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

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

G-Pen (Glucagon Injection) Compared to Lilly Glucagon (Glucagon for Injection [RDNA Origin]) for Induced Hypoglycemia Rescue in Adult Patients With T1DM: A Phase 3, Multi-center, Randomized, Blinded, 2-Way Crossover Study to Evaluate Efficacy and Safety

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02656069
• Other study ID #: XSGP-301
• Status: Completed
• Phase: Phase 3
• Start date: March 15, 2017
• Est. completion date: September 25, 2017

Study information

• Verified date: September 2018
• Source: Xeris Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 25, 2017
• Est. primary completion date: August 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Drug:
• G-Pen (glucagon injection)
1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector
• Lilly Glucagon (glucagon injection [rDNA origin])
1 mg of Lilly glucagon reconstituted from lyophilized powder

Locations

Country	Name	City	State
Canada	LMC Diabetes & Endocrinology	Toronto	Ontario
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	ProSciento, Inc.	Chula Vista	California
United States	AMCR Institute	Escondido	California
United States	Rainier Research	Renton	Washington
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Diablo Clinical Research	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Xeris Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hypoglycemia Rescue: Intent-to-Treat Population	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	At 30 minutes following administration of study drug
Primary	Hypoglycemia Rescue: Per Protocol Population	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	At 30 minutes following administration of study drug
Primary	Hypoglycemia Rescue: Alternate Glucose Response Definition	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	At 30 minutes following administration of study drug
Secondary	Plasma Glucose Area Under the Curve (AUC)	Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon	At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon
Secondary	Plasma Glucose Maximum Concentration (Cmax)	Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Secondary	Plasma Glucose Time to Maximum Concentration (Tmax)	Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Secondary	Plasma Glucose Time to Concentration > 70 mg/dL	Pharmacodynamic endpoint of time to achieve a plasma glucose concentration > 70 mg/dL following administration of glucagon	At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Secondary	Time to Resolution of Hypoglycemia Symptoms	Time to resolution of mean autonomic, mean neuroglycopenic and mean total hypoglycemia symptom scores from baseline through 90 minutes following administration of glucagon.	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
Secondary	Global Assessment of Hypoglycemia	Time to resolution of the overall sensation of hypoglycemia following administration of glucagon	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