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

• 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: Xeris Pharmaceuticals
• Information provided by (Responsible Party): Xeris Pharmaceuticals

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.

Condition or disease	Intervention/treatment	Phase
Hypoglycemia; Diabetes Mellitus, Type 1	Drug: G-Pen (glucagon injection); Drug: Lilly Glucagon (glucagon injection [rDNA origin])	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 15, 2017
• Actual Primary Completion Date: August 14, 2017
• Actual Study Completion Date: September 25, 2017

Arms and Interventions

Arm	Intervention/treatment
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])	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
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)	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

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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
3. 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 Outcome Measures :

1. 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
2. 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
3. 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
4. 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
5. 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.
6. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

ProSciento, Inc.

Chula Vista, California, United States, 91911

AMCR Institute

Escondido, California, United States, 92025

Diablo Clinical Research

Walnut Creek, California, United States, 94598

United States, Texas

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States, 78229

United States, Washington

Rainier Research

Renton, Washington, United States, 98057

Canada, Ontario

LMC Diabetes & Endocrinology

Toronto, Ontario, Canada, M4G 3E8

Sponsors and Collaborators

Xeris Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Xeris Pharmaceuticals:

Study Protocol and Statistical Analysis Plan  [PDF] March 16, 2017

More Information

• Responsible Party: Xeris Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02656069 History of Changes
• Other Study ID Numbers: XSGP-301
• First Posted: January 14, 2016
• Results First Posted: September 28, 2018
• Last Update Posted: October 30, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypoglycemia; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Glucagon; Glucagon-Like Peptide 1; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Incretins