A Study of Glucagon Administered in Different Forms and Routes to Healthy Adults

A Single Site, Randomized, Four-Way, Four-Period PK/PD Crossover Phase 1 Clinical Study in 16 Fasted Healthy Adult Volunteers Receiving 3 Dose Levels of Intranasally Administered Glucagon and One Dose Level of Glucagon Administered by Subcutaneous Injection

The main purpose of this study was to evaluate the safety and tolerability of nasal glucagon (NG). The study drug was delivered into the participant's nostril (intranasally) or was given as an injection just under the skin (subcutaneously) once in each of four study periods. The study lasted about 23 days for each participant.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Nasal Glucagon; Drug: Glucagon

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Mount-Royal, Quebec, Canada, H3P 3P1
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index (BMI) greater than or equal to 20.00 and below or equal to 28.00 kg/m².
• Light-, non- or ex-smokers.
• Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, biochemistry, ECG and urinalysis).

Exclusion Criteria:

• Presence of any nose piercings.
• History of significant hypersensitivity to glucagon or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.
• Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease.
• Presence of clinically significant findings on nasal examination and bilateral anterior rhinoscopy.
• Fasting blood glucose above 5.0 millimoles per liter (mmol/L) at screening, following a 12-hour fasting period.
• Fasting blood glucose assessed with a glucose meter above 5.5 mmol/L 0.5 hour before each dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nasal Glucagon (NG) - 0.5 mg; Ng dose at 0.5 milligram (mg) administered once in one of four study periods.	Drug: Nasal Glucagon; Administered intranasally.; Other Names: LY900018; AMG 504-1
Experimental: NG - 1.0 mg; Ng dose at 1.0 milligram (mg) administered once in one of four study periods.	Drug: Nasal Glucagon; Administered intranasally.; Other Names: LY900018; AMG 504-1
Experimental: NG - 2.0 mg; Ng dose at 2.0 milligram (mg) administered once in one of four study periods.	Drug: Nasal Glucagon; Administered intranasally.; Other Names: LY900018; AMG 504-1
Active Comparator: SC Glucagon 1 mg; Subcutaneous (SC) glucagon dose of 1 mg, in one of four study periods.	Drug: Glucagon; Administered SC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Serious Adverse Event(s) (SAEs)	Safety and tolerability evaluated through the assessment of adverse events. A SAE (serious adverse event) was defined as any untoward medical occurrence in a clinical investigation, which did not necessarily have a causal relationship with this treatment. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.	Baseline through Study Completion (Day 23)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon	Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon	Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon	Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon	Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₄) of Glucose	Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose	Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment
PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax)	Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Locemia Solutions ULC

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 18, 2016
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (Estimate): May 19, 2016

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: August 14, 2019
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: 16424; I8R-MC-IGBD (Other Identifier: Eli Lilly and Company); AMG 101 (Other Identifier: AMG Medical Inc.); GUO-P1-557 (Other Identifier: AMG Medical Inc.)