Clinical Trials

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 PBH by a physician, requiring intervention such as intake of oral carbohydrates. This diagnosis includes documentation of endogenous hyperinsulinismin 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) ≤ 40kg/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 agreeto use contraception and refrain from breast-feeding during the study and for at least 15 days after participating in the study. Acceptable contraception includes birth control pill/patch/vaginal ring, Depo-Provera® (medroxyprogesterone acetate), Norplant® System (levonorgestrel), IUD, double-barrier method (woman uses a diaphragm and spermicide and man uses a condom), or abstinence. There is no contraception required for males.

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.