Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia

Phase II Study to Investigate the Safety and Efficacy of 2 Dose Levels of a Novel Glucagon Formulation Compared to Commercially Available Glucagon in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01556594

Acronym

AMG102

Enrollment

Registered

2012-03-16

Start date

2012-03-31

Completion date

2012-07-31

Last updated

2019-09-23

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

Conditions

Hypoglycemia

Keywords

Hypoglycemia, Diabetes mellitus

Brief summary

In this study, participants with Type 1 diabetes received insulin through an infusion into a vein to reduce their blood glucose, and then received nasal glucagon (NG) or glucagon for injection under the skin, and their blood glucose was measured for 3 hours. The main objective of this study was to evaluate the safety and efficacy of intranasal and subcutaneous glucagon (SC) in reversing insulin-induced hypoglycemia in participants with type 1 diabetes.

Detailed description

In the study, up to four (4) treatments were administered as a single dose either intranasally or subcutaneously to eighteen (18) male or female participants under fasting conditions and following the use of insulin to lower blood glucose. The participants were assigned at random to a group that received one treatment for each of the 3 study periods. The glucagon administrations were separated by approximately 7 calendar days. For 2 participants, a single dose of 3 mg NG was administered at the 4th period that was separated by at least 21 calendar days from the 3rd period.

Interventions

DRUGNasal Glucagon 1 mg

DRUGNasal Glucagon 2 mg

DRUGSC Glucagon

DRUGNasal Glucagon 3 mg

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

* History of type 1 diabetes between 2 and 30 years * Receiving daily insulin injections or insulin pump therapy for at least 2 years * If patient is taking Lantus, Levemir or equivalent once-daily in the evening as basal insulin, must be willing to transition to once-daily in the morning at least 48 hours prior to 1st dosing, and to follow this dosing regimen for the entire duration of the study * Body mass index (BMI) greater than or equal to 20.00 and below or equal to 33.00 kg/m2 * Female patients must not be pregnant, and must be using effective contraception. * Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day for at least 3 months before day 1 of this study. An ex smoker is defined as someone who completely stopped smoking for at least 6 months before day 1 of this study

Exclusion criteria

* History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the previous 6 months before day 1 of this study * Score ≥4 on the Clarke Hypoglycemia Awareness survey at screening * Presence or history of pheochromocytoma (i.e. adrenal gland tumor) * Presence or history of significant upper respiratory or allergic (i.e., seasonal rhinitis) disease * Presence of clinically significant findings on nasal examination and bilateral anterior rhinoscopy * Known presence of hereditary problems of galactose and /or lactose intolerance * History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (like angioedema) to any drugs

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Responders	Pre-dose; 30 minutes following glucagon administration	Participants with a blood glucose increment of ≥1.5 millimole per liter \[mmol/L) within 15 of nadir (5 minutes post dose) and for at least 10 minutes following nadir.
Number of Participants With at Least One Adverse Event	Within 3 hours post glucagon administration	Safety and tolerability evaluated through the assessment of adverse events. An AE was defined as any untoward medical occurrence in a clinical investigation subject administered the investigational product and which did not necessarily have a causal relationship with this treatment. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Secondary

Measure	Time frame
Maximum Change From Baseline Concentration (Cmax) of Glucagon	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration
Maximum Concentration (Cmax) of Baseline-Adjusted Glucose	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration
Area Under the Curve (AUC0-last) of Baseline Adjusted Glucagon	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration
Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration
Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose	Pre-dose; 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration

Countries

Canada

Participant flow

Recruitment details

Participants were recruited from the clinical site's database and from participants who responded to advertising in local media.

Participants by arm

Arm	Count
Treatment Group 1 NG dose of 1 mg and 2 mg. SC glucagon dose of 1mg.	10
Treatment Group 2 NG dose of 1 mg, 2 mg and 3mg. SC glucagon dose of 1mg.	2
Treatment Group 3 NG dose of 2 mg and 3mg. SC glucagon dose of 1mg.	6
Total	18

Baseline characteristics

Characteristic	Treatment Group 2	Treatment Group 3	Treatment Group 1	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	2 Participants	6 Participants	10 Participants	18 Participants
Age, Continuous	42 years STANDARD_DEVIATION 2	25 years STANDARD_DEVIATION 6	34 years STANDARD_DEVIATION 14	32 years STANDARD_DEVIATION 12
Region of Enrollment Canada	2 Participants	6 Participants	10 Participants	18 Participants
Sex: Female, Male Female	0 Participants	1 Participants	4 Participants	5 Participants
Sex: Female, Male Male	2 Participants	5 Participants	6 Participants	13 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	16 / 18	9 / 12	15 / 18	8 / 8
serious Total, serious adverse events	0 / 18	0 / 12	0 / 18	0 / 8

Outcome results

Primary

Number of Participants With at Least One Adverse Event

Safety and tolerability evaluated through the assessment of adverse events. An AE was defined as any untoward medical occurrence in a clinical investigation subject administered the investigational product and which did not necessarily have a causal relationship with this treatment. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Time frame: Within 3 hours post glucagon administration

Population: Participants who received at least one dose of glucagon (SC Glucagon or NG).

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SC Glucagon	Number of Participants With at Least One Adverse Event	16 Participants
NG 1 mg	Number of Participants With at Least One Adverse Event	9 Participants
NG 2 mg	Number of Participants With at Least One Adverse Event	15 Participants
NG 3 mg	Number of Participants With at Least One Adverse Event	8 Participants

Primary

Percentage of Responders

Participants with a blood glucose increment of ≥1.5 millimole per liter \[mmol/L) within 15 of nadir (5 minutes post dose) and for at least 10 minutes following nadir.

Time frame: Pre-dose; 30 minutes following glucagon administration

Population: All enrolled participants.

Arm	Measure	Value (NUMBER)
SC Glucagon	Percentage of Responders	83.3 percentage of participants
NG 1 mg	Percentage of Responders	25 percentage of participants
NG 2 mg	Percentage of Responders	50 percentage of participants
NG 3 mg	Percentage of Responders	75 percentage of participants

Secondary