID or identical placebo BID for 28 days</description>
        </group>
        <group group_id="B2">
          <title>Treatment Sequence 2</title>
          <description>Placebo / GLWL-01 (450mg), twice a day. Participants randomized to 1 of 2 treatment sequences; GLWL-01/placebo or placebo/GLWL-01 (Treatment Period 1 double-blind treatment phase/Treatment Period 2 double-blind treatment phase). During single-blind placebo lead-in phases, participants receive 3 capsules of 150-mg placebo twice daily (BID) for 14 days. During double-blind treatment phases, participants receive 3 capsules of 150-mg GLWL-01 (450 mg total dose) BID or identical placebo BID for 28 days</description>
        </group>
        <group group_id="B3">
          <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="10"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="19"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="22.0" spread="5.54"/>
                    <measurement group_id="B2" value="22.1" spread="4.83"/>
                    <measurement group_id="B3" value="22.1" spread="5.07"/>
                  </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="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)</title>
        <description>GLWL-01 compared with placebo on the post-treatment HQ-CT score. Total range of score of zero to 36, with higher score indicating a worse outcome.</description>
        <time_frame>Up to approximately 4 weeks of double-blind treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>GLWL-01</title>
            <description>Participants who received GLWL in either double blind treatment phase</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo in either double blind treatment phase</description>
          </group>
        </group_list>
        <measure>
          <title>Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)</title>
          <description>GLWL-01 compared with placebo on the post-treatment HQ-CT score. Total range of score of zero to 36, with higher score indicating a worse outcome.</description>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.9" spread="1.21"/>
                    <measurement group_id="O2" value="14.7" spread="1.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs</title>
        <description>Evaluate the safety and tolerability of GLWL-01</description>
        <time_frame>Baseline up to approximately 18 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>GLWL-01</title>
            <description>Participants who received GLWL in either double blind treatment phase</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo in either double blind treatment phase</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs</title>
          <description>Evaluate the safety and tolerability of GLWL-01</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Caregiver Global Impression of Change (CGIC)</title>
        <description>GLWL-01 compared with placebo in the CGIC. Score ranges from 1 to 7, with larger number indicating a worse outcome.</description>
        <time_frame>Up to approximately 4 weeks of double-blind treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>GLWL-01</title>
            <description>Participants who received GLWL in either double blind treatment phase</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants who received placebo in either double blind treatment phase</description>
          </group>
        </group_list>
        <measure>
          <title>Caregiver Global Impression of Change (CGIC)</title>
          <description>GLWL-01 compared with placebo in the CGIC. Score ranges from 1 to 7, with larger number indicating a worse outcome.</description>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="0.18"/>
                    <measurement group_id="O2" value="3.8" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12)</title>
        <description>Pharmacokinetics (PK) after single and multiple oral dosing</description>
        <time_frame>Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose</time_frame>
        <population>Because PK data were collected only during Treatment 1, and the patients were randomized 1:1 to GLWL-01 or placebo, PK data were available from 9 patients. Evaluable data only available to compute AUC for some participants</population>
        <group_list>
          <group group_id="O1">
            <title>GLWL-01 Single Dose</title>
            <description>Day 14 observation</description>
          </group>
          <group group_id="O2">
            <title>GLWL-01 Multiple Dose</title>
            <description>Day 42 observation</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12)</title>
          <description>Pharmacokinetics (PK) after single and multiple oral dosing</description>
          <population>Because PK data were collected only during Treatment 1, and the patients were randomized 1:1 to GLWL-01 or placebo, PK data were available from 9 patients. Evaluable data only available to compute AUC for some participants</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55608" spread="23.6"/>
                    <measurement group_id="O2" value="121620" spread="23.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Drug Concentration (Cmax)</title>
        <description>Pharmacokinetics after single and multiple oral dosing</description>
        <time_frame>Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>GLWL-01 Single Dose</title>
            <description>Day 14 observation</description>
          </group>
          <group group_id="O2">
            <title>GLWL-01 Multiple Dose</title>
            <description>Day 42 observation</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Drug Concentration (Cmax)</title>
          <description>Pharmacokinetics after single and multiple oral dosing</description>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7885" spread="34.4"/>
                    <measurement group_id="O2" value="13695" spread="29.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 18 weeks</time_frame>
      <desc>Treatment-emergent adverse event: An untoward medical occurrence that emerges during a defined treatment period, having been absent pretreatment, or worsens relative to the pretreatment state, and does not necessarily have to have a causal relationship with this treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>GLWL</title>
          <description>Participants who received GLWL in either double blind treatment phase</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants who received placebo in either double blind treatment phase</description>
        </group>
      </group_list>
      <serious_events>
        <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="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 20.0</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="8" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Faeces discoloured</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Faeces soft</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Nail infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Amenorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Menstruation delayed</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Menstruation irregular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Skin fissures</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Caroline Fortier</name_or_title>
      <organization>GLWL Research Inc</organization>
      <phone>1.514.708.4417</phone>
      <email>caroline.fortier@glwlresearch.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/NCT03274856
org study id: GLWL-PWS
nct id: NCT03274856
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The aim of this study is to evaluate efficacy, safety, and pharmacokinetics of GLWL-01 in the
      treatment of patients with Prader-Willi Syndrome (PWS).
Participants will be assigned to one of two treatment sequences (GLWL-01/Placebo or
      Placebo/GLWL-01), with each sequence consisting of two treatment periods separated by a
      washout period
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Post-treatment Total Score on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)
time frame: Up to approximately 4 weeks of double-blind treatment
description: GLWL-01 compared with placebo on the post-treatment HQ-CT score. Total range of score of zero to 36, with higher score indicating a worse outcome.
measure: Number of Participants With One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs
time frame: Baseline up to approximately 18 weeks
description: Evaluate the safety and tolerability of GLWL-01
measure: Caregiver Global Impression of Change (CGIC)
time frame: Up to approximately 4 weeks of double-blind treatment
description: GLWL-01 compared with placebo in the CGIC. Score ranges from 1 to 7, with larger number indicating a worse outcome.
measure: Area Under the Concentration Versus Time Curve From Time Zero to 12 Hours (AUC0-12)
time frame: Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose
description: Pharmacokinetics (PK) after single and multiple oral dosing
measure: Maximum Observed Drug Concentration (Cmax)
time frame: Day 14 and Day 42, pre-dose, and 0.5, 1, 2, 4, 6, and between 8 and 12 hours postdose
description: Pharmacokinetics after single and multiple oral dosing
arm group label: Treatment Sequence 1
arm group type: Other
description: GLWL-01 (450mg) twice a day/ Placebo
arm group label: Treatment Sequence 2
arm group type: Other
description: Placebo / GLWL-01 (450mg), twice a day
intervention type: Drug
intervention name: GLWL-01
description: Oral administration of 3 capsules, twice a day
arm group label: Treatment Sequence 1
arm group label: Treatment Sequence 2
intervention type: Drug
intervention name: Placebo
description: Oral administration of 3 capsules, twice a day
arm group label: Treatment Sequence 1
arm group label: Treatment Sequence 2
criteria: 
gender: All
minimum age: 16 Years
maximum age: 65 Years
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: GLWL Research Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Prader-Willi Syndrome
mesh term: Syndrome
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 