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

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: August 14, 2017

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.

Interventions

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

Arms, Groups and Cohorts

  • Other: 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])
  • Other: 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)

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Xeris Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor

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