G-Pen Compared to Glucagen Hypokit for Severe Hypoglycemia Rescue in Adults With Type 1 Diabetes

NCT03738865 | Completed Phase 3 Results FDA Drug

• 1 other identifier: XSGP-304
• Study Type: interventional
• Target: 132
• Locations: 3 countries
• Sites: 7

Brief Summary

This is a multi-center, randomized, controlled, single-blind, two-way crossover efficacy and safety study in subjects with Type 1 diabetes mellitus. The study involves two daytime clinical research center (CRC) visits with random assignment to receive G-Pen glucagon 1 mg during one period and Novo Glucagon 1 mg during the other. Each daytime visit is preceded by an overnight stay in the CRC. In the morning of the inpatient study visit, the subject is brought into a state of severe hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose \< 54 mg/dL (3 mmol/L) is verified, the subject is administered a dose of G-Pen or Novo Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of \>70.0 mg/dL (3.89 mmol/L) or an increase of \> 20 mg/dL (\>1.11 mmol/L) within 30 minutes of glucagon administration indicating a positive response. After 3 hours, the subject is given a meal and discharged when medically stable. After a wash-out period of 7 to 28 days, subjects return to the CRC, and the procedures are repeated with each subject crossed over to the other treatment. A follow-up visit as a safety check is conducted 2-7 days following administration of the final dose of study drug.

Conditions

Insulin Hypoglycemia; Type 1 Diabetes Mellitus; Severe Hypoglycemia

Keywords

glucagon; hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Severe Hypoglycemia Rescue

  Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration \> 20 mg/dL (\> 1.11 mmol/L) within 30 minutes after administration of glucagon

  At 30 minutes following administration of study drug

Secondary Outcomes (4)

• Plasma Glucose Response 1

  At 30 minutes following a decision to administer study drug

• Plasma Glucose Response 2

  At 0-30 minutes following a decision to administer study drug

• Administration Time

  At 0-10 minutes from a decision to administer study drug

• Hypoglycemia Resolution

  At 0-90 minutes following administration of study drug

Study Arms (2)

G-Pen followed by Novo Glucagon

EXPERIMENTAL

1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit

Drug: G-Pen; Drug: Novo Glucagon

Novo Glucagon followed by G-Pen

ACTIVE COMPARATOR

1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit

Drug: G-Pen; Drug: Novo Glucagon

Interventions

G-Pen DRUG

1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector

Also known as: glucagon

G-Pen followed by Novo Glucagon; Novo Glucagon followed by G-Pen

Novo Glucagon DRUG

1 mg subcutaneous injection of Novo Glucagon (glucagon injection)

Also known as: Glucagen Hypokit

G-Pen followed by Novo Glucagon; Novo Glucagon followed by G-Pen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months.
• Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
• Age 18 to 75 years, inclusive.
• Random serum C-peptide concentration \< 0.6 ng/mL.
• Willingness to follow all study procedures, including attending all clinic visits.
• Subject has provided informed consent as evidenced by a signed and dated informed consent form (ICF) completed before any trial-related activities occur.

You may not qualify if:

• Pregnancy
• Glycated hemoglobin (HbA1c) \> 10% at Screening.
• Body mass index (BMI) \> 40 kg/m2.
• Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease requiring renal replacement therapy.
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or greater than 3 times the upper limit of normal.
• Hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL.
• Hematocrit \< 30%.
• Blood pressure (BP) readings at Screening where systolic blood pressure (SBP) \< 90 or \> 150 mm Hg, and diastolic blood pressure (DBP) \< 50 or \> 100 mm Hg.
• Clinically significant electrocardiogram (ECG) abnormalities.
• Use of total insulin dose per day \> 2 U/kg.
• Inadequate venous access.
• Congestive heart failure, New York Heart Association (NYHA) class III or IV.
• History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
• History of a cerebrovascular accident in the past 6 months or with major neurological deficits.
• Major surgical operation within 30 days prior to Screening.

Sponsors & Collaborators

• Xeris Pharmaceuticals: lead
• Empiristat, Inc.: collaborator

Study Sites (7)

Diablo Clinical Research

Walnut Creek, California, 94598, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

PPD-Las Vegas Clinical Research Unit

Las Vegas, Nevada, 89113, United States

Location

Rainier Research Center

Renton, Washington, 98057, United States

Location

Medizinische Universität Graz-Center for Medical Research

Graz, 8010, Austria

Location

LMC Diabetes & Endocrinology

Toronto, Ontario, M4G 3E8, Canada

Location

AltaSciences

Montreal, Quebec, H3P 3P1, Canada

Location

Related Publications (1)

• Pieber TR, Aronson R, Christiansen MP, Bode B, Junaidi K, Conoscenti V. Efficacy, safety, tolerability, and noninferiority phase 3 study of glucagon as a ready-to-use room temperature liquid stable formulation versus a lyophilised formulation for the biochemical recovery and symptomatic relief of insulin-induced severe hypoglycaemia in adults with type 1 diabetes. Diabetes Obes Metab. 2022 Jul;24(7):1394-1397. doi: 10.1111/dom.14699. Epub 2022 Apr 28. No abstract available.

  PMID: 35322535 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

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: Chelsea Boundy
• Organization: Xeris Pharmaceuticals, Inc.

cboundy@xerispharma.com

312-517-1466

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 13, 2018
• Study Start: September 27, 2018
• Primary Completion: March 29, 2019
• Study Completion: April 2, 2019
• Last Updated: May 22, 2020
• Results First Posted: May 13, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); US (4); CA (2)