Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics

This is a blinded, randomized, Phase 3 comparative efficacy and safety study in adults with
type 1 diabetes. Patients will complete screening procedures up to 60 days before
randomization to determine eligibility before enrollment to the treatment phase.

The procedure for evaluating the efficacy of the G-Pen (glucagon injection) consists of
inducing hypoglycemia by intravenous administration of regular insulin diluted in normal
saline. Each participant will undergo two episodes of insulin-induced hypoglycemia, and in
random order will receive 1 mg G-Pen (glucagon injection) during one episode and 1 mg Lilly
Glucagon during the other episode. There will be wash out period of 7-28 days between
treatment visits.

Blood glucose levels will be monitored post-dosing, with a return of plasma glucose to a
concentration > 70 mg/dL within 30 minutes signifying successful hypoglycemia rescue. As a
confirmation of efficacy, subjects will complete a questionnaire concerning changes in
symptoms of hypoglycemia following treatment with glucagon.

Subjects will return for a follow-up safety visit 3-14 days following administration of the
final dose of glucagon.

Inclusion Criteria:

- diagnosed with type 1 diabetes mellitus for at least 24 months

- usage of daily insulin treatment

- random serum C-peptide concentration < 0.5 ng/mL

Exclusion Criteria:

- pregnant or nursing

- HbA1c >9.0%

- renal insufficiency

- hepatic synthetic insufficiency

- aspartate or alanine aminotransferase > 3 times the upper limit of normal

- hematocrit less than or equal to 30%

- use of > 2.0 U/kg total insulin dose per day

- inadequate bilateral venous access in both arms

- congestive heart failure, New York Heart Association class II, III or IV

- active malignancy within 5 years, except basal cell or squamous cell skin cancers

- history of breast cancer or malignant melanoma

- major surgical operation within 30 days

- current seizure disorder.

- current bleeding disorder, treatment with warfarin, or platelet count below 50,000

- history of pheochromocytoma or disorder with increased risk of pheochromocytoma

- history of insulinoma

- history of glycogen storage disease.

- positive for HIV, hepatitis C virus or active hepatitis B virus infection

- whole blood donation of 1 pint (500 mL) within 8 weeks

- active substance or alcohol abuse

- administration of glucagon within 28 days

- participation in other studies involving an investigational drug or device within 30
days