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

Primary Purpose

Hypoglycemia, Diabetes Mellitus, Type 1

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
G-Pen (glucagon injection)
Lilly Glucagon (glucagon injection [rDNA origin])
Sponsored by
Xeris Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoglycemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • ProSciento, Inc.
  • AMCR Institute
  • Diablo Clinical Research
  • Clinical Trials of Texas, Inc.
  • Rainier Research
  • LMC Diabetes & Endocrinology

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

G-Pen first, then Lilly Glucagon

Lilly Glucagon first, then G-Pen

Arm Description

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])

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)

Outcomes

Primary Outcome Measures

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
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
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

Secondary Outcome Measures

Plasma Glucose Area Under the Curve (AUC)
Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon
Plasma Glucose Maximum Concentration (Cmax)
Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon
Plasma Glucose Time to Maximum Concentration (Tmax)
Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon
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
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.
Global Assessment of Hypoglycemia
Time to resolution of the overall sensation of hypoglycemia following administration of glucagon

Full Information

First Posted
January 12, 2016
Last Updated
September 29, 2018
Sponsor
Xeris Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02656069
Brief Title
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

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
March 15, 2017 (Actual)
Primary Completion Date
August 14, 2017 (Actual)
Study Completion Date
September 25, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xeris Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoglycemia, Diabetes Mellitus, Type 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
G-Pen first, then Lilly Glucagon
Arm Type
Other
Arm Description
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])
Arm Title
Lilly Glucagon first, then G-Pen
Arm Type
Other
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
G-Pen (glucagon injection)
Other Intervention Name(s)
glucagon
Intervention Description
1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector
Intervention Type
Drug
Intervention Name(s)
Lilly Glucagon (glucagon injection [rDNA origin])
Other Intervention Name(s)
glucagon
Intervention Description
1 mg of Lilly glucagon reconstituted from lyophilized powder
Primary Outcome Measure Information:
Title
Hypoglycemia Rescue: Intent-to-Treat Population
Description
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
Time Frame
At 30 minutes following administration of study drug
Title
Hypoglycemia Rescue: Per Protocol Population
Description
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
Time Frame
At 30 minutes following administration of study drug
Title
Hypoglycemia Rescue: Alternate Glucose Response Definition
Description
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
Time Frame
At 30 minutes following administration of study drug
Secondary Outcome Measure Information:
Title
Plasma Glucose Area Under the Curve (AUC)
Description
Pharmacodynamic endpoint of plasma glucose AUC from baseline to 90 minutes following administration of glucagon
Time Frame
At -5, 0, 10, 20, 30, 45, 60, and 90 minutes following administration of glucagon
Title
Plasma Glucose Maximum Concentration (Cmax)
Description
Pharmacodynamic endpoint of plasma glucose Cmax from baseline to 4 hours following administration of glucagon
Time Frame
At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Title
Plasma Glucose Time to Maximum Concentration (Tmax)
Description
Pharmacodynamic endpoint of plasma glucose Tmax from baseline to 4 hours following administration of glucagon
Time Frame
At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Title
Plasma Glucose Time to Concentration > 70 mg/dL
Description
Pharmacodynamic endpoint of time to achieve a plasma glucose concentration > 70 mg/dL following administration of glucagon
Time Frame
At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon
Title
Time to Resolution of Hypoglycemia Symptoms
Description
Time to resolution of mean autonomic, mean neuroglycopenic and mean total hypoglycemia symptom scores from baseline through 90 minutes following administration of glucagon.
Time Frame
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
Title
Global Assessment of Hypoglycemia
Description
Time to resolution of the overall sensation of hypoglycemia following administration of glucagon
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
ProSciento, Inc.
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
AMCR Institute
City
Escondido
State/Province
California
ZIP/Postal Code
92025
Country
United States
Facility Name
Diablo Clinical Research
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Clinical Trials of Texas, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Rainier Research
City
Renton
State/Province
Washington
ZIP/Postal Code
98057
Country
United States
Facility Name
LMC Diabetes & Endocrinology
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4G 3E8
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34620618
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.
Results Reference
derived

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

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