Phase 3
N=81
G-Pen™ Compared to Lilly Glucagon for Hypoglycemia Rescue in Adults With Type 1 Diabetes
Insulin Hypoglycemia · Type 1 Diabetes Mellitus · Severe Hypoglycemia
Bottom Line
View on ClinicalTrials.gov: NCT03439072 ↗Enrolled (actual)
81
Serious AEs
0.0%
Results posted
May 2019
Primary outcome: Primary: Number of Subjects With a Positive Glucose Response — 76; 78 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- G-Pen (Drug); Lilly Glucagon (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Xeris Pharmaceuticals
- Primary completion
- Apr 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects With a Positive Glucose Response |
76; 78 | — |
| SECONDARY Time for Positive Glucose Response |
12.17; 8.58 | — |
| SECONDARY Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Positive Glucose Increase |
76; 78 | — |
| SECONDARY Number of Subjects With a Positive Glucose Increase |
76; 78 | — |
| SECONDARY Time for Positive Glucose Increase |
11.36; 8.02 | — |
| SECONDARY Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Relief of Neuroglycopenic Symptoms |
76; 78 | — |
| SECONDARY Number of Subjects With Relief of Neuroglycopenic Symptoms |
74; 77 | — |
| SECONDARY Time to Resolution of Autonomic Symptoms |
13.8; 12.0 | — |
| SECONDARY Time to Resolution of Neuroglycopenic Symptoms |
14.2; 12.2 | — |
| SECONDARY Time to Resolution of the Feeling of Hypoglycemia |
11.6; 13.1 | — |
| SECONDARY Glucose AUC |
33686.04; 33538.60 | — |
| SECONDARY Glucose Cmax |
238.32; 228.11 | — |
| SECONDARY Glucose Tmax |
125.67; 113.89 | — |
| SECONDARY Glucagon Preparation and Administration Time |
27.3; 97.2 | — |
Summary
This is a non-inferiority, 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 Lilly 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 hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose 70.0 mg/dL 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 procedure 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 females diagnosed with type 1 diabetes mellitus for at least 24 months.
- Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
- Age 18-75 years, inclusive.
- Random serum C-peptide concentration 9.0% at Screening.
- BMI > 40 kg/m2.
- Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease. requiring renal replacement therapy.
- Serum ALT or 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 of less than or equal to 30%.
- BP readings at Screening where SBP 150 mm Hg, and DBP 100 mm Hg.
- Clinically significant ECG abnormalities.
- Use of > 2.0 U/kg total insulin dose per day.
- Inadequate venous access.
- Congestive heart failure, NYHA class III or IV.
- History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
- History of a cerebrovascular accident in past 6 months or with major neurological deficits.
- Active malignancy within 5 years from Screening, except basal cell or squamous cell skin cancers. 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 x 10e9 per liter.
- History of pheochromocytoma or disorder with increased risk of pheochromocytoma (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 & trehalose) in the investigational formulation.
- History of glycogen storage disease.
- Subject tests positive for HIV, HCV or HBV infection (HBsAg+) at Screening.
- Active substance or alcohol abuse (more than 21 drinks/wk. for males or 14 drinks/wk. for females). Subjects reporting active marijuana use or testing positive for tetrahydrocannabinol (THC) via rapid urine test will be allowed to participate in the study at the discretion of the Investigator.
- Administration of glucagon within 28 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 reason the Investigator deems exclusionary.
Data sourced from ClinicalTrials.gov (NCT03439072). 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.