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

Phase 2

Completed

Conditions: Type 1 Diabetes

Interventions: Drug: Xeris glucagon
Drug: Lilly glucagon

Registration Number: NCT02018627

Lead Sponsor: Steven J. Russell, MD, PhD

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Xeris glucagon	Xeris glucagon	Xeris glucagon 50 micrograms, subcutaneous injection
Lilly glucagon	Lilly glucagon	Lilly glucagon 30 micrograms, subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Tmax	every 2 minutes for 1 hour post-dose of each glucagon	tmax for Xeris vs. Lilly (non-inferiority)

Secondary Outcome Measures

Name	Time	Method
GIRmin	every 2 minutes for 1 hour post-dose of each glucagon	Minimal glucose infusion rate (GIRmin) for Xeris vs. Lilly (non-inferiority)
Injection Pain	immediately after injection	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
Maximal Nausea	within 1 hour of injection	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
AOCGIR	every 2 minutes for 1 hour post-dose of each glucagon	Area over the curve for glucose infusion rate in the hour following administration (AOCGIR) for Xeris vs. Lilly (non-inferiority)
t½Max	every 2 minutes for 1 hour post-dose of each glucagon	Glucagon t½max for Xeris vs. Lilly (non-inferiority)
Injection Site Erythema	within 1 hour of injection	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
Dermal Response (Draize Scale Grade for Edema Formation)	within 1 hour of injection	Average grade on the edema formation portion of the Draize scale for dermal response (0 being the lowest, 4 being the highest)
Dermal Response (Draize Scale for Erythema and Eschar Formation)	within 1 hour of injection	Average grade on the erythema and eschar formation portion of the Draize scale for dermal response (0 being the lowest, 4 being the highest)