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Glucagon Ready to Use (RTU) in Subjects With Hyperinsulinemic Hypoglycemia After Bariatric Surgery

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ClinicalTrials.gov Identifier: NCT03770637
Recruitment Status : Recruiting
First Posted : December 10, 2018
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Xeris Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE December 7, 2018
First Posted Date  ICMJE December 10, 2018
Last Update Posted Date June 6, 2019
Actual Study Start Date  ICMJE May 10, 2019
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2018)
  • Blood glucose recovery: CRC [ Time Frame: At 15 minutes following administration of study drug ]
    Number of subjects with blood glucose > 70 mg/dL
  • Blood glucose recovery: Out-patient [ Time Frame: At 15 minutes following administration of study drug ]
    Frequency of blood glucose > 70 mg/dL
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03770637 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2018)
  • Symptomatic Recovery: CRC [ Time Frame: At 15, 30, and 60 minutes following administration of study drug ]
    Change from Baseline in Hypoglycemia Symptoms
  • Incidence of severe hypoglycemia: CRC [ Time Frame: At 0-240 minutes following administration of study drug ]
    Number of subjects requiring external assistance to treat hypoglycemia
  • Incidence of severe hypoglycemia: Out-patient [ Time Frame: During 12 weeks of out-patient treatment ]
    Frequency of external assistance to treat postprandial hypoglycemia
  • Incidence of serious hypoglycemia: CRC [ Time Frame: At 0-240 minutes following administration of study drug ]
    Number of subjects with blood glucose < 54 mg/dL
  • Incidence of serious hypoglycemia: Out-patient [ Time Frame: During 12 weeks of out-patient treatment ]
    Frequency of postprandial blood glucose < 54 mg/dL
  • Hypoglycemia Fear Scale [ Time Frame: During 12 weeks of out-patient treatment ]
    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.
  • EuroQol Health Questionnaire (EQ-5D) [ Time Frame: During 12 weeks of out-patient treatment ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2018)
  • Symptomatic Recovery: CRC [ Time Frame: At 15, 30, and 60 minutes following administration of study drug ]
    Change from Baseline in Hypoglycemia Symptoms
  • Incidence of severe hypoglycemia: CRC [ Time Frame: At 0-240 minutes following administration of study drug ]
    Number of subjects requiring external assistance to treat hypoglycemia
  • Incidence of severe hypoglycemia: Out-patient [ Time Frame: During 12 weeks of out-patient treatment ]
    Frequency of external assistance to treat postprandial hypoglycemia
  • Incidence of serious hypoglycemia: CRC [ Time Frame: At 0-240 minutes following administration of study drug ]
    Number of subjects with blood glucose < 54 mg/dL
  • Incidence of serious hypoglycemia: Out-patient [ Time Frame: During 12 weeks of out-patient treatment ]
    Frequency of postprandial blood glucose < 54 mg/dL
  • Hypoglycemia Fear Scale [ Time Frame: During 12 weeks of out-patient treatment ]
    Change from Baseline in Hypoglycemia Fear Scale (HFS-2)
  • EuroQol Health Questionnaire (EQ-5D) [ Time Frame: During 12 weeks of out-patient treatment ]
    Change from Baseline in EQ-5D Score
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Glucagon Ready to Use (RTU) in Subjects With Hyperinsulinemic Hypoglycemia After Bariatric Surgery
Official Title  ICMJE A Phase 2, Interventional, Randomized, Double-Blind, Placebo-Controlled Pilot Study of Glucagon RTU in Subjects Who Experience Hyperinsulinemic Hypoglycemia After Bariatric Surgery
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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..
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.
Primary Purpose: Treatment
Condition  ICMJE Hyperinsulinemic Hypoglycemia
Intervention  ICMJE
  • Drug: Glucagon RTU
    Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe.
    Other Name: glucagon
  • Other: Placebo
    The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle).
Study Arms  ICMJE
  • Experimental: Glucagon RTU (glucagon injection)
    Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon)
    Intervention: Drug: Glucagon RTU
  • Placebo Comparator: Placebo
    Non-active vehicle for Glucagon RTU; 60 μL injection
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 7, 2018)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female
  2. Aged 18 to 75 years of age, inclusive
  3. Symptoms of hypoglycemia that developed after bariatric surgery (Roux-en-Y gastric bypass [RYGB] only) in the absence of antidiabetic medications
  4. History of bariatric surgery (RYGB only), at least 6 months prior to screening
  5. Whipple's triad

    1. Ability to both experience and recognize hypoglycemic awareness.
    2. Documented glucose levels < 54 mg/dL when experiencing symptoms suggestive of hypoglycemia
    3. Relief of hypoglycemia symptoms when the glucose is raised to normal
  6. Diagnosis of post-bariatric hypoglycemia (PBH) by a physician, requiring intervention such as intake of oral carbohydrates. This diagnosis includes documentation of endogenous hyperinsulinism in the presence of low plasma glucose.
  7. In subjects with medical history of diabetes, medical documentation of postoperative remission of diabetes mellitus (fasting glucose < 110 mg/dL), and HbA1c < 6% (or 42 mmol/mL) with all previous antidiabetic medication discontinued for at least 6 months before screening.
  8. Body mass index (BMI) ≤ 40 kg/m2
  9. Willingness to follow all study procedures, including attending all clinic visits and self-administering blinded study drug at home for 12 weeks
  10. Understands the study procedures, alternative treatment available, and risks involved with the study, and he/she voluntarily agrees to participate by giving written informed consent
  11. Women of childbearing potential must have a negative urine pregnancy test and agree to use contraception and refrain from breast-feeding during the study and for at least 15 days after participating in the study.

Exclusion Criteria:

  1. Documented hypoglycemia occurring in the fasting state (> 12 hours fast) within 12 months of study entry
  2. Hypoglycemic unawareness as evidenced by a Gold Scale score > 4 at screening
  3. Early Dumping Syndrome
  4. Known insulinoma or adrenal insufficiency
  5. Active treatment with any insulin/insulin secretagogues, or other diabetes medications except for acarbose and glucagon-like peptide 1 (GLP-1) analogues
  6. Chronic kidney disease Stage 4 or 5 or an estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m2 at screening
  7. Hepatic disease, including serum alanine aminotransferase or aspartate aminotransferase ≥ 3 times the upper limit of normal (ULN); hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL
  8. Congestive heart failure, New York Heart Association Class III or IV
  9. History of myocardial infarction, unstable angina, or revascularization within 6 months prior to screening.
  10. History of a cerebrovascular accident within 6 months prior to screening or with major neurological deficits
  11. Seizure disorder (other than with suspected or documented hypoglycemia).
  12. Active malignancy, except for basal or squamous cell skin cancers
  13. Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease)
  14. Major surgical operation within 30 days prior to screening
  15. Hematocrit ≤ 30%
  16. Bleeding disorder, treatment with warfarin, or platelet count < 50,000 /mm3
  17. Active alcohol abuse or substance abuse (per investigator assessment)
  18. Current chronic administration of oral or parenteral corticosteroids, however topical, intraarticular, and inhaled corticosteroids are allowed
  19. Use of an investigational drug within 15 days or 5 half-lives, whichever is longer, prior to screening
  20. Member of a special vulnerable populations such as pregnant women, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable
  21. Any other medical condition or finding that in the opinion of the investigator or sponsor, would compromise the safety of the subject or compromise the integrity of the study data
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Martin J Cummins 806-282-2120 mcummins@xerispharma.com
Contact: Khaled Junaidi, MD 312-517-1461 kjunaidi@xerispharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03770637
Other Study ID Numbers  ICMJE XSGR-PBH-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Xeris Pharmaceuticals
Study Sponsor  ICMJE Xeris Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Xeris Pharmaceuticals
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP