To Determine Tolerability to Glucagon Infusion in Obese Subjects

To determine the tolerability of glucagon infusion administered in an escalating step-wise manner in healthy obese subjects

Inclusion criteria

• Age 18-55 years, inclusive
• BMI ≥27 to ≤40 kg/m2
• Stable body weight for 3 months (self-reported loss/gain <5%)
• Subject is judged to be non-diabetic and in good health on the basis of medical history, physical examination, electrocardiogram, and routine laboratory data
• Subject understands the procedures and agrees to participate in the study program by giving written informed consent, and is willing to comply with the trial restrictions
• Subject is willing to avoid alcohol consumption for 48 hours prior to the inpatient study visit
• Subject is willing to avoid consumption of caffeine and caffeinated beverages for 24 hours prior to the inpatient study visit
• Subject is willing to avoid strenuous physical activity for 72 hours prior to the inpatient study visit
• Female subjects of child bearing potential must be willing to use acceptable birth control during study participation (oral contraceptives, intrauterine device, implanted or injectable contraceptives, abstinence).

Exclusion criteria

• Treatment with any medication known to significantly impact body weight (e.g., weight loss medications, atypical antipsychotics) within 3 months prior to screening except for stable physiological hormone replacement therapy (i.e., thyroid hormone, estrogen)
• History of bariatric surgery
• Current liver, renal, pulmonary, cardiac, oncologic, metabolic, gastrointestinal or hematologic disease which the Investigator believes is clinically significant, including:

• Liver disease or liver injury as indicated by abnormal liver function tests (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase , serum bilirubin) >3 × upper limit of normal (ULN), or history of hepatic cirrhosis
• History or presence of impaired renal function as indicated by an estimated glomerular filtration rate <60 ml/hr or urine albumin-to-creatinine ratio >35 mg/mmol
• Significant cardiovascular disease, including Class III or greater congestive heart failure (CHF), coronary artery disease, second degree or greater heart block, or clinically significant arrhythmias; baseline second degree or greater heart block or prolonged QT syndrome (QTc interval ≥ 470 msec); or any major cardiovascular event within the last 3 years (including myocardial infarction, transient ischemic attack [TIA], cerebrovascular accident [CVA], angina, and hospitalization due to CHF, transient ischemic attack (TIA), and CVA)
• Metabolic, other or endocrine disorders, including diagnosis of type 1 or type 2 diabetes mellitus [HbA1c ≥6.5%]), inadequately treated hyperthyroidism (thyroid stimulating hormone [TSH] below normal range) or hypothyroidism (TSH above upper limit of normal if symptomatic or TSH >10 U/mL), Cushing syndrome, Addison's disease, hypogonadism, or genetic disorders linked to obesity
• History of irritable bowel disease, recurrent nausea or vomiting
• Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women)
• Self-reported history of hepatitis B, hepatitis C, or HIV
• History of recurrent sleep disturbances and/or prone to sleep disturbances based on lifestyle or employment (e.g., variable work schedule, overnight shift work, etc.)
• Diagnosis of sleep apnea with or without use of (continuous positive airway pressure)
• Major surgery within last 3 months
• Blood donation within 4 weeks prior to the screening visit
• Participation in another investigational trial within 4 weeks prior to the screening visit. The 4 week window will be derived from the date of the last trial medication and/or blood collection in a previous trial and/or adverse event (AE) related to trial drug to the screening visit of the current trial.
• Illicit drug abuse or use of nicotine-containing products within 3 months prior to the screening visit
• Poor intravenous access
• Blood pressure less than 100/50 mm Hg or greater than or equal to 160/100 mm Hg at screening visit
• Heart rate greater than or equal to 100 beats/min at screening visit
• Fasting plasma glucose <60 mg/dL or ≥126 mg/dL at screening visit
• Translational Research Institute (TRI) staff member or immediate relative of TRI staff member, directly involved with this study
• History of any illness or condition that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by study participation