A Study of Nasal Glucagon in Participants With a Common Cold

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02778100
• Collaborator: Locemia Solutions ULC (Industry)
• Enrollment: 36
• Location: 1
• Arms: 3
• Duration (Months): 1
• Patients Per Site Per Month: 35.3

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the safety of nasal glucagon (NG) in participants with a common cold, some of whom will also take a nasal decongestant. The study will investigate how the body processes NG and the effect of NG on the body. The study will last up to 30 days for each participant.

Condition or Disease	Intervention/Treatment	Phase
Common Cold	Drug: Nasal Glucagon; Drug: Oxymetazoline	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1 Study to Evaluate the Effects of Common Cold and of Concomitant Administration of Nasal Decongestant on the Pharmacokinetics and Pharmacodynamics of a Novel Glucagon Formulation in Otherwise Healthy Subjects
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nasal Glucagon (NG) - Common Cold Cohort 1 - Nasal Glucagon (NG) administered once in participants with a common cold.	Drug: Nasal Glucagon; Administered intranasally.; Other Names: LY900018 AMG 504-1
Experimental: Nasal Glucagon (NG) - Symptom-Free Cohort 1 - NG administered once in participants who have recovered from a common cold.	Drug: Nasal Glucagon; Administered intranasally.; Other Names: LY900018 AMG 504-1
Experimental: NG - Common Cold+Oxymetazoline Cohort 2 - NG administered once in participants with a common cold who are taking oxymetazoline.	Drug: Nasal Glucagon; Administered intranasally.; Other Names: LY900018 AMG 504-1 ; Drug: Oxymetazoline; Administered intranasally.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) [Baseline up to Study Completion (Day 30)]

   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 participant administered the investigational product and 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.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) 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]

2. PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) 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]

3. PK: 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]

4. PK: 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]

5. Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC0-3) of Baseline-Adjusted Glucose From Time Zero up to 3 Hours [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]

6. PD: 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]

7. PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax) 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female participant presenting a score of 2 or 3 on nasal congestion and/or nasal discharge associated with at least one other symptom of common cold, as determined by the 8-item Jackson cold scale at screening and prior to dosing of period

• Participant with a body mass index (BMI) greater than or equal to 18.50 and below 30.00 kilogram per square meter (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, electrocardiogram [ECG] and urinalysis).

Exclusion Criteria:

• Presence of any nose piercings.

• History of significant hypersensitivity to glucagon, oxymetazoline 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 severe fever (more than 39.5 degrees Celsius) at screening or prior to dosing of period 1.

• Presence of clinically significant findings on nasal examination or bilateral anterior rhinoscopy, such as structural abnormalities, nasal polyps, marked septal deviation, nasal tumors.

• Presence or history of Type 1 or Type 2 diabetes.

• Presence or history of significant hypoglycemia or hyperglycemia.

• Use of beta-blockers, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before day 1 of the study.

• Fasting blood glucose above 6.1 mmol/L at screening, following a 12-hour fasting period.

• Fasting blood glucose assessed with a glucose meter above 6.1 mmol/L approximately 0.5 hour before each dosing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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.	Mount-Royal	Quebec	Canada	H3P 3P1

Sponsors and Collaborators

• Eli Lilly and Company
• Locemia Solutions ULC

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02778100
• Other Study ID Numbers: 16425; GUO-P2-628; AMG 104; I8R-MC-IGBE
• First Posted: May 19, 2016
• Last Update Posted: Sep 18, 2019
• Last Verified: May 1, 2016

• Additional relevant MeSH terms: Common Cold; Phenylephrine; Oxymetazoline; Glucagon

Study Results

Participant Flow

Arm/Group Title	Nasal Glucagon (NG) 3 mg (Milligram)	NG 3 mg Plus Oxymetazoline
Arm/Group Description	Period 1: NG administered once in participants with a common cold. Period 2: NG administered once in participants who have recovered from a common cold.	Period 1 only: NG administered once to participants with a common cold, who are taking oxymetazoline.
Period Title: Period 1 (Common Cold)
STARTED	18	18
COMPLETED	17	18
NOT COMPLETED	1	0
Period Title: Period 1 (Common Cold)
STARTED	17	0
COMPLETED	17	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Nasal Glucagon (NG)	NG Plus Oxymetazoline	Total
Arm/Group Description	Dose of 3 mg NG administered once to participants with a common cold.	Dose of 3 mg NG administered once to participants with a common cold, who are taking oxymetazoline.	Total of all reporting groups
Overall Participants	18	18	36
Age (years) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [years]	32	29	30.5
Sex: Female, Male (Count of Participants)
Female	9 50%	10 55.6%	19 52.8%
Male	9 50%	8 44.4%	17 47.2%
Race/Ethnicity, Customized (Count of Participants)
Black	2 11.1%	3 16.7%	5 13.9%
White	16 88.9%	14 77.8%	30 83.3%
Other	0 0%	1 5.6%	1 2.8%
Region of Enrollment (Count of Participants)
Canada	18 100%	18 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With One or More Serious Adverse Event(s) (SAEs)
Description	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 participant administered the investigational product and 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.
Time Frame	Baseline up to Study Completion (Day 30)

Outcome Measure Data

Analysis Population Description

All enrolled participants.

Arm/Group Title	NG - Common Cold	NG - Symptom-Free	NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg NG administered once in participants with a common cold.	Dose of 3 mg NG administered once in participants who have recovered from a common cold.	Dose of 3 mg NG administered once in participants with a common cold who are taking oxymetazoline.
Measure Participants	18	17	18
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants with evaluable PK data.

Arm/Group Title	NG - Common Cold	NG - Symptom-Free	NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg NG administered once in participants with a common cold.	Dose of 3 mg NG administered once in participants who have recovered from a common cold.	Dose of 3 mg NG administered once in participants with a common cold who are taking oxymetazoline.
Measure Participants	18	17	18
Mean (Standard Deviation) [picogram*hour per millilitre (pg*hr/mL)]	1039.7 (1020.81)	631.8 (399.66)	868.4 (622.39)

3. Secondary Outcome

Title	PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants with evaluable PK data.

Arm/Group Title	NG - Common Cold	NG - Symptom-Free	NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg NG administered once in participants with a common cold.	Dose of 3 mg NG administered once in participants who have recovered from a common cold.	Dose of 3 mg NG administered once in participants with a common cold who are taking oxymetazoline.
Measure Participants	18	17	18
Mean (Standard Deviation) [pg*hr/mL]	1108.9 (1055)	669.3 (431.7)	1064.3 (838.4)

4. Secondary Outcome

Title	PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants with evaluable PK data.

Arm/Group Title	NG - Common Cold	NG - Symptom-Free	NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg NG administered once in participants with a common cold.	Dose of 3 mg NG administered once in participants who have recovered from a common cold.	Dose of 3 mg NG administered once in participants with a common cold who are taking oxymetazoline.
Measure Participants	18	17	18
Median (Full Range) [Hour (hr)]	0.3	0.3	0.3

5. Secondary Outcome

Title	PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants with evaluable PK data.

Arm/Group Title	NG - Common Cold	NG - Symptom-Free	NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg NG administered once in participants with a common cold.	Dose of 3 mg NG administered once in participants who have recovered from a common cold.	Dose of 3 mg NG administered once in participants with a common cold who are taking oxymetazoline.
Measure Participants	18	17	18
Mean (Standard Deviation) [picograms per millilitre (pg/mL)]	1145.4 (994.43)	745.6 (548.42)	811.5 (597.51)

6. Secondary Outcome

Title	Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC0-3) of Baseline-Adjusted Glucose From Time Zero up to 3 Hours
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants with evaluable PD data.

Arm/Group Title	NG - Common Cold	NG - Symptom-Free	NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg NG administered once in participants with a common cold.	Dose of 3 mg NG administered once in participants who have recovered from a common cold.	Dose of 3 mg NG administered once in participants with a common cold who are taking oxymetazoline.
Measure Participants	18	17	18
Mean (Standard Deviation) [Hour*millimoles per liter(hr*mmol/L)]	4.3 (2.11)	3.8 (1.92)	4.2 (2.06)

7. Secondary Outcome

Title	PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants with evaluable PD data.

Arm/Group Title	NG - Common Cold	NG - Symptom-Free	NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg NG administered once in participants with a common cold.	Dose of 3 mg NG administered once in participants who have recovered from a common cold.	Dose of 3 mg NG administered once in participants with a common cold who are taking oxymetazoline.
Measure Participants	18	17	18
Median (Full Range) [Millimoles per liter (mmol/L)]	0.5	0.6	0.7

8. Secondary Outcome

Title	PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax) of Baseline-Adjusted Glucose
Time Frame	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

Outcome Measure Data

Analysis Population Description

All enrolled participants with evaluable PD data.

Arm/Group Title	NG - Common Cold	NG - Symptom-Free	NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg NG administered once in participants with a common cold.	Dose of 3 mg NG administered once in participants who have recovered from a common cold.	Dose of 3 mg NG administered once in participants with a common cold who are taking oxymetazoline.
Measure Participants	18	17	18
Mean (Standard Deviation) [Millimoles per liter (mmol/L)]	2.9 (1.57)	2.7 (1.38)	3.4 (1.42)

Adverse Events

Time Frame	First dose of study drug (Day 1) until post-study completion (Day 30).
Arm/Group Title	NG- Common Cold		NG - Symptom-Free		NG - Common Cold+Oxymetazoline
Arm/Group Description	Dose of 3 mg nasal glucagon (NG) administered once in participants with a common cold.		Dose of 3 mg nasal glucagon (NG) administered once in participants who have recovered from a common cold.		Dose of 3 mg nasal glucagon (NG) administered once in participants with a common cold who are taking oxymetazoline.
All Cause Mortality
	NG- Common Cold		NG - Symptom-Free		NG - Common Cold+Oxymetazoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	NG- Common Cold		NG - Symptom-Free		NG - Common Cold+Oxymetazoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/17 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	NG- Common Cold		NG - Symptom-Free		NG - Common Cold+Oxymetazoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/18 (100%)		17/17 (100%)		18/18 (100%)
Cardiac disorders
Palpitations	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Ear and labyrinth disorders
Ear pruritus	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Eye disorders
Abnormal sensation in eye	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Eye pain	1/18 (5.6%)	1	0/17 (0%)	0	2/18 (11.1%)	2
Eye pruritus	5/18 (27.8%)	5	0/17 (0%)	0	5/18 (27.8%)	5
Eye swelling	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Lacrimation increased	13/18 (72.2%)	17	12/17 (70.6%)	13	12/18 (66.7%)	16
Ocular hyperaemia	7/18 (38.9%)	7	7/17 (41.2%)	7	8/18 (44.4%)	12
Gastrointestinal disorders
Abdominal pain	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Abdominal pain upper	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Diarrhoea	2/18 (11.1%)	2	0/17 (0%)	0	0/18 (0%)	0
Dry mouth	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Nausea	8/18 (44.4%)	10	2/17 (11.8%)	2	7/18 (38.9%)	7
Vomiting	1/18 (5.6%)	2	0/17 (0%)	0	5/18 (27.8%)	7
General disorders
Administration site reaction	0/18 (0%)	0	1/17 (5.9%)	1	0/18 (0%)	0
Asthenia	2/18 (11.1%)	2	0/17 (0%)	0	1/18 (5.6%)	1
Chills	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Facial pain	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Fatigue	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Feeling cold	2/18 (11.1%)	2	0/17 (0%)	0	0/18 (0%)	0
Feeling hot	0/18 (0%)	0	1/17 (5.9%)	1	0/18 (0%)	0
Sensation of pressure	0/18 (0%)	0	0/17 (0%)	0	2/18 (11.1%)	2
Injury, poisoning and procedural complications
Administration related reaction	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Procedural complication	0/18 (0%)	0	1/17 (5.9%)	1	0/18 (0%)	0
Investigations
Blood glucose decreased	0/18 (0%)	0	1/17 (5.9%)	1	0/18 (0%)	0
Neutrophil count increased	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
White blood cell count increased	0/18 (0%)	0	1/17 (5.9%)	1	0/18 (0%)	0
Nervous system disorders
Burning sensation	0/18 (0%)	0	1/17 (5.9%)	1	0/18 (0%)	0
Disturbance in attention	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Dizziness	4/18 (22.2%)	5	5/17 (29.4%)	6	5/18 (27.8%)	5
Dysgeusia	0/18 (0%)	0	1/17 (5.9%)	1	2/18 (11.1%)	2
Headache	4/18 (22.2%)	4	3/17 (17.6%)	3	5/18 (27.8%)	5
Paraesthesia	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Parosmia	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Somnolence	6/18 (33.3%)	6	3/17 (17.6%)	3	1/18 (5.6%)	1
Tremor	0/18 (0%)	0	1/17 (5.9%)	1	0/18 (0%)	0
Vision blurred	0/18 (0%)	0	0/17 (0%)	0	1/18 (5.6%)	1
Psychiatric disorders
Confusional state	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Self-induced vomiting	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/18 (5.6%)	1	0/17 (0%)	0	0/18 (0%)	0
Epistaxis	1/18 (5.6%)	1	1/17 (5.9%)	1	0/18 (0%)	0
Nasal congestion	5/18 (27.8%)	5	3/17 (17.6%)	3	4/18 (22.2%)	4
Nasal discomfort	12/18 (66.7%)	15	7/17 (41.2%)	7	15/18 (83.3%)	15
Rhinorrhoea	10/18 (55.6%)	10	5/17 (29.4%)	6	14/18 (77.8%)	15
Sneezing	5/18 (27.8%)	5	3/17 (17.6%)	3	3/18 (16.7%)	3
Throat irritation	0/18 (0%)	0	1/17 (5.9%)	2	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Rash	1/18 (5.6%)	2	0/17 (0%)	0	0/18 (0%)	0
Vascular disorders
Hot flush	2/18 (11.1%)	2	0/17 (0%)	0	0/18 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.