Phase 3
N=132
G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes
Insulin Hypoglycemia · Type 1 Diabetes Mellitus · Severe Hypoglycemia
Bottom Line
View on ClinicalTrials.gov: NCT03738865 ↗Enrolled (actual)
132
Serious AEs
0.0%
Results posted
May 2020
Primary outcome: Primary: Severe Hypoglycemia Rescue — 127; 123 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- G-Pen (Drug); Novo Glucagon (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Xeris Pharmaceuticals
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Severe Hypoglycemia Rescue |
127; 123 | — |
| SECONDARY Plasma Glucose Response 1 |
127; 123 | — |
| SECONDARY Plasma Glucose Response 2 |
127; 123 | — |
| SECONDARY Administration Time |
0.79; 1.76 | — |
| SECONDARY Hypoglycemia Resolution |
15.69; 15.32 | — |
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 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.
Eligibility Criteria
Inclusion Criteria
- Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months.
- Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
- Age 18 to 75 years, inclusive.
- Random serum C-peptide concentration 10% at Screening.
- Body mass index (BMI) > 40 kg/m2.
- Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy.
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or greater than 3 times the upper limit of normal.
- Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL.
- Hematocrit 150 mm Hg, and diastolic blood pressure (DBP) 100 mm Hg.
- Clinically significant electrocardiogram (ECG) abnormalities.
- Use of total insulin dose per day > 2 U/kg.
- Inadequate venous access.
- Congestive heart failure, New York Heart Association (NYHA) class III or IV.
- History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
- History of a cerebrovascular accident in the past 6 months or with major neurological deficits.
- 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.
- Major surgical operation within 30 days prior to Screening.
- Current seizure disorder (other than with suspect or documented hypoglycemia).
- Current bleeding disorder, treatment with warfarin, or platelet count below 50 × 109 per liter.
- History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis, or Von Hippel-Lindau disease).
- History of insulinoma.
- 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.
- History of glycogen storage disease.
- 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.
- 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).
- Administration of glucagon within 7 days of Screening.
- 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.
- Any other reason the Investigator deems exclusionary.
Data sourced from ClinicalTrials.gov (NCT03738865). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.