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

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).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Xeris glucagon; Drug: Lilly glucagon

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).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Steven J. Russell, MD, PhD

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): August 2, 2018
• Study Completion (Actual): August 2, 2018

Study Registration Dates

• First Submitted: December 16, 2013
• First Submitted That Met QC Criteria: December 17, 2013
• First Posted (Estimate): December 23, 2013

Study Record Updates

• Last Update Posted (Actual): October 8, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: glucagon; artificial pancreas; insulin; bionic pancreas; clamp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: 2013P002549

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No