Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon

This study will test the hypothesis that micro-doses of a new formulation of stable glucagon,
Xerisol Glucagon (Xeris Pharmaceuticals), will be non-inferior by pharmacokinetic and
pharmacodynamic criteria vs. micro-doses of a freshly reconstituted formulation of glucagon
that has poor stability in solution, Glucagon for Injection (Eli Lilly).

Inclusion Criteria:

- Age 21 to 80 years old with type 1 diabetes for at least one year.

- Diabetes managed using an insulin infusion pump using rapid-acting insulin such as
insulin aspart (NovoLog), insulin lispro (Humalog), and insulin glulisine (Apidra) for
at least one week prior to enrollment.

Exclusion Criteria:

- Unable to provide informed consent.

- Unable to comply with study procedures.

- Current participation in another diabetes-related clinical trial that, in the judgment
of the principle investigator, will compromise the results of the clamp study or the
safety of the subject.

- Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the
immediate future, or sexually active without use of contraception.

- End stage renal disease on dialysis (hemodialysis or peritoneal dialysis).

- Hemoglobin < 11.5 gm/dl.

- History of pheochromocytoma. Fractionated metanephrines will be tested in patients
with history increasing the risk for a catecholamine secreting tumor (paroxysms of
tachycardia, pallor, or headache; personal or family history of MEN 2A, MEN 2B,
neurofibromatosis, or von Hippel-Lindau disease; episodic or treatment of refractory
hypertension, defined as requiring 4 or more medications to achieve normotension).

- History of adverse reaction to glucagon (including allergy) besides nausea, vomiting,
or headache.

- Inadequate venous access as determined by study nurse or physician at time of
screening.

- Liver failure or cirrhosis.

- Any other factors that, in the judgment of the principal investigator, would interfere
with the safe completion of the study procedures.