Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics

G-Pen (Glucagon Injection) Compared to Lilly Glucagon (Glucagon for Injection [RDNA Origin]) for Induced Hypoglycemia Rescue in Adult Patients With T1DM: A Phase 3, Multi-center, Randomized, Blinded, 2-Way Crossover Study to Evaluate Efficacy and Safety

This is a blinded, randomized crossover study to compare the safety and efficacy of G-Pen (glucagon injection) to Lilly Glucagon (glucagon for injection [rDNA origin]) for hypoglycemia rescue of adult patients with type 1 diabetes.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: G-Pen (glucagon injection); Drug: Lilly Glucagon (glucagon injection [rDNA origin])

Detailed Description

This is a blinded, randomized, Phase 3 comparative efficacy and safety study in adults with type 1 diabetes. Patients will complete screening procedures up to 60 days before randomization to determine eligibility before enrollment to the treatment phase.

The procedure for evaluating the efficacy of the G-Pen (glucagon injection) consists of inducing hypoglycemia by intravenous administration of regular insulin diluted in normal saline. Each participant will undergo two episodes of insulin-induced hypoglycemia, and in random order will receive 1 mg G-Pen (glucagon injection) during one episode and 1 mg Lilly Glucagon during the other episode. There will be wash out period of 7-28 days between treatment visits.

Blood glucose levels will be monitored post-dosing, with a return of plasma glucose to a concentration > 70 mg/dL within 30 minutes signifying successful hypoglycemia rescue. As a confirmation of efficacy, subjects will complete a questionnaire concerning changes in symptoms of hypoglycemia following treatment with glucagon.

Subjects will return for a follow-up safety visit 3-14 days following administration of the final dose of glucagon.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Diabetes & Endocrinology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Chula Vista, California, United States, 91911
      • ProSciento, Inc.
    • Escondido, California, United States, 92025
      • AMCR Institute
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosed with type 1 diabetes mellitus for at least 24 months
• usage of daily insulin treatment
• random serum C-peptide concentration < 0.5 ng/mL

Exclusion Criteria:

• pregnant or nursing
• HbA1c >9.0%
• renal insufficiency
• hepatic synthetic insufficiency
• aspartate or alanine aminotransferase > 3 times the upper limit of normal
• hematocrit less than or equal to 30%
• use of > 2.0 U/kg total insulin dose per day
• inadequate bilateral venous access in both arms
• congestive heart failure, New York Heart Association class II, III or IV
• active malignancy within 5 years, except basal cell or squamous cell skin cancers
• history of breast cancer or malignant melanoma
• major surgical operation within 30 days
• current seizure disorder.
• current bleeding disorder, treatment with warfarin, or platelet count below 50,000
• history of pheochromocytoma or disorder with increased risk of pheochromocytoma
• history of insulinoma
• history of glycogen storage disease.
• positive for HIV, hepatitis C virus or active hepatitis B virus infection
• whole blood donation of 1 pint (500 mL) within 8 weeks
• active substance or alcohol abuse
• administration of glucagon within 28 days
• participation in other studies involving an investigational drug or device within 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: G-Pen first, then Lilly Glucagon; A single 1 mg subcutaneous (SC) injection of G-Pen (glucagon injection) with a 7-28 day wash-out, followed by a single 1 mg SC injection of Lilly Glucagon (glucagon injection [rDNA origin])	Drug: G-Pen (glucagon injection); 1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector; Other Names: glucagon; Drug: Lilly Glucagon (glucagon injection [rDNA origin]); 1 mg of Lilly glucagon reconstituted from lyophilized powder; Other Names: glucagon
Other: Lilly Glucagon first, then G-Pen; A single 1 mg SC injection of Lilly Glucagon (glucagon injection [rDNA origin]) with a 7-28 day wash-out, followed by a single 1 mg SC injection of G-Pen (glucagon injection)	Drug: G-Pen (glucagon injection); 1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector; Other Names: glucagon; Drug: Lilly Glucagon (glucagon injection [rDNA origin]); 1 mg of Lilly glucagon reconstituted from lyophilized powder; Other Names: glucagon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoglycemia Rescue: Intent-to-Treat Population	Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon	At 30 minutes following administration of study drug
Hypoglycemia Rescue: Per Protocol Population	Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon	At 30 minutes following administration of study drug
Hypoglycemia Rescue: Alternate Glucose Response Definition	Number of subjects with either an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL or an increase in from baseline in plasma glucose concentration of at least 20 mg/dL within 30 minutes after administration of glucagon	At 30 minutes following administration of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glucose Area Under the Curve (AUC)	Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon	At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon
Plasma Glucose Maximum Concentration (Cmax)	Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Plasma Glucose Time to Maximum Concentration (Tmax)	Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Plasma Glucose Time to Concentration > 70 mg/dL	Pharmacodynamic endpoint of time to achieve a plasma glucose concentration > 70 mg/dL following administration of glucagon	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Time to Resolution of Hypoglycemia Symptoms	Time to resolution of mean autonomic, mean neuroglycopenic and mean total hypoglycemia symptom scores from baseline through 90 minutes following administration of glucagon.	At 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 and 90 minutes following administration of glucagon
Global Assessment of Hypoglycemia	Time to resolution of the overall sensation of hypoglycemia following administration of glucagon	At 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 and 90 minutes following administration of glucagon

Collaborators and Investigators

• Sponsor: Xeris Pharmaceuticals

Publications and helpful links

General Publications

• Christiansen MP, Cummins M, Prestrelski S, Close NC, Nguyen A, Junaidi K. Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for the symptomatic relief of severe hypoglycemia: two randomized crossover non-inferiority studies. BMJ Open Diabetes Res Care. 2021 Oct;9(1):e002137. doi: 10.1136/bmjdrc-2021-002137.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Actual): August 14, 2017
• Study Completion (Actual): September 25, 2017

Study Registration Dates

• First Submitted: January 12, 2016
• First Submitted That Met QC Criteria: January 12, 2016
• First Posted (Estimate): January 14, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2018
• Last Update Submitted That Met QC Criteria: September 29, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: XSGP-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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