Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon

Study Overview
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Brief Summary
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This study will test the hypothesis that micro-doses of Xerisol Glucagon (Xeris Pharmaceuticals) will be non-inferior by pharmacokinetic and pharmacodynamic criteria vs. micro-doses of Glucagon for Injection (Eli Lilly).

Detailed Description
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This study will test the hypothesis that micro-doses of a new formulation of stable glucagon, Xerisol Glucagon (Xeris Pharmaceuticals), will be non-inferior by pharmacokinetic and pharmacodynamic criteria vs. micro-doses of a freshly reconstituted formulation of glucagon that has poor stability in solution, Glucagon for Injection (Eli Lilly).

Official Title
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Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Xeris glucagon
* Drug: Lilly glucagon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21 to 80 years old with type 1 diabetes for at least one year. Diabetes managed using an insulin infusion pump using rapid-acting insulin such as insulin aspart (NovoLog), insulin lispro (Humalog), and insulin glulisine (Apidra) for at least one week prior to enrollment. Exclusion Criteria: Unable to provide informed consent. Unable to comply with study procedures. Current participation in another diabetes-related clinical trial that, in the judgment of the principle investigator, will compromise the results of the clamp study or the safety of the subject. Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception. End stage renal disease on dialysis (hemodialysis or peritoneal dialysis). Hemoglobin < 11.5 gm/dl. History of pheochromocytoma. Fractionated metanephrines will be tested in patients with history increasing the risk for a catecholamine secreting tumor (paroxysms of tachycardia, pallor, or headache; personal or family history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease; episodic or treatment of refractory hypertension, defined as requiring 4 or more medications to achieve normotension). History of adverse reaction to glucagon (including allergy) besides nausea, vomiting, or headache. Inadequate venous access as determined by study nurse or physician at time of screening. Liver failure or cirrhosis. Any other factors that, in the judgment of the principal investigator, would interfere with the safe completion of the study procedures.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xeris glucagon<br>Xeris glucagon 50 micrograms, subcutaneous injection | Drug: Xeris glucagon<br>* The subject is given an injection of xeris glucagon<br>|
| Active Comparator: Lilly glucagon<br>Lilly glucagon 30 micrograms, subcutaneous injection | Drug: Lilly glucagon<br>* The subject is given an injection of lilly glucagon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | tmax for Xeris vs. Lilly (non-inferiority) | every 2 minutes for 1 hour post-dose of each glucagon | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AOCGIR | Area over the curve for glucose infusion rate in the hour following administration (AOCGIR) for Xeris vs. Lilly (non-inferiority) | every 2 minutes for 1 hour post-dose of each glucagon | 
| GIRmin | Minimal glucose infusion rate (GIRmin) for Xeris vs. Lilly (non-inferiority) | every 2 minutes for 1 hour post-dose of each glucagon | 
| t½Max | Glucagon t½max for Xeris vs. Lilly (non-inferiority) | every 2 minutes for 1 hour post-dose of each glucagon | 
| Injection Pain | Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly: -average Injection pain on a 10 cm standard VAS: 0 = no pain, 10 = worst imaginable pain reported immediately after injection of glucagon | immediately after injection | 
| Injection Site Erythema | Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly: -Injection site erythema or other local reaction, maximum diameter within 1 hour of injection | within 1 hour of injection | 
| Maximal Nausea | Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly: -Maximal nausea within 1 hour of injection on a 10 cm VAS: no nausea = 0, vomiting = 10 | within 1 hour of injection | 
| Dermal Response (Draize Scale for Erythema and Eschar Formation) | Average grade on the erythema and eschar formation portion of the Draize scale for dermal response (0 being the lowest, 4 being the highest) | within 1 hour of injection | 
| Dermal Response (Draize Scale Grade for Edema Formation) | Average grade on the edema formation portion of the Draize scale for dermal response (0 being the lowest, 4 being the highest) | within 1 hour of injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bionic pancreas, artificial pancreas, insulin, glucagon, clamp