G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes

G-Pen (Glucagon Injection) Compared to GlucaGen® Hypokit® (Glucagon) for Induced Hypoglycemia Rescue in Adults With T1D: A Phase 3 Multi-center, Randomized, Controlled, Single Blind, 2-way Crossover Study to Evaluate Efficacy and Safety

This is a multi-center, randomized, controlled, single-blind, two-way crossover efficacy and safety study in subjects with Type 1 diabetes mellitus. The study involves two daytime clinical research center (CRC) visits with random assignment to receive G-Pen glucagon 1 mg during one period and Novo Glucagon 1 mg during the other. Each daytime visit is preceded by an overnight stay in the CRC. In the morning of the inpatient study visit, the subject is brought into a state of severe hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose < 54 mg/dL (3 mmol/L) is verified, the subject is administered a dose of G-Pen or Novo Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of >70.0 mg/dL (3.89 mmol/L) or an increase of > 20 mg/dL (>1.11 mmol/L) within 30 minutes of glucagon administration indicating a positive response. After 3 hours, the subject is given a meal and discharged when medically stable. After a wash-out period of 7 to 28 days, subjects return to the CRC, and the procedures are repeated with each subject crossed over to the other treatment. A follow-up visit as a safety check is conducted 2-7 days following administration of the final dose of study drug.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus; Severe Hypoglycemia; Insulin Hypoglycemia
• Intervention / Treatment: Drug: G-Pen; Drug: Novo Glucagon

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Medizinische Universität Graz-Center for Medical Research
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Diabetes & Endocrinology
  • Quebec
    • Montréal, Quebec, Canada, H3P 3P1
      • Altasciences
• United States
  • California
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • PPD-Las Vegas Clinical Research Unit
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Research Center

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:

1. Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months.
2. Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
3. Age 18 to 75 years, inclusive.
4. Random serum C-peptide concentration < 0.6 ng/mL.
5. Willingness to follow all study procedures, including attending all clinic visits.
6. Subject has provided informed consent as evidenced by a signed and dated informed consent form (ICF) completed before any trial-related activities occur.

Exclusion Criteria:

1. Pregnancy
2. Glycated hemoglobin (HbA1c) > 10% at Screening.
3. Body mass index (BMI) > 40 kg/m2.
4. Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy.
5. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or greater than 3 times the upper limit of normal.
6. Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL.
7. Hematocrit < 30%.
8. Blood pressure (BP) readings at Screening where systolic blood pressure (SBP) < 90 or > 150 mm Hg, and diastolic blood pressure (DBP) < 50 or > 100 mm Hg.
9. Clinically significant electrocardiogram (ECG) abnormalities.
10. Use of total insulin dose per day > 2 U/kg.
11. Inadequate venous access.
12. Congestive heart failure, New York Heart Association (NYHA) class III or IV.
13. History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
14. History of a cerebrovascular accident in the past 6 months or with major neurological deficits.
15. Active malignancy within 5 years from Screening, except basal cell or squamous cell skin cancers. Any history of breast cancer or malignant melanoma will be exclusionary.
16. Major surgical operation within 30 days prior to Screening.
17. Current seizure disorder (other than with suspect or documented hypoglycemia).
18. Current bleeding disorder, treatment with warfarin, or platelet count below 50 × 109 per liter.
19. History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis, or Von Hippel-Lindau disease).
20. History of insulinoma.
21. History of allergies to glucagon or glucagon-like products, or any history of significant hypersensitivity to glucagon or any related products or to any of the excipients (DMSO and trehalose) in the investigational formulation.
22. History of glycogen storage disease.
23. Subject tests positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection (hepatitis B surface antigen positive [HBsAg+]) at Screening.
24. Active substance other than tetrahydrocannabinol (THC) or alcohol abuse (more than 21 drinks per week for male subjects or 14 drinks per week for female subject).
25. Administration of glucagon within 7 days of Screening.
26. Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before Screening for the current study and during participation in the current study.
27. Any other reason the Investigator deems exclusionary.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: G-Pen followed by Novo Glucagon; 1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit	Drug: G-Pen; 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector; Other Names: glucagon; Drug: Novo Glucagon; 1 mg subcutaneous injection of Novo Glucagon (glucagon injection); Other Names: Glucagen Hypokit
ACTIVE_COMPARATOR: Novo Glucagon followed by G-Pen; 1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit	Drug: G-Pen; 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector; Other Names: glucagon; Drug: Novo Glucagon; 1 mg subcutaneous injection of Novo Glucagon (glucagon injection); Other Names: Glucagen Hypokit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe Hypoglycemia Rescue	Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration > 20 mg/dL (> 1.11 mmol/L) 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 Response 1	Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) within 30 minutes of a decision to dose	At 30 minutes following a decision to administer study drug
Plasma Glucose Response 2	Number of subjects with an increase in plasma glucose concentration > 20 mg/dL (> 1.11 mmol/L) after administration of glucagon.	At 0-30 minutes following a decision to administer study drug
Administration Time	Mean time (minutes) to administer study drug from a decision to dose	At 0-10 minutes from a decision to administer study drug
Hypoglycemia Resolution	Mean time (minutes) to complete resolution of the overall sensation of hypoglycemia from a decision to dose	At 0-90 minutes following administration of study drug

Collaborators and Investigators

• Sponsor: Xeris Pharmaceuticals
• Collaborators: Empiristat, Inc.

Publications and helpful links

General Publications

• Pieber TR, Aronson R, Christiansen MP, Bode B, Junaidi K, Conoscenti V. Efficacy, safety, tolerability, and noninferiority phase 3 study of glucagon as a ready-to-use room temperature liquid stable formulation versus a lyophilised formulation for the biochemical recovery and symptomatic relief of insulin-induced severe hypoglycaemia in adults with type 1 diabetes. Diabetes Obes Metab. 2022 Jul;24(7):1394-1397. doi: 10.1111/dom.14699. Epub 2022 Apr 28. No abstract available.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 27, 2018
• Primary Completion (ACTUAL): March 29, 2019
• Study Completion (ACTUAL): April 2, 2019

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: November 8, 2018
• First Posted (ACTUAL): November 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 22, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: hypoglycemia; glucagon
• 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-304

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