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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03738865
• Other study ID #: XSGP-304
• Status: Completed
• Phase: Phase 3
• Start date: September 27, 2018
• Est. completion date: April 2, 2019

Study information

• Verified date: May 2020
• Source: Xeris Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: April 2, 2019
• Est. primary completion date: March 29, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Hypoglycemia
• Insulin Hypoglycemia
• Severe Hypoglycemia
• Type 1 Diabetes Mellitus

Intervention

Drug:
• G-Pen
1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector
• Novo Glucagon
1 mg subcutaneous injection of Novo Glucagon (glucagon injection)

Locations

Country	Name	City	State
Austria	Medizinische Universität Graz-Center for Medical Research	Graz
Canada	AltaSciences	Montréal	Quebec
Canada	LMC Diabetes & Endocrinology	Toronto	Ontario
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	PPD-Las Vegas Clinical Research Unit	Las Vegas	Nevada
United States	Rainier Research Center	Renton	Washington
United States	Diablo Clinical Research	Walnut Creek	California

Sponsors (2)

Lead Sponsor	Collaborator
Xeris Pharmaceuticals	Empiristat, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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