G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes

Study Overview
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Brief Summary
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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.

Official Title
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G-Pen (Glucagon Injection) Compared to GlucaGen® Hypokit® (Glucagon) for Induced Hypoglycemia Rescue in Adults With T1D: A Phase 3 Multi-center, Randomized, Controlled, Single Blind, 2-way Crossover Study to Evaluate Efficacy and Safety

Conditions
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Insulin Hypoglycemia, Type 1 Diabetes Mellitus, Severe Hypoglycemia

Intervention / Treatment
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* Drug: G-Pen
* Drug: Novo Glucagon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months. Current usage of daily insulin treatment that includes having an assigned correction factor for managing hyperglycemia. Age 18 to 75 years, inclusive. Random serum C-peptide concentration < 0.6 ng/mL. Willingness to follow all study procedures, including attending all clinic visits. 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: Pregnancy Glycated hemoglobin (HbA1c) > 10% at Screening. Body mass index (BMI) > 40 kg/m2. Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or greater than 3 times the upper limit of normal. Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL. Hematocrit < 30%. 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. Clinically significant electrocardiogram (ECG) abnormalities. Use of total insulin dose per day > 2 U/kg. Inadequate venous access. Congestive heart failure, New York Heart Association (NYHA) class III or IV. History of myocardial infarction, unstable angina, or revascularization within the past 6 months. History of a cerebrovascular accident in the past 6 months or with major neurological deficits. 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. Major surgical operation within 30 days prior to Screening. Current seizure disorder (other than with suspect or documented hypoglycemia). Current bleeding disorder, treatment with warfarin, or platelet count below 50 × 109 per liter. History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis, or Von Hippel-Lindau disease). History of insulinoma. 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. History of glycogen storage disease. 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. 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). Administration of glucagon within 7 days of Screening. 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. Any other reason the Investigator deems exclusionary.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-Pen followed by Novo Glucagon<br>1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit | Drug: G-Pen<br>* 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector<br>* Other names: glucagon;Drug: Novo Glucagon<br>* 1 mg subcutaneous injection of Novo Glucagon (glucagon injection)<br>* Other names: Glucagen Hypokit;|
| Active Comparator: Novo Glucagon followed by G-Pen<br>1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit | Drug: G-Pen<br>* 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector<br>* Other names: glucagon;Drug: Novo Glucagon<br>* 1 mg subcutaneous injection of Novo Glucagon (glucagon injection)<br>* Other names: Glucagen Hypokit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Hypoglycemia Rescue | Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration > 20 mg/dL (> 1.11 mmol/L) within 30 minutes after administration of glucagon | At 30 minutes following administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Glucose Response 1 | Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) within 30 minutes of a decision to dose | At 30 minutes following a decision to administer study drug | 
| Plasma Glucose Response 2 | Number of subjects with an increase in plasma glucose concentration > 20 mg/dL (> 1.11 mmol/L) after administration of glucagon. | At 0-30 minutes following a decision to administer study drug | 
| Administration Time | Mean time (minutes) to administer study drug from a decision to dose | At 0-10 minutes from a decision to administer study drug | 
| Hypoglycemia Resolution | Mean time (minutes) to complete resolution of the overall sensation of hypoglycemia from a decision to dose | At 0-90 minutes following administration of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucagon, hypoglycemia