Trial Outcomes & Findings for A Study of Nasal Glucagon in Participants With Type 1 Diabetes Mellitus (NCT NCT03339453)

Last Updated: 2019-09-23

Results Overview

Treatment success is defined as an increase in plasma glucose to greater than or equal to (≥) 70 milligrams per deciliter (mg/dL) or an increase of ≥20 mg/dL from plasma glucose nadir, without receiving additional actions to increase the plasma glucose concentration. Nadir is defined as the minimum plasma glucose concentration at the time of or within 10 minutes following glucagon administration.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

70 participants

Primary outcome timeframe

Pre-dose up to 30 minutes post each glucagon administration

Results posted on

2019-09-23

Participant Flow

In each period, either 3 milligram (mg) nasal glucagon (NG) or 1 mg intramuscular (IM) Glucagon was administered. After a wash-out period of at least 1 day (24 hours) from the first period (first visit), participants crossed over to the alternate glucagon treatment in period 2 (second visit).

Participant milestones

Participant milestones
Measure	NG 1st/IM Glucagon 2nd Participants received 3 mg of NG at the first treatment visit followed by 1 mg of IM glucagon at the second treatment visit.	IM Glucagon 1st/NG 2nd Participants received 1 mg of IM glucagon at the first treatment visit followed by 3 mg of NG at the second treatment visit.
First Visit of Glucagon Treatment STARTED	35	35
First Visit of Glucagon Treatment Received at Least 1 Dose of Study Drug	35	35
First Visit of Glucagon Treatment COMPLETED	35	34
First Visit of Glucagon Treatment NOT COMPLETED	0	1
Second Visit for Alternate Glucagon STARTED	35	34
Second Visit for Alternate Glucagon COMPLETED	35	34
Second Visit for Alternate Glucagon NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	NG 1st/IM Glucagon 2nd Participants received 3 mg of NG at the first treatment visit followed by 1 mg of IM glucagon at the second treatment visit.	IM Glucagon 1st/NG 2nd Participants received 1 mg of IM glucagon at the first treatment visit followed by 3 mg of NG at the second treatment visit.
First Visit of Glucagon Treatment Adverse Event	0	1

Baseline Characteristics

A Study of Nasal Glucagon in Participants With Type 1 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glucagon n=70 Participants All enrolled participants who received either 3 mg NG or 1 mg IM Glucagon.
Age, Continuous	41.7 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	70 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	70 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Germany	70 participants n=5 Participants
Weight	78.79 Kilogram (kg) STANDARD_DEVIATION 13.28 • n=5 Participants
Height	175.21 Centimeter (cm) STANDARD_DEVIATION 8.43 • n=5 Participants
Body Mass Index (BMI)	25.53 kilogram per square meter (kg/m2) STANDARD_DEVIATION 2.97 • n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose up to 30 minutes post each glucagon administration

Population: All participants who completed both treatment visits with evaluable data.

Outcome measures

Outcome measures
Measure	Nasal Glucagon (NG) n=66 Participants Dose of 3 mg nasal glucagon.	IM Glucagon n=66 Participants Dose of 1 mg IM glucagon.
Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia	66 Participants	66 Participants

SECONDARY outcome

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

Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PD data.

Outcome measures

Outcome measures
Measure	Nasal Glucagon (NG) n=68 Participants Dose of 3 mg nasal glucagon.	IM Glucagon n=69 Participants Dose of 1 mg IM glucagon.
Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax)	132 Milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 36	161 Milligrams per deciliter (mg/dL) Geometric Coefficient of Variation 29

SECONDARY outcome

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

Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PD data.

Outcome measures

Outcome measures
Measure	Nasal Glucagon (NG) n=68 Participants Dose of 3 mg nasal glucagon.	IM Glucagon n=69 Participants Dose of 1 mg IM glucagon.
PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose	1.00 Hour (hr) Interval 0.42 to 1.5	1.50 Hour (hr) Interval 0.83 to 1.5

SECONDARY outcome

Timeframe: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration

Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PK data.

Outcome measures

Outcome measures
Measure	Nasal Glucagon (NG) n=63 Participants Dose of 3 mg nasal glucagon.	IM Glucagon n=66 Participants Dose of 1 mg IM glucagon.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC[0-tlast]) of Baseline Adjusted Glucagon	2740 picogramhour per millilitre (pghr/mL) Geometric Coefficient of Variation 68	3320 picogramhour per millilitre (pghr/mL) Geometric Coefficient of Variation 40

SECONDARY outcome

Timeframe: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration

Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PK data.

Outcome measures

Outcome measures
Measure	Nasal Glucagon (NG) n=63 Participants Dose of 3 mg nasal glucagon.	IM Glucagon n=66 Participants Dose of 1 mg IM glucagon.
PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon	6130 picograms per millilitre (pg/mL) Geometric Coefficient of Variation 74	3750 picograms per millilitre (pg/mL) Geometric Coefficient of Variation 44

SECONDARY outcome

Timeframe: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, and 240 minutes after glucagon administration

Population: All enrolled participants who received at least 1 dose of the study drug with evaluable PK data.

Outcome measures

Outcome measures
Measure	Nasal Glucagon (NG) n=63 Participants Dose of 3 mg nasal glucagon.	IM Glucagon n=66 Participants Dose of 1 mg IM glucagon.
PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon	0.25 Hour (hr) Interval 0.17 to 0.5	0.25 Hour (hr) Interval 0.08 to 0.5

Adverse Events

Nasal Glucagon (NG)

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Intramuscular (IM) Glucagon

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Nasal Glucagon (NG) n=70 participants at risk Dose of 3 mg nasal glucagon.	Intramuscular (IM) Glucagon n=69 participants at risk Dose of 1 mg intramuscular glucagon.
Eye disorders Eye pain	1.4% 1/70 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).	0.00% 0/69 • First dose of study drug (Day 1) until post-study completion (Day 30).
Eye disorders Ocular discomfort	1.4% 1/70 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).	0.00% 0/69 • First dose of study drug (Day 1) until post-study completion (Day 30).
Gastrointestinal disorders Abdominal discomfort	1.4% 1/70 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).	0.00% 0/69 • First dose of study drug (Day 1) until post-study completion (Day 30).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/70 • First dose of study drug (Day 1) until post-study completion (Day 30).	1.4% 1/69 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).
Gastrointestinal disorders Diarrhoea	0.00% 0/70 • First dose of study drug (Day 1) until post-study completion (Day 30).	1.4% 1/69 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).
Gastrointestinal disorders Nausea	31.4% 22/70 • Number of events 22 • First dose of study drug (Day 1) until post-study completion (Day 30).	42.0% 29/69 • Number of events 29 • First dose of study drug (Day 1) until post-study completion (Day 30).
Gastrointestinal disorders Vomiting	14.3% 10/70 • Number of events 10 • First dose of study drug (Day 1) until post-study completion (Day 30).	17.4% 12/69 • Number of events 12 • First dose of study drug (Day 1) until post-study completion (Day 30).
Infections and infestations Nasopharyngitis	5.7% 4/70 • Number of events 4 • First dose of study drug (Day 1) until post-study completion (Day 30).	2.9% 2/69 • Number of events 2 • First dose of study drug (Day 1) until post-study completion (Day 30).
Infections and infestations Otitis media	0.00% 0/70 • First dose of study drug (Day 1) until post-study completion (Day 30).	1.4% 1/69 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).
Investigations Body temperature increased	0.00% 0/70 • First dose of study drug (Day 1) until post-study completion (Day 30).	1.4% 1/69 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).
Nervous system disorders Headache	15.7% 11/70 • Number of events 13 • First dose of study drug (Day 1) until post-study completion (Day 30).	10.1% 7/69 • Number of events 7 • First dose of study drug (Day 1) until post-study completion (Day 30).
Respiratory, thoracic and mediastinal disorders Cough	1.4% 1/70 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).	0.00% 0/69 • First dose of study drug (Day 1) until post-study completion (Day 30).
Respiratory, thoracic and mediastinal disorders Epistaxis	1.4% 1/70 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).	0.00% 0/69 • First dose of study drug (Day 1) until post-study completion (Day 30).
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.00% 0/70 • First dose of study drug (Day 1) until post-study completion (Day 30).	1.4% 1/69 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.9% 2/70 • Number of events 2 • First dose of study drug (Day 1) until post-study completion (Day 30).	0.00% 0/69 • First dose of study drug (Day 1) until post-study completion (Day 30).
Skin and subcutaneous tissue disorders Hyperhidrosis	1.4% 1/70 • Number of events 1 • First dose of study drug (Day 1) until post-study completion (Day 30).	0.00% 0/69 • First dose of study drug (Day 1) until post-study completion (Day 30).