Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics

Phase 3

Completed

Conditions: Diabetes Mellitus, Type 1
Hypoglycemia

Interventions: Drug: G-Pen (glucagon injection)
Drug: Lilly Glucagon (glucagon injection [rDNA origin])

Registration Number: NCT02656069

Lead Sponsor: Xeris Pharmaceuticals

Brief Summary: This is a blinded, randomized crossover study to compare the safety and efficacy of G-Pen (glucagon injection) to Lilly Glucagon (glucagon for injection \[rDNA origin\]) for hypoglycemia rescue of adult patients with type 1 diabetes.

Detailed Description: This is a blinded, randomized, Phase 3 comparative efficacy and safety study in adults with type 1 diabetes. Patients will complete screening procedures up to 60 days before randomization to determine eligibility before enrollment to the treatment phase.

The procedure for evaluating the efficacy of the G-Pen (glucagon injection) consists of inducing hypoglycemia by intravenous administration of regular insulin diluted in normal saline. Each participant will undergo two episodes of insulin-induced hypoglycemia, and in random order will receive 1 mg G-Pen (glucagon injection) during one episode and 1 mg Lilly Glucagon during the other episode. There will be wash out period of 7-28 days between treatment visits.

Blood glucose levels will be monitored post-dosing, with a return of plasma glucose to a concentration \> 70 mg/dL within 30 minutes signifying successful hypoglycemia rescue. As a confirmation of efficacy, subjects will complete a questionnaire concerning changes in symptoms of hypoglycemia following treatment with glucagon.

Subjects will return for a follow-up safety visit 3-14 days following administration of the final dose of glucagon.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 80

Inclusion Criteria

diagnosed with type 1 diabetes mellitus for at least 24 months
usage of daily insulin treatment
random serum C-peptide concentration < 0.5 ng/mL

Exclusion Criteria

pregnant or nursing
HbA1c >9.0%
renal insufficiency
hepatic synthetic insufficiency
aspartate or alanine aminotransferase > 3 times the upper limit of normal
hematocrit less than or equal to 30%
use of > 2.0 U/kg total insulin dose per day
inadequate bilateral venous access in both arms
congestive heart failure, New York Heart Association class II, III or IV
active malignancy within 5 years, except basal cell or squamous cell skin cancers
history of breast cancer or malignant melanoma
major surgical operation within 30 days
current seizure disorder.
current bleeding disorder, treatment with warfarin, or platelet count below 50,000
history of pheochromocytoma or disorder with increased risk of pheochromocytoma
history of insulinoma
history of glycogen storage disease.
positive for HIV, hepatitis C virus or active hepatitis B virus infection
whole blood donation of 1 pint (500 mL) within 8 weeks
active substance or alcohol abuse
administration of glucagon within 28 days
participation in other studies involving an investigational drug or device within 30 days

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
G-Pen first, then Lilly Glucagon	Lilly Glucagon (glucagon injection [rDNA origin])	A single 1 mg subcutaneous (SC) injection of G-Pen (glucagon injection) with a 7-28 day wash-out, followed by a single 1 mg SC injection of Lilly Glucagon (glucagon injection \[rDNA origin\])
G-Pen first, then Lilly Glucagon	G-Pen (glucagon injection)	A single 1 mg subcutaneous (SC) injection of G-Pen (glucagon injection) with a 7-28 day wash-out, followed by a single 1 mg SC injection of Lilly Glucagon (glucagon injection \[rDNA origin\])
Lilly Glucagon first, then G-Pen	G-Pen (glucagon injection)	A single 1 mg SC injection of Lilly Glucagon (glucagon injection \[rDNA origin\]) with a 7-28 day wash-out, followed by a single 1 mg SC injection of G-Pen (glucagon injection)
Lilly Glucagon first, then G-Pen	Lilly Glucagon (glucagon injection [rDNA origin])	A single 1 mg SC injection of Lilly Glucagon (glucagon injection \[rDNA origin\]) with a 7-28 day wash-out, followed by a single 1 mg SC injection of G-Pen (glucagon injection)

Primary Outcome Measures

Name	Time	Method
Hypoglycemia Rescue: Per Protocol Population	At 30 minutes following administration of study drug	Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon
Hypoglycemia Rescue: Alternate Glucose Response Definition	At 30 minutes following administration of study drug	Number of subjects with either an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL or an increase in from baseline in plasma glucose concentration of at least 20 mg/dL within 30 minutes after administration of glucagon
Hypoglycemia Rescue: Intent-to-Treat Population	At 30 minutes following administration of study drug	Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon

Secondary Outcome Measures

Name	Time	Method
Plasma Glucose Area Under the Curve (AUC)	At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon	Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon
Time to Resolution of Hypoglycemia Symptoms	At 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 and 90 minutes following administration of glucagon	Time to resolution of mean autonomic, mean neuroglycopenic and mean total hypoglycemia symptom scores from baseline through 90 minutes following administration of glucagon.
Plasma Glucose Maximum Concentration (Cmax)	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon	Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon
Plasma Glucose Time to Maximum Concentration (Tmax)	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon	Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon
Plasma Glucose Time to Concentration > 70 mg/dL	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon	Pharmacodynamic endpoint of time to achieve a plasma glucose concentration \> 70 mg/dL following administration of glucagon
Global Assessment of Hypoglycemia	At 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 and 90 minutes following administration of glucagon	Time to resolution of the overall sensation of hypoglycemia following administration of glucagon

Trial Locations

Locations (7): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
ProSciento, Inc.
🇺🇸
Chula Vista, California, United States
AMCR Institute
🇺🇸
Escondido, California, United States
Diablo Clinical Research
🇺🇸
Walnut Creek, California, United States
Clinical Trials of Texas, Inc.
🇺🇸
San Antonio, Texas, United States
Rainier Research
🇺🇸
Renton, Washington, United States
LMC Diabetes & Endocrinology
🇨🇦
Toronto, Ontario, Canada