Glucagon Infusion in T1D Patients With Recurrent Severe Hypoglycemia: Effects on Counter-Regulatory Responses

NCT03490942 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: XSGO-AF01
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 5

Brief Summary

This is a prospective, randomized, controlled, double-blind, parallel 4-group trial with the primary analysis after 4 weeks of treatment with continuous subcutaneous glucagon infusion (CSGI) or placebo. After a 1-week qualification on continuous glucose monitoring (CGM), subjects will have their baseline hypoglycemia counter-regulatory response hormones quantified using a step-wise hypoglycemia induction procedure. Subjects meeting eligibility requirements will be randomized to 1 of 4 treatment groups, 2 glucagon, 2 placebo. Subjects will receive blinded study drug for 4 weeks, and they will be followed for an additional 26 weeks post-treatment. Subjects' counter-regulatory hormone response will be measured at baseline, the end of treatment (4 weeks), and 13 and 26 weeks after treatment ends.

Conditions

Hypoglycemia Unawareness; Diabetes Mellitus, Type 1

Keywords

glucagon; hypoglycemia counter-regulation

Outcome Measures

Primary Outcomes (1)

• Plasma Epinephrine

  Plasma epinephrine concentration after 30 minutes of induced hypoglycemia. Change from baseline to the end of treatment will be assessed.

  0-30 minutes

Study Arms (4)

CSGI high infusion rate

EXPERIMENTAL

Glucagon given as a continuous subcutaneous infusion for 28 days

Drug: Glucagon

CSGI low infusion rate

EXPERIMENTAL

Glucagon given as a continuous subcutaneous infusion for 28 days

Drug: Glucagon

Placebo high infusion rate

PLACEBO COMPARATOR

Placebo given as a continuous subcutaneous infusion for 28 days

Drug: Placebo

Placebo low infusion rate

PLACEBO COMPARATOR

Placebo given as a continuous subcutaneous infusion for 28 days

Drug: Placebo

Interventions

Glucagon DRUG

CSI-Glucagon is a room temperature stable, non-aqueous, liquid formulation of glucagon.

Also known as: CSI-Glucagon, CGSI

CSGI high infusion rate; CSGI low infusion rate

Placebo DRUG

The placebo solution is a non-active formulation containing excipients only.

Placebo high infusion rate; Placebo low infusion rate

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females diagnosed with type 1 diabetes mellitus for at least 24 months.
• Random serum C-peptide concentration \< 0.5 ng/ml at Screening.
• Current use of multiple daily dosing insulin treatment \< 1 U/(kg\*day) total daily dose either administered with subcutaneous injections or continuous subcutaneous insulin infusion (CSII).
• Recurrent severe hypoglycemia as defined by minimally two events during the last year and at least one the last six months requiring not merely receiving third party intervention and either confirmation with a measured glucose \< 50 mg/dl, or prompt recovery from impaired consciousness. Events must be documented in patient chart prior to study entry. Events induced as a part of clinical diagnostics or experimentation do not qualify.
• Performs monitoring of glucose minimally 3 times a day. Patients using continuous glucose monitoring for monitoring should continue to do so during the course of the study.
• Age 21-64 years, inclusive, at screening.
• Willingness to provide informed consent and follow all study procedures, including using the Medtronic smart phone application "iPRO2mylog" for diabetes data logging and attending all scheduled visits.

You may not qualify if:

• Subjects using CSII, who do not use a Medtronic pump.
• Hemoglobin A1c ≥9.0% at Screening.
• Chronic kidney disease stage 4 or 5.
• Hepatic disease, including serum alanine transaminase (ALT) or aspartate transaminase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin \< 3.0 g/dL; or serum bilirubin \> 2.0.
• Hematocrit of less than or equal to 30% at Screening.
• Blood pressure (BP) reading at Screening where systolic BP \<90 or \>150 mm Hg, or diastolic BP \<50 or \>100 mm Hg.
• Clinically significant echocardiogram (ECG) abnormalities at Screening.
• Congestive heart failure, New York Heart Association (NYHA) class II, III or IV,
• History of myocardial infarction, unstable angina or revascularization within the past 6 months.
• History of a cerebrovascular accident.
• Current seizure disorder.
• History of pheochromocytoma or disorder with increased risk of pheochromocytoma (multiple endocrine neoplasia type 2, neurofibromatosis, or Von Hippel-Lindau disease).
• History of insulinoma.
• Major surgical operation within 30 days prior to Screening.
• Current bleeding disorder, treatment with warfarin, or platelet count below 50,000 at Screening.

Sponsors & Collaborators

• Xeris Pharmaceuticals: lead
• Integrated Medical Development: collaborator

Study Sites (5)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California, San Diego

San Diego, California, 92037, United States

Location

Emory University - Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Glucagon

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: B J. Witkin
• Organization: Xeris Pharmaceuticals

bwitkin@xerispharma.com

919-412-6483

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind, placebo-controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a prospective, randomized, controlled, double-blind, parallel 4-group trial with the primary analysis after 4 weeks treatment with CSGI or placebo.

Study Record Dates

• First Submitted: March 25, 2018
• First Posted: April 6, 2018
• Study Start: March 15, 2018
• Primary Completion: November 4, 2019
• Study Completion: February 10, 2020
• Last Updated: February 21, 2021
• Results First Posted: February 21, 2021

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)