<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/NCT03770637</url>
  </required_header>
  <id_info>
    <org_study_id>XSGR-PBH-201</org_study_id>
    <nct_id>NCT03770637</nct_id>
  </id_info>
  <brief_title>Glucagon Ready to Use (RTU) in Subjects With Hyperinsulinemic Hypoglycemia After Bariatric Surgery</brief_title>
  <official_title>A Phase 2, Interventional, Randomized, Double-Blind, Placebo-Controlled Pilot Study of Glucagon RTU in Subjects Who Experience Hyperinsulinemic Hypoglycemia After Bariatric Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xeris Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xeris Pharmaceuticals</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a double-blind, placebo-controlled Phase 2 study to assess the efficacy, safety and&#xD;
      tolerability of Glucagon RTU when administered to subjects with a history of bariatric&#xD;
      surgery during episodes of post-postprandial hypoglycemia. Twelve eligible subjects will be&#xD;
      randomly assigned to receive Glucagon RTU or placebo at the first of two clinical research&#xD;
      center (CRC) visits, followed by the other treatment at the second CRC visit. Subjects will&#xD;
      be randomly assigned to either Glucagon RTU or Placebo for the duration of a 12-week&#xD;
      Outpatient Stage. A follow-up safety assessment visit will occur 14 to 28 days after a&#xD;
      subject's last dose of study drug.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 10, 2019</start_date>
  <completion_date type="Actual">February 26, 2020</completion_date>
  <primary_completion_date type="Actual">February 26, 2020</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>
    <intervention_model_description>A randomized, placebo-controlled, double-blind, two-treatment, 2-period, crossover in-patient phase followed by a placebo-controlled, double-blind, parallel two-treatment outpatient stage..</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>The sponsor, investigators/staff and subjects will be blinded to treatment assignment. Active study drug and placebo have the identical appearance (i.e., clear, colorless liquid), and both will be provided in identical vials with blinded labeling that does not reveal the contents of the vial.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Blood glucose recovery: CRC</measure>
    <time_frame>At 15 minutes following administration of study drug</time_frame>
    <description>Number of subjects with blood glucose &gt; 70 mg/dL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood glucose recovery: Out-patient</measure>
    <time_frame>At 15 minutes following administration of study drug</time_frame>
    <description>Frequency of blood glucose &gt; 70 mg/dL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Symptomatic Recovery: CRC</measure>
    <time_frame>At 15, 30, and 60 minutes following administration of study drug</time_frame>
    <description>Change from Baseline in Hypoglycemia Symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of severe hypoglycemia: CRC</measure>
    <time_frame>At 0-240 minutes following administration of study drug</time_frame>
    <description>Number of subjects requiring external assistance to treat hypoglycemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of severe hypoglycemia: Out-patient</measure>
    <time_frame>During 12 weeks of out-patient treatment</time_frame>
    <description>Frequency of external assistance to treat postprandial hypoglycemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of serious hypoglycemia: CRC</measure>
    <time_frame>At 0-240 minutes following administration of study drug</time_frame>
    <description>Number of subjects with blood glucose &lt; 54 mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of serious hypoglycemia: Out-patient</measure>
    <time_frame>During 12 weeks of out-patient treatment</time_frame>
    <description>Frequency of postprandial blood glucose &lt; 54 mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypoglycemia Fear Scale</measure>
    <time_frame>During 12 weeks of out-patient treatment</time_frame>
    <description>Change from Baseline in Hypoglycemia Fear Scale (HFS-2) Scores. The HFS-2 consists of two domains, Behavior, which has 15 questions, and Worry, which has 18 questions. Each question is assessed on a 5-point scale from 0=Never to 4=Almost Always. Lower scores indicate less fear of hypoglycemia, while higher scores indicate a greater level of fear.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EuroQol Health Questionnaire (EQ-5D)</measure>
    <time_frame>During 12 weeks of out-patient treatment</time_frame>
    <description>Change from Baseline in EQ-5D Score. This is a health assessment questionnaire with three domains. The first two domains of pain/discomfort and anxiety/depression are scored on a 5-point scale from 1=no pain/discomfort; not anxious or depressed to 5=extreme pain or discomfort; extremely anxious or depressed. For these two domains, lower scores indicate less pain/discomfort or anxiety/depression, while higher scores indicate increasing levels of pain/discomfort or anxiety/depression. The third domain of Health is assessed with a series of 5 visual analog scales, each scored from 0-100. On these VAS scales, high scores indicate better health, while low scores indicate worse health.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Hyperinsulinemic Hypoglycemia</condition>
  <arm_group>
    <arm_group_label>Glucagon RTU (glucagon injection)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Non-active vehicle for Glucagon RTU; 60 μL injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glucagon RTU</intervention_name>
    <description>Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe.</description>
    <arm_group_label>Glucagon RTU (glucagon injection)</arm_group_label>
    <other_name>glucagon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female&#xD;
&#xD;
          2. Aged 18 to 75 years of age, inclusive&#xD;
&#xD;
          3. Symptoms of hypoglycemia that developed after bariatric surgery (Roux-en-Y gastric&#xD;
             bypass [RYGB] only) in the absence of antidiabetic medications&#xD;
&#xD;
          4. History of bariatric surgery (RYGB only), at least 6 months prior to screening&#xD;
&#xD;
          5. Whipple's triad&#xD;
&#xD;
               1. Ability to both experience and recognize hypoglycemic awareness.&#xD;
&#xD;
               2. Documented glucose levels &lt; 54 mg/dL when experiencing symptoms suggestive of&#xD;
                  hypoglycemia&#xD;
&#xD;
               3. Relief of hypoglycemia symptoms when the glucose is raised to normal&#xD;
&#xD;
          6. Diagnosis of post-bariatric hypoglycemia (PBH) by a physician, requiring intervention&#xD;
             such as intake of oral carbohydrates. This diagnosis includes documentation of&#xD;
             endogenous hyperinsulinism in the presence of low plasma glucose.&#xD;
&#xD;
          7. In subjects with medical history of diabetes, medical documentation of postoperative&#xD;
             remission of diabetes mellitus (fasting glucose &lt; 110 mg/dL), and HbA1c &lt; 6% (or 42&#xD;
             mmol/mL) with all previous antidiabetic medication discontinued for at least 6 months&#xD;
             before screening.&#xD;
&#xD;
          8. Body mass index (BMI) ≤ 40 kg/m2&#xD;
&#xD;
          9. Willingness to follow all study procedures, including attending all clinic visits and&#xD;
             self-administering blinded study drug at home for 12 weeks&#xD;
&#xD;
         10. Understands the study procedures, alternative treatment available, and risks involved&#xD;
             with the study, and he/she voluntarily agrees to participate by giving written&#xD;
             informed consent&#xD;
&#xD;
         11. Women of childbearing potential must have a negative urine pregnancy test and agree to&#xD;
             use contraception and refrain from breast-feeding during the study and for at least 15&#xD;
             days after participating in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Documented hypoglycemia occurring in the fasting state (&gt; 12 hours fast) within 12&#xD;
             months of study entry&#xD;
&#xD;
          2. Hypoglycemic unawareness as evidenced by a Gold Scale score &gt; 4 at screening&#xD;
&#xD;
          3. Early Dumping Syndrome&#xD;
&#xD;
          4. Known insulinoma or adrenal insufficiency&#xD;
&#xD;
          5. Active treatment with any insulin/insulin secretagogues, or other diabetes medications&#xD;
             except for acarbose and glucagon-like peptide 1 (GLP-1) analogues&#xD;
&#xD;
          6. Chronic kidney disease Stage 4 or 5 or an estimated Glomerular Filtration Rate (eGFR)&#xD;
             &lt; 30 mL/min/1.73 m2 at screening&#xD;
&#xD;
          7. Hepatic disease, including serum alanine aminotransferase or aspartate&#xD;
             aminotransferase ≥ 3 times the upper limit of normal (ULN); hepatic synthetic&#xD;
             insufficiency as defined as serum albumin &lt; 3.0 g/dL&#xD;
&#xD;
          8. Congestive heart failure, New York Heart Association Class III or IV&#xD;
&#xD;
          9. History of myocardial infarction, unstable angina, or revascularization within 6&#xD;
             months prior to screening.&#xD;
&#xD;
         10. History of a cerebrovascular accident within 6 months prior to screening or with major&#xD;
             neurological deficits&#xD;
&#xD;
         11. Seizure disorder (other than with suspected or documented hypoglycemia).&#xD;
&#xD;
         12. Active malignancy, except for basal or squamous cell skin cancers&#xD;
&#xD;
         13. Personal or family history of pheochromocytoma or disorder with increased risk of&#xD;
             pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease)&#xD;
&#xD;
         14. Major surgical operation within 30 days prior to screening&#xD;
&#xD;
         15. Hematocrit ≤ 30%&#xD;
&#xD;
         16. Bleeding disorder, treatment with warfarin, or platelet count &lt; 50,000 /mm3&#xD;
&#xD;
         17. Active alcohol abuse or substance abuse (per investigator assessment)&#xD;
&#xD;
         18. Current chronic administration of oral or parenteral corticosteroids, however topical,&#xD;
             intraarticular, and inhaled corticosteroids are allowed&#xD;
&#xD;
         19. Use of an investigational drug within 15 days or 5 half-lives, whichever is longer,&#xD;
             prior to screening&#xD;
&#xD;
         20. Member of a special vulnerable populations such as pregnant women, prisoners,&#xD;
             institutionalized or incarcerated individuals, or others who may be considered&#xD;
             vulnerable&#xD;
&#xD;
         21. Any other medical condition or finding that in the opinion of the investigator or&#xD;
             sponsor, would compromise the safety of the subject or compromise the integrity of the&#xD;
             study data&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Colorado-Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Joslin Diabetes Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic- Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Early Phase Clinical Research</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>May 20, 2020</last_update_submitted>
  <last_update_submitted_qc>May 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>glucagon</keyword>
  <keyword>post-bariatric hypoglycemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Congenital Hyperinsulinism</mesh_term>
    <mesh_term>Nesidioblastosis</mesh_term>
    <mesh_term>Hypoglycemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glucagon</mesh_term>
    <mesh_term>Glucagon-Like Peptide 1</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>December 7, 2021</submitted>
    <returned>January 5, 2022</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03770637
org study id: XSGR-PBH-201
nct id: NCT03770637
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a double-blind, placebo-controlled Phase 2 study to assess the efficacy, safety and
      tolerability of Glucagon RTU when administered to subjects with a history of bariatric
      surgery during episodes of post-postprandial hypoglycemia. Twelve eligible subjects will be
      randomly assigned to receive Glucagon RTU or placebo at the first of two clinical research
      center (CRC) visits, followed by the other treatment at the second CRC visit. Subjects will
      be randomly assigned to either Glucagon RTU or Placebo for the duration of a 12-week
      Outpatient Stage. A follow-up safety assessment visit will occur 14 to 28 days after a
      subject's last dose of study drug.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: A randomized, placebo-controlled, double-blind, two-treatment, 2-period, crossover in-patient phase followed by a placebo-controlled, double-blind, parallel two-treatment outpatient stage..
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: The sponsor, investigators/staff and subjects will be blinded to treatment assignment. Active study drug and placebo have the identical appearance (i.e., clear, colorless liquid), and both will be provided in identical vials with blinded labeling that does not reveal the contents of the vial.
measure: Blood glucose recovery: CRC
time frame: At 15 minutes following administration of study drug
description: Number of subjects with blood glucose > 70 mg/dL
measure: Blood glucose recovery: Out-patient
time frame: At 15 minutes following administration of study drug
description: Frequency of blood glucose > 70 mg/dL
measure: Symptomatic Recovery: CRC
time frame: At 15, 30, and 60 minutes following administration of study drug
description: Change from Baseline in Hypoglycemia Symptoms
measure: Incidence of severe hypoglycemia: CRC
time frame: At 0-240 minutes following administration of study drug
description: Number of subjects requiring external assistance to treat hypoglycemia
measure: Incidence of severe hypoglycemia: Out-patient
time frame: During 12 weeks of out-patient treatment
description: Frequency of external assistance to treat postprandial hypoglycemia
measure: Incidence of serious hypoglycemia: CRC
time frame: At 0-240 minutes following administration of study drug
description: Number of subjects with blood glucose < 54 mg/dL
measure: Incidence of serious hypoglycemia: Out-patient
time frame: During 12 weeks of out-patient treatment
description: Frequency of postprandial blood glucose < 54 mg/dL
measure: Hypoglycemia Fear Scale
time frame: During 12 weeks of out-patient treatment
description: Change from Baseline in Hypoglycemia Fear Scale (HFS-2) Scores. The HFS-2 consists of two domains, Behavior, which has 15 questions, and Worry, which has 18 questions. Each question is assessed on a 5-point scale from 0=Never to 4=Almost Always. Lower scores indicate less fear of hypoglycemia, while higher scores indicate a greater level of fear.
measure: EuroQol Health Questionnaire (EQ-5D)
time frame: During 12 weeks of out-patient treatment
description: Change from Baseline in EQ-5D Score. This is a health assessment questionnaire with three domains. The first two domains of pain/discomfort and anxiety/depression are scored on a 5-point scale from 1=no pain/discomfort; not anxious or depressed to 5=extreme pain or discomfort; extremely anxious or depressed. For these two domains, lower scores indicate less pain/discomfort or anxiety/depression, while higher scores indicate increasing levels of pain/discomfort or anxiety/depression. The third domain of Health is assessed with a series of 5 visual analog scales, each scored from 0-100. On these VAS scales, high scores indicate better health, while low scores indicate worse health.
arm group label: Glucagon RTU (glucagon injection)
arm group type: Experimental
description: Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon)
arm group label: Placebo
arm group type: Placebo Comparator
description: Non-active vehicle for Glucagon RTU; 60 μL injection
intervention type: Drug
intervention name: Glucagon RTU
description: Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe.
arm group label: Glucagon RTU (glucagon injection)
other name: glucagon
intervention type: Other
intervention name: Placebo
description: The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle).
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Congenital Hyperinsulinism
mesh term: Nesidioblastosis
mesh term: Hypoglycemia
mesh term: Glucagon
mesh term: Glucagon-Like Peptide 1
sharing ipd: No
submitted: December 7, 2021
returned: January 5, 2022