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

Inclusion criteria

• 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.

Exclusion criteria

• 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%
• Bleeding disorder, treatment with warfarin, or platelet count < 50,000 /mm3
• Active alcohol abuse or substance abuse (per investigator assessment)
• Current chronic administration of oral or parenteral corticosteroids, however topical, intraarticular, and inhaled corticosteroids are allowed
• Use of an investigational drug within 15 days or 5 half-lives, whichever is longer, prior to screening
• Member of a special vulnerable populations such as pregnant women, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable
• 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