A Study of Single or Repeated Doses of Glucagon in Participants With Diabetes

A Single Center, Randomized, 4-Period Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Single or Repeated 3 mg Doses of Intranasally Administered Glucagon in Adults With Type 1 or Type 2 Diabetes

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02806973

Enrollment

Registered

2016-06-21

Start date

2015-01-31

Completion date

2015-04-30

Last updated

2019-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Brief summary

This study will investigate how the body processes nasal glucagon (NG) and the effect of nasal glucagon on the body. The study is expected to last about 50 days for each participant. The study is open to adults with type 1 or type 2 diabetes and will last about 50 days.

Interventions

DRUGNasal Glucagon

Administered intranasally.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Male or female with a history of Type 1 or Type 2 insulin-using diabetes of at least 1 year duration (basal only, basal bolus, meal-time only, or twice a day pre-mixed insulin) * A female participant must meet one of the following criteria: * Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the first administration of the study drug, during the study and for at least 30 days after the last dose of the study drug * Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses) * Participant with a body mass index (BMI) greater than or equal to 18.50 kilograms per square meter (kg/m²) and below 35.00 kg/m² * Light-, non- or ex-smokers * 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

Exclusion criteria

* Females who are pregnant, actively attempting to get pregnant, or are lactating * History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (such as 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 * Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases * Known presence of rare hereditary problems of galactose and /or lactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption * Presence of clinically significant findings on nasal examination or bilateral anterior rhinoscopy, such as structural abnormalities, nasal polyps, marked septal deviation, nasal tumors * Nasal surgery in the previous 28 days before Day 1 of this study * Daily use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this study * Any other concomitant maintenance therapy that would influence the outcome of the trial or compromise the safety of the participant, at the discretion of the Investigator and the Sponsor, in the previous 28 days before Day 1 of this study * Significant history of drug dependency or alcohol abuse * Any clinically significant illness in the previous 28 days before Day 1 of this study * Any history of tuberculosis and/or prophylaxis for tuberculosis * Positive urine screening of alcohol and/or drugs of abuse * Positive results to human immunodeficiency virus (HIV) Antigen/Antibody (Ag/Ab) Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or anti-Hepatitis C Virus (HCV (C)) tests * Concurrent participation or intention of participating in another clinical trial during this study * Participants who took an Investigational Product (in another clinical trial) in the previous 28 days before Day 1 of this study or who have already participated in this clinical study * Participants who donated 50 milliliters (mL) or more of blood in the previous 28 days before Day 1 of this study * Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before Day 1 of this study

Design outcomes

Primary

Measure	Time frame
PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon	-0.5, -0.25, 0.00, 0.08, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00 hours after glucagon administration
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T(AUC[0-tlast]) of Baseline-Adjusted Glucagon	-0.5, -0.25, 0.00, 0.08, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00 hours after glucagon administration
PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon	-0.5, -0.25, 0.00, 0.08, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00 hours after glucagon administration
PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax)	-0.5, -0.25, 0.00, 0.08, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00 hours after glucagon administration
Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC0-3) of Baseline-Adjusted Glucose From Time Zero up to 3 Hours	-0.5, -0.25, 0.00, 0.08, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00 hours after glucagon administration
PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose	-0.5, -0.25, 0.00, 0.08, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00 hours after glucagon administration

Other

Measure	Time frame
PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Glucagon	-0.5, -0.25, 0.00, 0.08, 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00 hours after glucagon administration

Countries

Canada

Participant flow

Participants by arm

Arm	Count
Nasal Glucagon All enrolled participants.	32
Total	32

Withdrawals & dropouts

Period	Reason	FG001	FG002	FG003
Period 1	Adverse Event	0	0	1
Period 1	Withdrawal by Subject	2	1	1
Period 3	Adverse Event	0	1	0
Period 3	Withdrawal by Subject	0	0	3

Baseline characteristics

Characteristic	Nasal Glucagon
Age, Continuous	39 years STANDARD_DEVIATION 12
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	28 Participants
Region of Enrollment Canada	32 Participants
Sex: Female, Male Female	11 Participants
Sex: Female, Male Male	21 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	27 / 27	28 / 28	25 / 25	27 / 29
serious Total, serious adverse events	0 / 27	0 / 28	0 / 25	1 / 29