treatment of severe hypoglycemia MedDRA version: 20.1 Level: LLT Classification code 10021005 Term: Hypoglycemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: Xeris G-Pen
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: GLUCAGON
CAS Number: 16941-32-5
Sponsors
Xeris Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females diagnosed with T1D for at least 24 months. Women of childbearing potential require a negative urine pregnancy test and must use medically accepted contraception throughout the study and for 7 days after the last dose of study drug. Nursing mothers will be allowed to participate in the study. However, breast feeding during the inpatient study visits (Visits 2 and 3) and for 48 hours after each dose of study drug is not allowed. 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 =65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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 Stage 2 or greater kidney failure. 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 150 mm Hg, and diastolic blood pressure (DBP) 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 II, III or IV. 13. History of myocardial infarction, unstable angina, or revascularization within the past 6 months. 14. History of a cerebrovascular accident 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. History of or 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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate that G-Pen 1 mg (test) is not inferior to GlucaGen Hypokit 1 mg (reference), in Type 1 diabetic (T1D) subjects in a state of insulin-induced hypoglycemia. ;Secondary Objective: The secondary objective of this study is to evaluate the safety and tolerability of G-Pen 1 mg versus GlucaGen Hypokit 1 mg in the study population.;Timepoint(s) of evaluation of this end point: during the trial;Primary end point(s): For the primary endpoint, groups will be compared for rates of achieving a positive plasma glucose response, defined as either a plasma glucose concentration > 70 mg/dL (> 3.88 mmol/L) or an increase in plasma glucose concentration > 20 mg/dL (> 1.11 mmol/L) within 30 minutes of study drug injection. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Rate of achieving a plasma glucose concentration > 70 mg/dL (> 3.88 mmol/L) within 30 minutes from injection of study drug. 2. Rate of achieving an increase in plasma glucose concentration > 20 mg/dL (>1.11 mmol/L) within 30 minutes from injection of study drug. 3. Rates of positive symptomatic response, defined as relief of neuroglycopenic symptoms within 30 minutes from a decision to dose. 4. Rates of positive treatment response, defined as exhibiting either a positive plasma glucose response or a positive symptomatic response. 5. Time to a positive plasma glucose response from injection of study drug. 6. Time to administer study drug from a decision to dose. 7. Pharmacodynamic (PD) characteristics of mean plasma glucose concentration (0 to 90 minutes post-dose), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), area under the concentration versus time curve from time 0 to 90 minutes (AUC(0-90)), and area under the concentration versus time curve from time 0 to 180 minutes (AUC(0-180)). 8. Time to (a) initial relief and (b) complete resolution of autonomic and neuroglycopenic symptoms of hypoglycemia from a decision to dose. 9. Time to resolution of the overall feeling of hypoglycemia from a decision to dose. 10. Safety endpoints, including: adverse event (AE)/serious adverse event (SAE) rates, and changes in vital signs, laboratory variables, and physical exam/electrocardiogram (ECG) findings. 11. Tolerability endpoints, including: Draize scale scores for injection site erythema and edema as assessed by the investigator, and injection site discomfort and duration as assessed by subject questionnaire responses. ;Timepoint(s) of evaluation of this end point: during the trial | — |
Countries
Austria, Germany, United States
Contacts
Public ContactDebby A. Powers
Xeris Pharmaceuticals, Inc
Outcome results
None listed