Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02656069
Recruitment Status : Completed
First Posted : January 14, 2016
Results First Posted : September 28, 2018
Last Update Posted : October 30, 2018
Sponsor:
Information provided by (Responsible Party):
Xeris Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE January 12, 2016
First Posted Date  ICMJE January 14, 2016
Results First Submitted Date  ICMJE August 31, 2018
Results First Posted Date  ICMJE September 28, 2018
Last Update Posted Date October 30, 2018
Actual Study Start Date  ICMJE March 15, 2017
Actual Primary Completion Date August 14, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2018)
  • Hypoglycemia Rescue: Intent-to-Treat Population [ Time Frame: 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: Per Protocol Population [ Time Frame: 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 [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: January 12, 2016)
Hypoglycemia rescue [ Time Frame: At 0, 5, 10, 15, 20, 25 and 30 minutes following administration of study drug ]
Treatment success will be based on a primary endpoint of an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2018)
  • Plasma Glucose Area Under the Curve (AUC) [ Time Frame: 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
  • Plasma Glucose Maximum Concentration (Cmax) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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
  • Time to Resolution of Hypoglycemia Symptoms [ 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 ]
    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 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 ]
    Time to resolution of the overall sensation of hypoglycemia following administration of glucagon
Original Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2016)
  • Plasma Glucose Area Under the Curve (AUC) [ Time Frame: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon ]
    Pharmacodynamic endpoint of plasma glucose AUC from baseline to 4 hours following administration of glucagon
  • Plasma Glucose Maximum Concentration (Cmax) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: At -5, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes following administration of glucagon ]
    Pharmacodynamic endpoint of time from baseline to achieve a plasma glucose concentration > 70 mg/dL following administration of glucagon
  • Hypoglycemia Symptoms [ Time Frame: At 0, 5, 10, 15, 20, 25 and 30 minutes following administration of glucagon ]
    Change in autonomic and neuroglycopenic symptoms from baseline through 30 minutes following administration of glucagon.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of G-Pen Compared to Lilly Glucagon for Hypoglycemia Rescue in Adult Type 1 Diabetics
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypoglycemia
  • Diabetes Mellitus, Type 1
Intervention  ICMJE
  • Drug: G-Pen (glucagon injection)
    1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector
    Other Name: glucagon
  • Drug: Lilly Glucagon (glucagon injection [rDNA origin])
    1 mg of Lilly glucagon reconstituted from lyophilized powder
    Other Name: glucagon
Study Arms  ICMJE
  • G-Pen first, then Lilly Glucagon
    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])
    Interventions:
    • Drug: G-Pen (glucagon injection)
    • Drug: Lilly Glucagon (glucagon injection [rDNA origin])
  • Lilly Glucagon first, then G-Pen
    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)
    Interventions:
    • Drug: G-Pen (glucagon injection)
    • Drug: Lilly Glucagon (glucagon injection [rDNA origin])
Publications * 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). pii: e002137. doi: 10.1136/bmjdrc-2021-002137.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 16, 2017)
80
Original Estimated Enrollment  ICMJE
 (submitted: January 12, 2016)
100
Actual Study Completion Date  ICMJE September 25, 2017
Actual Primary Completion Date August 14, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02656069
Other Study ID Numbers  ICMJE XSGP-301
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Xeris Pharmaceuticals
Study Sponsor  ICMJE Xeris Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Xeris Pharmaceuticals
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP