PK/PD Study With G-Pump (Glucagon Infusion) in T1DM Patients

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety, speed of absorption, and onset of action of G-Pump™ (glucagon infusion) at three subcutaneous doses as compared to Novo GlucaGen®, all delivered via an OmniPod® infusion pump to patients with type 1 diabetes.

Official Title
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Comparison of Pharmacokinetic and Pharmacodynamic Profiles of G-Pump™ (Glucagon Infusion) vs. GlucaGen® Delivered Subcutaneously to Subjects With Type 1 Diabetes (T1DM)

Conditions
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Hypoglycemia

Intervention / Treatment
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* Drug: Novo Nordisk GlucaGen®
* Drug: G-Pump™ (glucagon infusion)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females diagnosed with type 1 diabetes mellitus for at least 24 months Current usage of subcutaneous insulin pump treatment Age 18-65 years C-peptide level < 0.5 ng/ml Willingness to follow all study procedures, including attending all clinic visits Subject has provided informed consent and has signed and dated an informed consent form before any trial-related activities Exclusion Criteria: Pregnant and/ or Lactating: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study. HbA1c >10.0% Renal insufficiency (serum creatinine of 1.2 mg/dL or greater) Serum ALT or 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; or serum bilirubin of over 2.0. Hematocrit of less than or equal to 34% Congestive heart failure, NYHA class II, III or IV History of coronary artery disease Active foot ulceration History of a cerebrovascular accident Active alcohol abuse or substance abuse Active malignancy, except basal cell or squamous cell skin cancers Major surgical operation within 30 days prior to screening Seizure disorder Current administration of oral or parenteral corticosteroids Use of an investigational drug within 30 days prior to screening Bleeding disorder, treatment with warfarin, or platelet count below 50,000 Proliferative or severe non-proliferative retinopathy Gastroparesis Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease) Insulinoma Allergies to glucagon or glucagon-like products, or any history of significant hypersensitivity to glucagon or any related products. Glycogen storage disease Any concurrent illness, other than diabetes, that is not controlled by a stable therapeutic regimen Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Any reason the principal investigator deems exclusionary

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-Pump™ (glucagon infusion)<br>G-Pump™ (glucagon infusion); single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg | Drug: Novo Nordisk GlucaGen®<br>* single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg<br>Drug: G-Pump™ (glucagon infusion)<br>* single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg<br>|
| Active Comparator: Novo Nordisk GlucaGen®<br>Novo Nordisk GlucaGen®; single subcutaneous infusion doses 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg | Drug: Novo Nordisk GlucaGen®<br>* single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg<br>Drug: G-Pump™ (glucagon infusion)<br>* single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach 50% of Maximum Glucose Concentration (Glucose T50%-Early) | The onset of action was assessed by determining the time in minutes required to achieve 50% of the maximum plasma concentration of glucose following each dose of glucagon. | 0 to 150 minutes post-dosing | 
| Time to Reach 50% of Maximum Glucagon Concentration (Glucagon T50%-Early) | The speed of absorption was assessed by determining the time in minutes required to achieve 50% of the maximum plasma concentration of glucagon following each dose of glucagon. | 0 to 150 minutes post-dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon Cmax | Maximum plasma concentration of glucagon | From 0 to 150 minutes post-dosing | 
| Glucose Cmax | Maximum plasma concentration of glucose | From 0 to 150 minutes post-dosing | 
| Glucagon Tmax | Time to maximum plasma concentration of glucagon | From 0 to 150 minutes post-dosing | 
| Glucose Tmax | Time to maximum plasma concentration of glucose | From 0 to 150 minutes post-dosing | 
| Glucagon AUC | Area under the plasma concentration time curve for glucagon | From 0 to 150 minutes post-dosing | 
| Glucose AUC | Area under the plasma concentration time curve for glucose | From 0 to 150 minutes post-dosing | 
| Infusion Site Discomfort Score at 10 Minutes | Infusion site discomfort was assessed by the subjects using a 100 mm Visual Analog Scale (VAS) questionnaire at 10 minutes following the initiation of dosing. Subjects were asked to draw a vertical line across the horizontal scale to indicate their current level of discomfort from 0 = no discomfort to 100 = worst possible discomfort. The distance in mm from the left hand anchor to the the first point where the subject's mark crossed the horizontal scale was measured and reported as the infusion site discomfort score. | At 10 minutes post-dosing | 
| Infusion Site Discomfort Score at 30 Minutes | Infusion site discomfort was assessed by the subject using a 100 mm Visual Analog Scale (VAS) questionnaire at 30 minutes following the initiation of dosing. Subjects were asked to draw a vertical line across the horizontal scale to indicate their current level of discomfort from 0 = no discomfort to 100 = worst possible discomfort. The distance in mm from the left hand anchor to the the first point where the subject's mark crossed the horizontal scale was measured and reported as the infusion site discomfort score. | At 30 minutes post-dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoglycemia, Glucagon, Artificial Pancreas