NCT01994746

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
77

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 2013

Shorter than P25 for phase_3

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2013

Completed
19 days until next milestone

First Submitted

Initial submission to the registry

November 20, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

November 26, 2013

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

October 10, 2016

Completed
Last Updated

September 23, 2019

Status Verified

September 1, 2019

Enrollment Period

1.2 years

First QC Date

November 20, 2013

Results QC Date

May 26, 2016

Last Update Submit

September 5, 2019

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (1)

  • Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir

    Increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level defines treatment success. Due to the residual activity of circulating insulin, glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes following glucagon administration.

    Within 30 minutes after receiving glucagon at both dosing visits (glucose was measured at pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration)

Secondary Outcomes (9)

  • Nasal and Non-nasal Effects/Symptoms

    Pre-dose; 15, 30, 60, and 90 post glucagon administration

  • Recovery From Symptoms of Hypoglycemia

    Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon

  • Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir

    Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration

  • Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon

    Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

  • Maximum Change From Baseline Concentration (Cmax) of Glucagon

    Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

  • +4 more secondary outcomes

Study Arms (2)

Nasal Glucagon

EXPERIMENTAL

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.

Drug: Nasal Glucagon

Intramuscular Glucagon

ACTIVE COMPARATOR

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

Drug: Intramuscular Glucagon

Interventions

Nasal GlucagonDRUG
Also known as: AMG504-1, LY900018
Nasal Glucagon
Intramuscular GlucagonDRUG
Also known as: GlucaGen HypoKit
Intramuscular Glucagon

Eligibility Criteria

Age18 Years - 64 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Barbara Davis Center for Diabetes

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

University of Florida

Gainesville, Florida, 32605, United States

Location

Riley Hospital for Children Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55454, United States

Location

UPA Buffalo

Buffalo, New York, 14222, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

  • 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.

    PMID: 26681725BACKGROUND

  • 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.

    PMID: 38444629DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company
800-545-5979

Study Officials

  • 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)

    Eli Lilly and Company

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 20, 2013

First Posted

November 26, 2013

Study Start

November 1, 2013

Primary Completion

January 1, 2015

Study Completion

January 1, 2015

Last Updated

September 23, 2019

Results First Posted

October 10, 2016

Record last verified: 2019-09

Data Sharing

IPD Sharing
Will share

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
More information

Locations

US(8)