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

NCT03770637 | Completed Phase 2 FDA Drug

• 1 other identifier: XSGR-PBH-201
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

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.

Conditions

Hyperinsulinemic Hypoglycemia

Keywords

glucagon; post-bariatric hypoglycemia

Outcome Measures

Primary Outcomes (2)

• Blood glucose recovery: CRC

  Number of subjects with blood glucose \> 70 mg/dL

  At 15 minutes following administration of study drug

• Blood glucose recovery: Out-patient

  Frequency of blood glucose \> 70 mg/dL

  At 15 minutes following administration of study drug

Secondary Outcomes (7)

• Symptomatic Recovery: CRC

  At 15, 30, and 60 minutes following administration of study drug

• Incidence of severe hypoglycemia: CRC

  At 0-240 minutes following administration of study drug

• Incidence of severe hypoglycemia: Out-patient

  During 12 weeks of out-patient treatment

• Incidence of serious hypoglycemia: CRC

  At 0-240 minutes following administration of study drug

• Incidence of serious hypoglycemia: Out-patient

  During 12 weeks of out-patient treatment

Study Arms (2)

Glucagon RTU (glucagon injection)

EXPERIMENTAL

Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon)

Drug: Glucagon RTU

Placebo

PLACEBO COMPARATOR

Non-active vehicle for Glucagon RTU; 60 μL injection

Other: Placebo

Interventions

Glucagon RTU DRUG

Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe.

Also known as: glucagon

Glucagon RTU (glucagon injection)

Placebo OTHER

The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle).

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• Aged 18 to 75 years of age, inclusive
• Symptoms of hypoglycemia that developed after bariatric surgery (Roux-en-Y gastric bypass \[RYGB\] only) in the absence of antidiabetic medications
• History of bariatric surgery (RYGB only), at least 6 months prior to screening
• Whipple's triad
• Ability to both experience and recognize hypoglycemic awareness.
• Documented glucose levels \< 54 mg/dL when experiencing symptoms suggestive of hypoglycemia
• Relief of hypoglycemia symptoms when the glucose is raised to normal
• 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.
• 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.
• Body mass index (BMI) ≤ 40 kg/m2
• Willingness to follow all study procedures, including attending all clinic visits and self-administering blinded study drug at home for 12 weeks
• 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
• 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.

You may not qualify if:

• Documented hypoglycemia occurring in the fasting state (\> 12 hours fast) within 12 months of study entry
• Hypoglycemic unawareness as evidenced by a Gold Scale score \> 4 at screening
• Early Dumping Syndrome
• Known insulinoma or adrenal insufficiency
• Active treatment with any insulin/insulin secretagogues, or other diabetes medications except for acarbose and glucagon-like peptide 1 (GLP-1) analogues
• Chronic kidney disease Stage 4 or 5 or an estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73 m2 at screening
• 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
• Congestive heart failure, New York Heart Association Class III or IV
• History of myocardial infarction, unstable angina, or revascularization within 6 months prior to screening.
• History of a cerebrovascular accident within 6 months prior to screening or with major neurological deficits
• Seizure disorder (other than with suspected or documented hypoglycemia).
• Active malignancy, except for basal or squamous cell skin cancers
• Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease)
• Major surgical operation within 30 days prior to screening
• Hematocrit ≤ 30%

Sponsors & Collaborators

• Xeris Pharmaceuticals: lead

Study Sites (5)

University of Colorado-Denver

Aurora, Colorado, 80045, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic- Rochester

Rochester, Minnesota, 55905, United States

Location

Duke Early Phase Clinical Research

Durham, North Carolina, 27701, United States

Location

MeSH Terms

Conditions

Congenital Hyperinsulinism

Interventions

Glucagon

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hypoglycemia

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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..

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: December 10, 2018
• Study Start: May 10, 2019
• Primary Completion: February 26, 2020
• Study Completion: February 26, 2020
• Last Updated: May 21, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)