Clinical trial NCT02656069: Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypoglycemia
Diabetes Mellitus, Type 1
Lead sponsor: Xeris Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-01-14
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Hypoglycemia Rescue: Intent-to-Treat Population
timeFrame: At 30 minutes following administration of study drug
measure: Hypoglycemia Rescue: Per Protocol Population
timeFrame: At 30 minutes following administration of study drug
measure: Hypoglycemia Rescue: Alternate Glucose Response Definition
timeFrame: At 30 minutes following administration of study drug
Secondary outcomes:
measure: Plasma Glucose Area Under the Curve (AUC)
timeFrame: At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon
measure: Plasma Glucose Maximum Concentration (Cmax)
timeFrame: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
measure: Plasma Glucose Time to Maximum Concentration (Tmax)
timeFrame: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
measure: Plasma Glucose Time to Concentration > 70 mg/dL
timeFrame: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
measure: Time to Resolution of Hypoglycemia Symptoms
timeFrame: 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
measure: Global Assessment of Hypoglycemia
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chula Vista
country: United States
facility: ProSciento, Inc.
state: California
city: Escondido
country: United States
facility: AMCR Institute
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Renton
country: United States
facility: Rainier Research
state: Washington
city: Toronto
country: Canada
facility: LMC Diabetes & Endocrinology
state: Ontario
Study officials:
References:
citation: Christiansen MP, Cummins M, Prestrelski S, Close NC, Nguyen A, Junaidi K. Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for the symptomatic relief of severe hypoglycemia: two randomized crossover non-inferiority studies. BMJ Open Diabetes Res Care. 2021 Oct;9(1):e002137. doi: 10.1136/bmjdrc-2021-002137.