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:

1. Age 18-55 years, inclusive

2. BMI ≥27 to ≤40 kg/m2

3. Stable body weight for 3 months (self-reported loss/gain <5%)

4. Subject is judged to be non-diabetic and in good health on the basis of medical
history, physical examination, electrocardiogram, and routine laboratory data

5. 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

6. Subject is willing to avoid alcohol consumption for 48 hours prior to the inpatient
study visit

7. Subject is willing to avoid consumption of caffeine and caffeinated beverages for 24
hours prior to the inpatient study visit

8. Subject is willing to avoid strenuous physical activity for 72 hours prior to the
inpatient study visit

9. 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:

1. 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)

2. History of bariatric surgery

3. Current liver, renal, pulmonary, cardiac, oncologic, metabolic, gastrointestinal or
hematologic disease which the Investigator believes is clinically significant,
including:

1. 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

2. 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

3. 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)

4. 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

5. History of irritable bowel disease, recurrent nausea or vomiting

6. Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women)

4. Self-reported history of hepatitis B, hepatitis C, or HIV

5. 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.)

6. Diagnosis of sleep apnea with or without use of (continuous positive airway pressure)

7. Major surgery within last 3 months

8. Blood donation within 4 weeks prior to the screening visit

9. 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.

10. Illicit drug abuse or use of nicotine-containing products within 3 months prior to the
screening visit

11. Poor intravenous access

12. Blood pressure less than 100/50 mm Hg or greater than or equal to 160/100 mm Hg at
screening visit

13. Heart rate greater than or equal to 100 beats/min at screening visit

14. Fasting plasma glucose <60 mg/dL or ≥126 mg/dL at screening visit

15. Translational Research Institute (TRI) staff member or immediate relative of TRI staff
member, directly involved with this study

16. 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