Glucose Response of G-Pen (Glucagon Injection) in Pediatric T1D Patients

Study Overview
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Brief Summary
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This is a sequential efficacy and safety study in pediatric patients with type 1 diabetes. Subjects will be administered insulin to induce a low normal glycemic state and will then receive an age-appropriate dose of G-Pen (glucagon injection) in a clinical research center (CRC) or comparable setting.

Detailed Description
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This is an open-label, Phase 3 sequential efficacy and safety study in pediatric patients ages 2-17 with type 1 diabetes. Patients will complete the screening procedures up to 30 days before dosing to determine eligibility before enrollment to the treatment phase. The procedure to evaluate the efficacy of G-Pen (glucagon injection) consists of inducing a low normal glycemic state by administration of insulin. Subjects ages 2-11 will then be given a 0.5 mg dose of G-Pen, while subjects ages 12-17 will receive a 1 mg dose of G-Pen. Subjects ages 12-17 will return for a second visit 1-4 weeks later and will receive a 0.5 mg dose of G-Pen when in a low normal glycemic stare. Plasma glucose and glucagon levels will be monitored for 90 and 180 minutes post-dosing, respectively, at all visits. A follow-up phone call as a safety check will be conducted 3 - 14 days following administration of the final dose.

Official Title
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A Phase 3 Study to Evaluate the Glucose Response of G-Pen (Glucagon Injection) in Pediatric Patients With Type 1 Diabetes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Glucagon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with T1D for at least 6 months at Screening. current usage of daily insulin treatment. Exclusion Criteria: pregnant or nursing 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 venous access current seizure disorder history of pheochromocytoma or disorder with increased risk of pheochromocytoma history of insulinoma history of glycogen storage disease. active use of alcohol or drugs of abuse administration of glucagon within 14 days of the first treatment visit participation in other studies involving an investigational drug or device within 30 days

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-Pen (glucagon injection) 0.5 mg<br>A single 0.5 mg subcutaneous (SC) injection of G-Pen (glucagon injection) | Drug: Glucagon<br>* 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector<br>* Other names: G-Pen (glucagon injection);|
| Experimental: G-Pen (glucagon injection) 1.0 mg<br>A single 1.0 mg subcutaneous (SC) injection of G-Pen (glucagon injection) | Drug: Glucagon<br>* 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector<br>* Other names: G-Pen (glucagon injection);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Glucose | The primary endpoint for this study is an evaluation of change in plasma glucose following treatment with G-Pen, with an emphasis on the increase from baseline to 30 minutes post-dosing. | 0-30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time for Plasma Glucose to Increase by ≥25 mg/dL | Time for plasma glucose to increase by ≥25 mg/dL from baseline will be analyzed descriptively for each age cohort. | 0-90 minutes | 
| Plasma Glucagon Area Under the Curve | Plasma glucagon area under the curve (AUC) for each age cohort will be analyzed descriptively. | 0-90 minutes | 
| Plasma Glucagon Cmax | Plasma glucagon maximum concentration for each age cohort will be analyzed descriptively. | 0-180 minutes | 
| Plasma Glucagon Tmax | Plasma glucagon time to maximum concentration for each age cohort will be analyzed descriptively. | 0-180 minutes |