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

Type 1 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02018627
• Other study ID #: 2013P002549
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 2014
• Est. completion date: August 2, 2018

Study information

• Verified date: September 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2, 2018
• Est. primary completion date: August 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Xeris glucagon
The subject is given an injection of xeris glucagon
• Lilly glucagon
The subject is given an injection of lilly glucagon

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Steven J. Russell, MD, PhD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tmax	tmax for Xeris vs. Lilly (non-inferiority)	every 2 minutes for 1 hour post-dose of each glucagon
Secondary	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
Secondary	GIRmin	Minimal glucose infusion rate (GIRmin) for Xeris vs. Lilly (non-inferiority)	every 2 minutes for 1 hour post-dose of each glucagon
Secondary	t½Max	Glucagon t½max for Xeris vs. Lilly (non-inferiority)	every 2 minutes for 1 hour post-dose of each glucagon
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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