G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes
Condition: Insulin Hypoglycemia; Type 1 Diabetes Mellitus; Severe Hypoglycemia
MeSH terms: Diabetes Mellitus, Type 1; Hypoglycemia
Intervention: G-Pen; Novo Glucagon
Intervention description: 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector; 1 mg subcutaneous injection of Novo Glucagon (glucagon injection)
Intervention MeSH terms: Glucagon; Glucagon-Like Peptide 1
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Enrollment: 132.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: glucagon; hypoglycemia

Summary:

      This is a multi-center, randomized, controlled, single-blind, two-way crossover efficacy and
      safety study in subjects with Type 1 diabetes mellitus. The study involves two daytime
      clinical research center (CRC) visits with random assignment to receive G-Pen glucagon 1 mg
      during one period and Novo Glucagon 1 mg during the other. Each daytime visit is preceded by
      an overnight stay in the CRC. In the morning of the inpatient study visit, the subject is
      brought into a state of severe hypoglycemia through IV administration of regular insulin
      diluted in normal saline. After a hypoglycemic state with plasma glucose < 54 mg/dL (3
      mmol/L) is verified, the subject is administered a dose of G-Pen or Novo Glucagon via
      subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes
      post-dosing, with a value of >70.0 mg/dL (3.89 mmol/L) or an increase of > 20 mg/dL (>1.11
      mmol/L) within 30 minutes of glucagon administration indicating a positive response. After 3
      hours, the subject is given a meal and discharged when medically stable. After a wash-out
      period of 7 to 28 days, subjects return to the CRC, and the procedures are repeated with each
      subject crossed over to the other treatment. A follow-up visit as a safety check is conducted
      2-7 days following administration of the final dose of study drug.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24
             months.

          2. Current usage of daily insulin treatment that includes having an assigned "correction
             factor" for managing hyperglycemia.

          3. Age 18 to 75 years, inclusive.

          4. Random serum C-peptide concentration < 0.6 ng/mL.

          5. Willingness to follow all study procedures, including attending all clinic visits.

          6. Subject has provided informed consent as evidenced by a signed and dated informed
             consent form (ICF) completed before any trial-related activities occur.

        Exclusion Criteria:

          1. Pregnancy

          2. Glycated hemoglobin (HbA1c) > 10% at Screening.

          3. Body mass index (BMI) > 40 kg/m2.

          4. Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal
             disease requiring renal replacement therapy.

          5. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or
             greater than 3 times the upper limit of normal.

          6. Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL.

          7. Hematocrit < 30%.

          8. Blood pressure (BP) readings at Screening where systolic blood pressure (SBP) < 90 or
             > 150 mm Hg, and diastolic blood pressure (DBP) < 50 or > 100 mm Hg.

          9. Clinically significant electrocardiogram (ECG) abnormalities.

         10. Use of total insulin dose per day > 2 U/kg.

         11. Inadequate venous access.

         12. Congestive heart failure, New York Heart Association (NYHA) class III or IV.

         13. History of myocardial infarction, unstable angina, or revascularization within the
             past 6 months.

         14. History of a cerebrovascular accident in the past 6 months or with major neurological
             deficits.

         15. Active malignancy within 5 years from Screening, except basal cell or squamous cell
             skin cancers. Any history of breast cancer or malignant melanoma will be exclusionary.

         16. Major surgical operation within 30 days prior to Screening.

         17. Current seizure disorder (other than with suspect or documented hypoglycemia).

         18. Current bleeding disorder, treatment with warfarin, or platelet count below 50 × 109
             per liter.

         19. History of pheochromocytoma or disorder with increased risk of pheochromocytoma
             (multiple endocrine neoplasia type 2 (MEN 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 (DMSO and trehalose) in the investigational formulation.

         22. History of glycogen storage disease.

         23. Subject tests positive for human immunodeficiency virus (HIV), hepatitis C virus
             (HCV), or hepatitis B virus (HBV) infection (hepatitis B surface antigen positive
             [HBsAg+]) at Screening.

         24. Active substance other than tetrahydrocannabinol (THC) or alcohol abuse (more than 21
             drinks per week for male subjects or 14 drinks per week for female subject).

         25. Administration of glucagon within 7 days of Screening.

         26. Participation in other studies involving administration of an investigational 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 other reason the Investigator deems exclusionary.