G-Pen™ Compared to Lilly Glucagon for Hypoglycemia Rescue in Adults With Type 1 Diabetes

NCT03439072 | Completed Phase 3 Results FDA Drug

• 1 other identifier: XSGP-303
• Study Type: interventional
• Target: 81
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a non-inferiority, 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 Lilly 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 hypoglycemia through IV administration of regular insulin diluted in normal saline. After a hypoglycemic state with plasma glucose \< 50 mg/dL is verified, the subject is administered a dose of G-Pen or Lilly Glucagon via subcutaneous injection. Plasma glucose levels are monitored for up to 180 minutes post-dosing, with a value of \>70.0 mg/dL 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 procedure 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)

• Number of Subjects With a Positive Glucose Response

  Increase in plasma glucose concentration from below 50.0 mg/dL to greater than 70.0 mg/dL within 30 minutes after receiving glucagon

  0 to 30 minutes post dose

Secondary Outcomes (13)

• Time for Positive Glucose Response

  0 to 180 minutes post dose

• Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Positive Glucose Increase

  0 to 30 minutes post dose

• Number of Subjects With a Positive Glucose Increase

  0 to 30 minutes post dose

• Time for Positive Glucose Increase

  0 to 180 minutes post dose

• Number of Subjects With a Positive Response for the Combination Endpoint: Positive Glucose Response/Relief of Neuroglycopenic Symptoms

  0 to 30 minutes post dose

Study Arms (2)

G-Pen followed by Lilly Glucagon

OTHER

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

Drug: G-Pen; Drug: Lilly Glucagon

Lilly Glucagon followed by G-Pen

OTHER

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

Drug: G-Pen; Drug: Lilly 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 Lilly Glucagon; Lilly Glucagon followed by G-Pen

Lilly Glucagon DRUG

1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\])

Also known as: GEK

G-Pen followed by Lilly Glucagon; Lilly 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 females diagnosed with type 1 diabetes mellitus for at least 24 months.
• Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia.
• Age 18-75 years, inclusive.
• Random serum C-peptide concentration \< 0.5 ng/mL.
• Willingness to follow all study procedures, including attending all clinic visits.
• Subject has provided informed consent as evidenced by a signed/dated informed consent form completed before any trial-related activities occur.

You may not qualify if:

• Pregnancy: For women of childbearing potential, there is a requirement for a negative urine pregnancy test and for agreement to use contraception throughout the study and for 7 days after the last dose of study glucagon. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
• Breastfeeding: Nursing mothers will be allowed into the study. However, breast feeding during the during inpatient study visits and for 48 hours after each dose of study drug is not allowed.
• HbA1c \>9.0% at Screening.
• BMI \> 40 kg/m2.
• Renal insufficiency (serum creatinine greater than 3.0 mg/dL) or end-stage renal disease. requiring renal replacement therapy.
• Serum ALT or 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 of less than or equal to 30%.
• BP readings at Screening where SBP \<90 or \>150 mm Hg, and DBP \<50 or \>100 mm Hg.
• Clinically significant ECG abnormalities.
• Use of \> 2.0 U/kg total insulin dose per day.
• Inadequate venous access.
• Congestive heart failure, NYHA class III or IV.
• History of myocardial infarction, unstable angina, or revascularization within the past 6 months.
• History of a cerebrovascular accident in past 6 months or with major neurological deficits.

Sponsors & Collaborators

• Xeris Pharmaceuticals: lead
• SGS S.A.: collaborator
• Integrated Medical Development: collaborator

Study Sites (6)

ProSciento, Inc.

Chula Vista, California, 91911, United States

Location

Diablo Clinical Research, Inc.

Walnut Creek, California, 94598, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

Rainier Clinical Research Center, Inc.

Renton, Washington, 98057, United States

Location

LMC ESD, Inc.

Toronto, Ontario, M4G 3E8, Canada

Location

Altasciences Algorithme Pharma

Montreal, Quebec, H3P 3P1, Canada

Location

Related Publications (1)

• Christiansen MP, Cummins M, Prestrelski S, Close NC, Nguyen A, Junaidi K. Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for the symptomatic relief of severe hypoglycemia: two randomized crossover non-inferiority studies. BMJ Open Diabetes Res Care. 2021 Oct;9(1):e002137. doi: 10.1136/bmjdrc-2021-002137.

  PMID: 34620618 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: Martin J. Cummins
• Organization: Xeris Pharmaceuticals, Inc.

mcummins@xerispharma.com

312-736-1624

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: February 13, 2018
• First Posted: February 20, 2018
• Study Start: January 23, 2018
• Primary Completion: April 18, 2018
• Study Completion: May 3, 2018
• Last Updated: February 17, 2020
• Results First Posted: May 30, 2019

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CA (2)