Glucose Response of G-Pen (Glucagon Injection) in Pediatric T1D Patients

• ClinicalTrials.gov Identifier: NCT03091673
• Recruitment Status: Completed
• First Posted: March 27, 2017
• Results First Posted: November 16, 2018
• Last Update Posted: December 11, 2018
• Sponsor: Xeris Pharmaceuticals
• Collaborator: The Emmes Company, LLC
• Information provided by (Responsible Party): Xeris Pharmaceuticals

Study Description

Brief Summary:

This is a sequential efficacy and safety study in pediatric patients with type 1 diabetes. Subjects will be administered insulin to induce a low normal glycemic state and will then receive an age-appropriate dose of G-Pen (glucagon injection) in a clinical research center (CRC) or comparable setting.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 1	Drug: Glucagon	Phase 3

Detailed Description:

This is an open-label, Phase 3 sequential efficacy and safety study in pediatric patients ages 2-17 with type 1 diabetes. Patients will complete the screening procedures up to 30 days before dosing to determine eligibility before enrollment to the treatment phase.

The procedure to evaluate the efficacy of G-Pen (glucagon injection) consists of inducing a low normal glycemic state by administration of insulin. Subjects ages 2-11 will then be given a 0.5 mg dose of G-Pen, while subjects ages 12-17 will receive a 1 mg dose of G-Pen. Subjects ages 12-17 will return for a second visit 1-4 weeks later and will receive a 0.5 mg dose of G-Pen when in a low normal glycemic stare. Plasma glucose and glucagon levels will be monitored for 90 and 180 minutes post-dosing, respectively, at all visits.

A follow-up phone call as a safety check will be conducted 3 - 14 days following administration of the final dose.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study to Evaluate the Glucose Response of G-Pen (Glucagon Injection) in Pediatric Patients With Type 1 Diabetes
• Actual Study Start Date: March 27, 2017
• Actual Primary Completion Date: September 7, 2017
• Actual Study Completion Date: September 27, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: G-Pen (glucagon injection) 0.5 mg; A single 0.5 mg subcutaneous (SC) injection of G-Pen (glucagon injection)	Drug: Glucagon; 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector; Other Name: G-Pen (glucagon injection)
Experimental: G-Pen (glucagon injection) 1.0 mg; A single 1.0 mg subcutaneous (SC) injection of G-Pen (glucagon injection)	Drug: Glucagon; 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector; Other Name: G-Pen (glucagon injection)

Outcome Measures

Primary Outcome Measures :

1. Change in Plasma Glucose [ Time Frame: 0-30 minutes ]
   The primary endpoint for this study is an evaluation of change in plasma glucose following treatment with G-Pen, with an emphasis on the increase from baseline to 30 minutes post-dosing.

Secondary Outcome Measures :

1. Time for Plasma Glucose to Increase by ≥25 mg/dL [ Time Frame: 0-90 minutes ]
   Time for plasma glucose to increase by ≥25 mg/dL from baseline will be analyzed descriptively for each age cohort.
2. Plasma Glucagon Area Under the Curve [ Time Frame: 0-90 minutes ]
   Plasma glucagon area under the curve (AUC) for each age cohort will be analyzed descriptively.
3. Plasma Glucagon Cmax [ Time Frame: 0-180 minutes ]
   Plasma glucagon maximum concentration for each age cohort will be analyzed descriptively.
4. Plasma Glucagon Tmax [ Time Frame: 0-180 minutes ]
   Plasma glucagon time to maximum concentration for each age cohort will be analyzed descriptively.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• diagnosed with T1D for at least 6 months at Screening.
• current usage of daily insulin treatment.

Exclusion Criteria:

• pregnant or nursing
• 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 venous access
• current seizure disorder
• history of pheochromocytoma or disorder with increased risk of pheochromocytoma
• history of insulinoma
• history of glycogen storage disease.
• active use of alcohol or drugs of abuse
• administration of glucagon within 14 days of the first treatment visit
• participation in other studies involving an investigational drug or device within 30 days

Contacts and Locations

Locations

United States, California

Stanford University

Stanford, California, United States, 94305

United States, Colorado

Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, United States, 80045

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06511

United States, Florida

University of Florida

Gainesville, Florida, United States, 32611

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52422

United States, New York

Women & Children's Hospital of Buffalo

Buffalo, New York, United States, 14222

Sponsors and Collaborators

Xeris Pharmaceuticals

The Emmes Company, LLC

  Study Documents (Full-Text)

Documents provided by Xeris Pharmaceuticals:

Study Protocol  [PDF] December 6, 2016

Statistical Analysis Plan  [PDF] August 16, 2017

More Information

• Responsible Party: Xeris Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03091673
• Other Study ID Numbers: XSGP-302
• First Posted: March 27, 2017
• Results First Posted: November 16, 2018
• Last Update Posted: December 11, 2018
• Last Verified: November 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:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; 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