Trial Outcomes & Findings for A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus (NCT NCT03421379)
NCT ID: NCT03421379
Last Updated: 2019-10-08
Results Overview
Percentage of participants who achieved treatment success during the controlled insulin-induced hypoglycemia in participants with type 1 diabetes mellitus (T1DM) and participants with type 2 diabetes mellitus (T2DM).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
PHASE3
Target enrollment
75 participants
Primary outcome timeframe
Pre-dose up to 30 minutes post each glucagon administration
Results posted on
2019-10-08
Participant Flow
Participants were randomized to receive either nasal glucagon or intramuscular (IM) glucagon in the first period, followed by the alternate treatment in the second period.
Participant milestones
| Measure |
Glucagon Nasal Powder/Glucagon Hydrochloride
A single dose of 3 milligram (mg) glucagon nasal powder was administered intranasally in period 1 then 1 mg single dose intramuscular glucagon hydrochloride solution was administered in period 2.
|
Glucagon Hydrochloride Solution/Glucagon Nasal Powder
A single dose of 1 mg glucagon hydrochloride solution was administered intramuscular (IM) in period 1 then 3 mg single dose glucagon nasal powder was administered in period 2.
|
|---|---|---|
|
Period 1
STARTED
|
34
|
41
|
|
Period 1
Received at Least One Dose of Study Drug
|
33
|
39
|
|
Period 1
COMPLETED
|
32
|
37
|
|
Period 1
NOT COMPLETED
|
2
|
4
|
|
Washout Period (3 to 14 Days)
STARTED
|
32
|
37
|
|
Washout Period (3 to 14 Days)
COMPLETED
|
32
|
37
|
|
Washout Period (3 to 14 Days)
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
32
|
37
|
|
Period 2
COMPLETED
|
32
|
37
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Glucagon Nasal Powder/Glucagon Hydrochloride
A single dose of 3 milligram (mg) glucagon nasal powder was administered intranasally in period 1 then 1 mg single dose intramuscular glucagon hydrochloride solution was administered in period 2.
|
Glucagon Hydrochloride Solution/Glucagon Nasal Powder
A single dose of 1 mg glucagon hydrochloride solution was administered intramuscular (IM) in period 1 then 3 mg single dose glucagon nasal powder was administered in period 2.
|
|---|---|---|
|
Period 1
Withdrawal by Subject
|
0
|
1
|
|
Period 1
Physician Decision
|
1
|
1
|
|
Period 1
Did not receive treatment
|
1
|
2
|
Baseline Characteristics
A Study of Nasal Glucagon (LY900018) in Japanese Participants With Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Glucagon Nasal Powder/Glucagon Hydrochloride Solution
n=33 Participants
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution/Glucagon Nasal Powder
n=39 Participants
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
Total
n=72 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.7 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
57.5 years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
50.2 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
33 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
33 participants
n=5 Participants
|
39 participants
n=7 Participants
|
72 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose up to 30 minutes post each glucagon administrationPopulation: All randomized participant who completed both treatment visits and had evaluable treatment success data.
Percentage of participants who achieved treatment success during the controlled insulin-induced hypoglycemia in participants with type 1 diabetes mellitus (T1DM) and participants with type 2 diabetes mellitus (T2DM).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.
Outcome measures
| Measure |
Glucagon Nasal Powder
n=68 Participants
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution
n=68 Participants
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
|---|---|---|
|
Percentage of Participants Achieving Treatment Success During Controlled Insulin-Induced Hypoglycemia
|
100 percentage of participants
|
100 percentage of participants
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administrationPopulation: All randomized patients who receive at least 1 dose of the study drug and have evaluable PD data.
PD assessment measured the change from Baseline in maximal blood glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride intramuscular (IM).
Outcome measures
| Measure |
Glucagon Nasal Powder
n=71 Participants
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution
n=70 Participants
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
|---|---|---|
|
Pharmacodynamics (PD): Change From Baseline in Maximal Blood Glucose (BGmax) of Glucagon Nasal Powder and Glucagon Hydrochloride Intramuscular (IM)
|
113 milligram/deciliter (mg/dL)
Geometric Coefficient of Variation 32
|
119 milligram/deciliter (mg/dL)
Geometric Coefficient of Variation 33
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administrationPopulation: All randomized participants who received at least one dose of study drug and had evaluable PD data.
PD assessment measured the time to maximal concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM.
Outcome measures
| Measure |
Glucagon Nasal Powder
n=71 Participants
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution
n=70 Participants
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
|---|---|---|
|
PD: Time to Maximal Concentration (Tmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM
|
1.00 hour
Interval 0.5 to 4.02
|
1.50 hour
Interval 0.67 to 4.0
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administrationPopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data.
PK assessment measured the change from baseline in the area under the concentration versus time curve from time zero to time t, where t is the last time point with a measurable concentration of Glucagon Nasal Powder and Glucagon Hydrochloride IM.
Outcome measures
| Measure |
Glucagon Nasal Powder
n=71 Participants
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution
n=68 Participants
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
|---|---|---|
|
Pharmacokinetics (PK): Change From Baseline in Area Under the Concentration Versus Time Curve From Zero to Time t (AUC [0-tLast]) of Glucagon Nasal Powder and Glucagon Hydrochloride IM
|
4830 Picogram*hour/milliliter (pg*h/mL)
Geometric Coefficient of Variation 89
|
3240 Picogram*hour/milliliter (pg*h/mL)
Geometric Coefficient of Variation 32
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administrationPopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data.
PK assessment measured the change from baseline in maximal concentration (Cmax) of glucagon nasal powder and glucagon hydrochloride IM.
Outcome measures
| Measure |
Glucagon Nasal Powder
n=71 Participants
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution
n=68 Participants
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
|---|---|---|
|
PK: Change From Baseline in Maximal Concentration (Cmax) of Glucagon Nasal Powder and Glucagon Hydrochloride IM
|
9520 picogram/milliliter (pg/mL)
Geometric Coefficient of Variation 103
|
3290 picogram/milliliter (pg/mL)
Geometric Coefficient of Variation 37
|
SECONDARY outcome
Timeframe: Pre-dose, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 240 minutes after each glucagon administrationPopulation: All randomized participants who received at least one dose of study drug and had evaluable PK data.
PK assessment measured the change from baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM.
Outcome measures
| Measure |
Glucagon Nasal Powder
n=71 Participants
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution
n=68 Participants
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
|---|---|---|
|
PK: Change From Baseline in Tmax of Glucagon Nasal Powder and Glucagon Hydrochloride IM
|
0.25 hour (h)
Interval 0.17 to 0.67
|
0.17 hour (h)
Interval 0.08 to 0.67
|
Adverse Events
Glucagon Nasal Powder
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Glucagon Hydrochloride Solution
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Glucagon Nasal Powder
n=71 participants at risk
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution
n=70 participants at risk
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/71 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
Other adverse events
| Measure |
Glucagon Nasal Powder
n=71 participants at risk
A single dose of 3 mg glucagon nasal powder was administered intranasally
|
Glucagon Hydrochloride Solution
n=70 participants at risk
A single dose of 1 mg glucagon hydrochloride solution was administered IM
|
|---|---|---|
|
Eye disorders
Eye pain
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Ear and labyrinth disorders
Ear pain
|
2.8%
2/71 • Number of events 2 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Eye disorders
Eye pruritus
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Eye disorders
Lacrimation increased
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
7.0%
5/71 • Number of events 5 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
15.7%
11/70 • Number of events 11 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Toothache
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
2.8%
2/71 • Number of events 2 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
5.7%
4/70 • Number of events 5 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
General disorders
Feeling abnormal
|
0.00%
0/71 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Infections and infestations
Cystitis
|
0.00%
0/71 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Investigations
Blood pressure decreased
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
2.9%
2/70 • Number of events 2 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Investigations
Blood pressure increased
|
5.6%
4/71 • Number of events 4 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal pruritus
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.4%
1/71 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinalgia
|
8.5%
6/71 • Number of events 6 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
0.00%
0/70 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.00%
0/71 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Vascular disorders
Hot flush
|
0.00%
0/71 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Vascular disorders
Hypertension
|
0.00%
0/71 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
|
Vascular disorders
Peripheral coldness
|
0.00%
0/71 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
1.4%
1/70 • Number of events 1 • From Baseline to End of Follow-up (Up to 2 Months)
All randomized participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60