Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults

NCT ID: NCT01994746

Last Updated: 2019-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2015-01-31

Brief Summary

The purpose of this study is to assess the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of 3 milligrams (mg) glucagon (glucagon nasal powder) administered nasally compared with commercially available glucagon given by intramuscular injection.

Detailed Description

Each glucagon dosing visit was conducted after an overnight fast of at least 8 h with a starting plasma glucose >= 90 mg/dL. Hypoglycemia was induced by an intravenous (IV) infusion of regular insulin diluted in normal saline during the clinic visit. Five minutes after stopping the insulin infusion (once the plasma glucose was <60 mg/dL), participants were treated with either a 3 mg glucagon dose nasally or 1 mg of glucagon administered by intramuscular (IM) injection.

After a wash-out period of 7 days or more, participants returned to the clinic and the procedure repeated with each participant crossed over to the other treatment. As such, each participant underwent two episodes of insulin-induced hypoglycemia in random order and received glucagon nasal powder during one episode and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other episode.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nasal Glucagon

At one visit, a glucagon dose of 3 mg was administered in a nostril with a prefilled delivery device that delivers a single dose upon activation.

Group Type: EXPERIMENTAL

Nasal Glucagon

Intervention Type: DRUG

Intramuscular Glucagon

At a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular \[IM\]).

Group Type: ACTIVE_COMPARATOR

Intramuscular Glucagon

Intervention Type: DRUG

Interventions

Nasal Glucagon

Intervention Type: DRUG

Intramuscular Glucagon

Intervention Type: DRUG

Other Intervention Names

AMG504-1; LY900018; GlucaGen HypoKit

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of either type 1 diabetes receiving daily insulin since the time of diagnosis for at least 2 years or type 2 diabetes receiving multiple daily insulin doses for at least 2 years
• At least 18.0 years of age and less than 65.0 years
• Body mass index (BMI) greater than or equal to 20.0 and below or equal to 35.0 kilograms per meter squared (kg/m²)
• Weighs at least 50 kg (110 pounds)
• Females must meet one of the following criteria:

• Of childbearing potential but agree to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from the screening until study completion)
• Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
• In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the Investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations
• Willingness to adhere to the study requirements

Exclusion Criteria

• Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are lactating
• History of hypersensitivity to glucagon or any related products or severe hypersensitivity reactions (such as angioedema) to any drugs
• Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the investigator could interfere with the absorption, distribution, metabolism or excretion of drugs or could potentiate or predispose to undesired effects
• History of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma.
• History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the 1 month prior to enrolling in the study
• Use of daily systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs
• History of epilepsy or seizure disorder
• Regularly consumes 3 or more alcoholic beverages per day
• Use of an Investigational Product in another clinical trial within the past 30 days
• Donated 225 milliliters (mL) or more of blood in the previous 8 weeks before the first glucagon dosing

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

T1D Exchange Clinic Network Coordinating Center

UNKNOWN

Sponsor Role: collaborator

Locemia Solutions ULC

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Barbara Davis Center for Diabetes

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

University of Florida

Gainesville, Florida, United States

Riley Hospital for Children Indiana University Health

Indianapolis, Indiana, United States

University of Minnesota

Minneapolis, Minnesota, United States

UPA Buffalo

Buffalo, New York, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Rickels MR, Ruedy KJ, Foster NC, Piche CA, Dulude H, Sherr JL, Tamborlane WV, Bethin KE, DiMeglio LA, Wadwa RP, Ahmann AJ, Haller MJ, Nathan BM, Marcovina SM, Rampakakis E, Meng L, Beck RW; T1D Exchange Intranasal Glucagon Investigators. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care. 2016 Feb;39(2):264-70. doi: 10.2337/dc15-1498. Epub 2015 Dec 17.

Reference Type: BACKGROUND

PMID: 26681725 (View on PubMed)

Seaquist E, Gimenez M, Yan Y, Matsuhisa M, Kao CY, Wadwa RP, Nagai Y, Khunti K. Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials. J Endocr Soc. 2024 Feb 26;8(4):bvae034. doi: 10.1210/jendso/bvae034. eCollection 2024 Feb 19.

Reference Type: DERIVED

PMID: 38444629 (View on PubMed)

Other Identifiers

INGluc001

Identifier Type: OTHER

Identifier Source: secondary_id

I8R-MC-IGBC

Identifier Type: OTHER

Identifier Source: secondary_id

AMG106

Identifier Type: OTHER

Identifier Source: secondary_id

16422

Identifier Type: -

Identifier Source: org_study_id