Glucagon Ready-to-Use for the Prevention of Exercise-Induced Hypoglycemia During Aerobic Exercise in Adults With T1D
Glucagon Ready-to-Use for the Prevention of Exercise-Induced Hypoglycemia During Aerobic Exercise in Adults With T1D
This study is a randomized, placebo-controlled, double-blind, two-treatment, two-period,
 crossover comparison in a clinical research center (CRC) setting, followed by a randomized,
 placebo-controlled, partially double-blinded, 3-arm parallel comparison in an outpatient
 setting to evaluate the preliminary efficacy and safety of Glucagon Ready-to-Use (RTU) to
 prevent exercise-induced hypoglycemia (EIH) in adults with Type 1 diabetes mellitus (T1D),
 who perform regular, moderate-to-high intensity aerobic exercise.
Inclusion Criteria:

 1. Clinical diagnosis of presumed autoimmune type 1 diabetes, receiving daily insulin via
 continuous subcutaneous insulin infusion.

 2. Age 18 to < 65 years.

 3. Duration of type 1 diabetes ≥ 2 years.

 4. Random C-peptide < 0.6 ng/mL.

 5. Using insulin therapy by continuous subcutaneous insulin infusion pump for at least 6
 months.

 6. History of exercise-related hypoglycemia.

 7. Performs aerobic exercise regularly (2-3 times per week), and desires to exercise per
 American Diabetes Association guidelines (150 minutes per week). Examples of aerobic
 exercise include: power walking, hiking, running/jogging, cycling, swimming, cross
 country skiing, and aerobic fitness classes.

 8. Will abstain from the use of non-insulin diabetes therapies such as sodium glucose
 co-transporter 2, glucagon like peptide-1, and metformin for the duration of the
 study.

 9. Subject must be willing to adhere to the protocol requirements for the duration of the
 study.

 10. Subject has provided informed consent as evidenced by a signed/dated informed consent
 form completed before any trial-related activities occur.

 Exclusion Criteria:

 1. Frequently experience hyperglycemia with exercise, in the clinical judgement of the
 investigator.

 2. Pregnant and/ or Nursing: For female subjects of childbearing potential, there is a
 requirement for a negative urine pregnancy test and for agreement to use contraception
 and to refrain from breast feeding during the study, and for at least 1 week after the
 last dose of study drug. Acceptable contraception includes birth control pill / patch
 / vaginal ring, Depo-Provera, Norplant, an intra-uterine device, the double barrier
 method (the woman uses a diaphragm and spermicide and the man uses a condom), or
 abstinence.

 3. One or more severe hypoglycemic episodes in the past 12 months (as defined by an
 episode that required third party assistance for treatment).

 4. Uses inhaled insulin.

 5. Hemoglobin A1c > 9.0% at Screening.

 6. Renal insufficiency (serum creatinine greater than 3 mg/dL (0.17 mmol/L)).

 7. Serum alanine aminotransferase or aspartate aminotransferase equal to or greater than
 3 times the upper limit of normal.

 8. Hepatic synthetic insufficiency as defined as a serum albumin of less than 3 mg/dL
 (0.17 mmol/L); or serum bilirubin greater than 2 mg/dL (0.11 mmol/L).

 9. Hematocrit of less than or equal to 30%.

 10. Mean of triplicate blood pressure (BP) readings at Screening where systolic BP <90 or
 >150 mm Hg, or diastolic BP <50 or >100 mm Hg.

 11. Clinically significant electrocardiogram abnormalities.

 12. Use of > 2.0 U/kg total insulin dose per day.

 13. Inadequate bilateral venous access in both arms.

 14. Congestive heart failure, New York Heart Association class III or IV.

 15. Active malignancy within 5 years from Screening, except basal cell or squamous cell
 skin cancers.

 16. Major surgical operation within 90 days prior to screening, or planned surgical
 operation during the study.

 17. History of seizure disorders.

 18. Current bleeding disorder, treatment with warfarin or any anticoagulants, or platelet
 count below 50,000.

 19. History of pheochromocytoma or disorder with increased risk of pheochromocytoma
 (multiple endocrine neoplasia type 2, neurofibromatosis, or Von Hippel-Lindau
 disease).

 20. History of insulinoma.

 21. History of allergies to glucagon or glucagon-like products, or any history of
 significant hypersensitivity to glucagon or any related products or to any of the
 excipients (dimethylsulfoxide, mannitol, & trehalose) in the investigational
 formulation.

 22. History of glycogen storage disease.

 23. Subject tests positive for human immunodeficiency virus, hepatitis C virus, or active
 hepatitis B virus infection at Screening.

 24. Any concurrent illness, other than diabetes, that is not controlled by a stable
 therapeutic regimen.

 25. Active substance or alcohol abuse, in the opinion of the investigator. Subjects
 reporting active marijuana use or testing positive for tetrahydrocannabinol via rapid
 urine test will be allowed to participate in the study at the discretion of the
 investigator.

 26. Participation in other studies involving administration of an investigational
 therapeutic agent (drug or device) within 30 days or 5 half-lives, whichever is
 longer, before Screening for the current study and during participation in the current
 study.

 27. Any reason the investigator deems exclusionary.