Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01994746
• Collaborator: T1D Exchange Clinic Network Coordinating Center (Other), Locemia Solutions ULC (Industry)
• Enrollment: 77
• Locations: 8
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 9.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of 3 milligrams (mg) glucagon (glucagon nasal powder) administered nasally compared with commercially available glucagon given by intramuscular injection.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Nasal Glucagon; Drug: Intramuscular Glucagon	Phase 3

Detailed Description

Each glucagon dosing visit was conducted after an overnight fast of at least 8 h with a starting plasma glucose >= 90 mg/dL. Hypoglycemia was induced by an intravenous (IV) infusion of regular insulin diluted in normal saline during the clinic visit. Five minutes after stopping the insulin infusion (once the plasma glucose was <60 mg/dL), participants were treated with either a 3 mg glucagon dose nasally or 1 mg of glucagon administered by intramuscular (IM) injection.

After a wash-out period of 7 days or more, participants returned to the clinic and the procedure repeated with each participant crossed over to the other treatment. As such, each participant underwent two episodes of insulin-induced hypoglycemia in random order and received glucagon nasal powder during one episode and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other episode.

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Nasal Glucagon for Treatment of Insulin Induced Hypoglycemia in Adults With Diabetes
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nasal Glucagon At one visit, a glucagon dose of 3 mg was administered in a nostril with a prefilled delivery device that delivers a single dose upon activation.	Drug: Nasal Glucagon; Other Names: AMG504-1 LY900018
Active Comparator: Intramuscular Glucagon At a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular [IM]).	Drug: Intramuscular Glucagon; Other Names: GlucaGen HypoKit

Outcome Measures

Primary Outcome Measures

1. Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir [Within 30 minutes after receiving glucagon at both dosing visits (glucose was measured at pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration)]

   Increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level defines treatment success. Due to the residual activity of circulating insulin, glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes following glucagon administration.

Secondary Outcome Measures

1. Nasal and Non-nasal Effects/Symptoms [Pre-dose; 15, 30, 60, and 90 post glucagon administration]

   Symptoms of runny nose, nasal congestion and/or itching, sneezing, watery and/or itchy eyes, redness of eyes, and itching of ears and/or throat were assessed. This was done via the "Nasal Non-nasal Score Questionnaire". Each of the 9 symptoms is assigned an integer value from 0 to 3; higher values indicate more severe symptoms (a score of 0 indicates no symptoms). The reported results indicate the cohort median out of a possible maximum value of 27 (summing all 9 questions for each subject and reporting the median/IQR across participants).

2. Recovery From Symptoms of Hypoglycemia [Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon]

   Recovery from hypoglycemia symptoms were assessed using the Edinburgh Hypoglycemia Scale. The Edinburgh Hypoglycemia Symptom Scale measures the intensity of 15 commonly experienced hypoglycemic symptoms on a 7-point Likert scale (1 = not present, 7 = very intense). The higher the score, the more intense the hypoglycemia symptoms. The sum of each symptom score would yield a range of 15 to 105 (i.e., 15 x 7 =105). The total score was calculated as the sum of each symptom score minus 15, and summarized at each time point by treatment group.

3. Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir [Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration]

   The mean time from glucagon administration to blood glucose >/=70 mg/dL or an increase ≥20 mg/dL in blood glucose from nadir.

4. Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon [Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration]

5. Maximum Change From Baseline Concentration (Cmax) of Glucagon [Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration]

6. Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon [Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration]

7. Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes [Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration]

8. Maximum Change From Baseline Concentration (Cmax) of Glucose [Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration]

9. Time to Maximum Change From Baseline Concentration (Tmax) of Glucose [Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

To be eligible, the following inclusion criteria must be met:

• Clinical diagnosis of either type 1 diabetes receiving daily insulin since the time of diagnosis for at least 2 years or type 2 diabetes receiving multiple daily insulin doses for at least 2 years

• At least 18.0 years of age and less than 65.0 years

• Body mass index (BMI) greater than or equal to 20.0 and below or equal to 35.0 kilograms per meter squared (kg/m²)

• Weighs at least 50 kg (110 pounds)

• Females must meet one of the following criteria:

• Of childbearing potential but agree to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from the screening until study completion)

• Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)

• 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

• Willingness to adhere to the study requirements

Exclusion Criteria:

An individual is not eligible if any of the following exclusion criteria are present:

• Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are lactating

• History of hypersensitivity to glucagon or any related products or severe hypersensitivity reactions (such as angioedema) to any drugs

• Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the investigator could interfere with the absorption, distribution, metabolism or excretion of drugs or could potentiate or predispose to undesired effects

• History of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma.

• History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the 1 month prior to enrolling in the study

• Use of daily systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs

• History of epilepsy or seizure disorder

• Regularly consumes 3 or more alcoholic beverages per day

• Use of an Investigational Product in another clinical trial within the past 30 days

• Donated 225 milliliters (mL) or more of blood in the previous 8 weeks before the first glucagon dosing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Davis Center for Diabetes	Aurora	Colorado	United States	80045
2	Yale University	New Haven	Connecticut	United States	06520
3	University of Florida	Gainesville	Florida	United States	32605
4	Riley Hospital for Children Indiana University Health	Indianapolis	Indiana	United States	46202
5	University of Minnesota	Minneapolis	Minnesota	United States	55454
6	UPA Buffalo	Buffalo	New York	United States	14222
7	Oregon Health and Science University	Portland	Oregon	United States	97239
8	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Eli Lilly and Company
• T1D Exchange Clinic Network Coordinating Center
• 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

• Rickels MR, Ruedy KJ, Foster NC, Piché CA, Dulude H, Sherr JL, Tamborlane WV, Bethin KE, DiMeglio LA, Wadwa RP, Ahmann AJ, Haller MJ, Nathan BM, Marcovina SM, Rampakakis E, Meng L, Beck RW; T1D Exchange Intranasal Glucagon Investigators. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care. 2016 Feb;39(2):264-70. doi: 10.2337/dc15-1498. Epub 2015 Dec 17.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01994746
• Other Study ID Numbers: 16422; INGluc001; I8R-MC-IGBC; AMG106
• First Posted: Nov 26, 2013
• Last Update Posted: Sep 23, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hypoglycemia; Diabetes Mellitus, Type 1; Glucagon; Glucagon-Like Peptide 1

Study Results

Participant Flow

Recruitment Details	77 Type 1 (T1D) and 6 Type 2 diabetes (T2D) participants were recruited. Results reported include T1D participants only since this was the pre-specified primary population.

Arm/Group Title	NG 1st/IM Glucagon 2nd	IM Glucagon 1st/NG 2nd
Arm/Group Description	At the first visit, 3 milligrams (mg) of nasal glucagon (NG). At the second visit, 1 mg of intramuscular (IM) glucagon.	At the first visit, 1 mg of IM glucagon. At the second visit, 3 mg of NG glucagon.
Period Title: First Visit
STARTED	39	38
Received At Least 1 Dose	39	38
COMPLETED	39	38
NOT COMPLETED	0	0
Period Title: First Visit
STARTED	38	38
Completed Both Dosing Visits	38	38
COMPLETED	38	38
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	At one visit, a nasal glucagon (NG) dose of 3 mg. At another visit, 1 mg intramuscular (IM) glucagon The order of the visits were randomized.
Overall Participants	77
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	77 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33 (12)
Sex: Female, Male (Count of Participants)
Female	45 58.4%
Male	32 41.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.3%
Not Hispanic or Latino	75 97.4%
Unknown or Not Reported	1 1.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 1.3%
White	74 96.1%
More than one race	0 0%
Unknown or Not Reported	2 2.6%
Region of Enrollment (Count of Participants)
United States	77 100%

Outcome Measures

1. Primary Outcome

Title	Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir
Description	Increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level defines treatment success. Due to the residual activity of circulating insulin, glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes following glucagon administration.
Time Frame	Within 30 minutes after receiving glucagon at both dosing visits (glucose was measured at pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration)

Outcome Measure Data

Analysis Population Description

All enrolled participants who completed both eligible Study/Dosing Visits.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	75	75
Number [percentage of participants]	98.7 128.2%	100 NaN

2. Secondary Outcome

Title	Nasal and Non-nasal Effects/Symptoms
Description	Symptoms of runny nose, nasal congestion and/or itching, sneezing, watery and/or itchy eyes, redness of eyes, and itching of ears and/or throat were assessed. This was done via the "Nasal Non-nasal Score Questionnaire". Each of the 9 symptoms is assigned an integer value from 0 to 3; higher values indicate more severe symptoms (a score of 0 indicates no symptoms). The reported results indicate the cohort median out of a possible maximum value of 27 (summing all 9 questions for each subject and reporting the median/IQR across participants).
Time Frame	Pre-dose; 15, 30, 60, and 90 post glucagon administration

Outcome Measure Data

Analysis Population Description

All enrolled T1D participants that completed the required dosing visits. Study dosing visits occur on Day 0 and then again after the washout period between Day 7 to Day 28.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	77	76
Pre-dose	0.00	0.00
15 minutes post glucagon administration	2.00	0.00
30 minutes post glucagon administration	1.00	0.00
60 minutes post glucagon administration	1.00	0.00
90 minutes post glucagon administration	1.00	0.00

3. Secondary Outcome

Title	Recovery From Symptoms of Hypoglycemia
Description	Recovery from hypoglycemia symptoms were assessed using the Edinburgh Hypoglycemia Scale. The Edinburgh Hypoglycemia Symptom Scale measures the intensity of 15 commonly experienced hypoglycemic symptoms on a 7-point Likert scale (1 = not present, 7 = very intense). The higher the score, the more intense the hypoglycemia symptoms. The sum of each symptom score would yield a range of 15 to 105 (i.e., 15 x 7 =105). The total score was calculated as the sum of each symptom score minus 15, and summarized at each time point by treatment group.
Time Frame	Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon

Outcome Measure Data

Analysis Population Description

All enrolled participants who completed at least one post administration survey.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	77	76
Pre-dose	8.0 (7.7)	7.8 (7.1)
15 minutes post glucagon administration	8.8 (8.3)	5.3 (5.2)
30 minutes post glucagon administration	4.9 (4.7)	3.5 (3.9)
45 minutes post glucagon administration	3.8 (3.1)	3.0 (3.0)
60 minutes post glucagon administration	3.9 (3.1)	3.1 (2.9)

4. Secondary Outcome

Title	Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir
Description	The mean time from glucagon administration to blood glucose >/=70 mg/dL or an increase ≥20 mg/dL in blood glucose from nadir.
Time Frame	Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration

Outcome Measure Data

Analysis Population Description

All enrolled participants that completed the required dosing visits with eligible glucose and glucagon levels. Study dosing visits occur on Day 0 and then again after the washout period between Day 7 to Day 28.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	75	75
Number [minutes]	16.2	12.2

5. Secondary Outcome

Title	Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon
Time Frame	Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

Outcome Measure Data

Analysis Population Description

All enrolled participants that completed the required dosing visits with available pharmacokinetics (PK) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	75	75
Mean (Standard Deviation) [hour*picograms per milliliter (hr*pg/mL)]	1882.48 (1216.27)	2521.87 (971.07)

6. Secondary Outcome

Title	Maximum Change From Baseline Concentration (Cmax) of Glucagon
Time Frame	Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

Outcome Measure Data

Analysis Population Description

All enrolled participants that completed the required dosing visits with available pharmacokinetics (PK) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	75	75
Mean (Standard Deviation) [picograms per milliliter (pg/mL)]	3025.37 (1981.62)	3553.43 (1746.66)

7. Secondary Outcome

Title	Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon
Time Frame	Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

Outcome Measure Data

Analysis Population Description

All enrolled participants that completed the required dosing visits with available pharmacokinetics (PK) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	75	75
Median (Full Range) [hours]	0.33	0.25

8. Secondary Outcome

Title	Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes
Time Frame	Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

Outcome Measure Data

Analysis Population Description

All enrolled participants that completed the required dosing visits with available pharmacodynamics (PD) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	75	75
Mean (Standard Deviation) [hr*mg/dL]	106.39 (42.60)	124.47 (38.95)

9. Secondary Outcome

Title	Maximum Change From Baseline Concentration (Cmax) of Glucose
Time Frame	Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

Outcome Measure Data

Analysis Population Description

All enrolled participants that completed the required dosing visits with available pharmacodynamics (PD) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	75	75
Mean (Standard Deviation) [milligrams per deciliter (mg/dL)]	114.80 (47.45)	130.72 (44.15)

10. Secondary Outcome

Title	Time to Maximum Change From Baseline Concentration (Tmax) of Glucose
Time Frame	Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

Outcome Measure Data

Analysis Population Description

All enrolled participants that completed the required dosing visits with available pharmacodynamics (PD) data. Study dosing visits occurred on Day 0 and then again after the washout period between Day 7 to Day 28.

Arm/Group Title	Nasal Glucagon (NG)	Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.	At a separate visit, 1 mg of IM glucagon.
Measure Participants	75	75
Median (Full Range) [hours]	1.5	1.5

Adverse Events

Time Frame	Through study completion, up to 48 days
Adverse Event Reporting Description	Included all participants received at least one dose of glucagon.
Arm/Group Title	Nasal Glucagon (NG)		Intramuscular (IM) Glucagon
Arm/Group Description	At one visit, 3 mg of NG.		At a separate visit, 1 mg of IM glucagon.
All Cause Mortality
	Nasal Glucagon (NG)		Intramuscular (IM) Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nasal Glucagon (NG)		Intramuscular (IM) Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/77 (0%)		0/77 (0%)
Other (Not Including Serious) Adverse Events
	Nasal Glucagon (NG)		Intramuscular (IM) Glucagon
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/77 (57.1%)		35/76 (46.1%)
Ear and labyrinth disorders
Ear pain	2/77 (2.6%)		1/76 (1.3%)
Endocrine disorders
Hyperglycemia	1/77 (1.3%)		0/76 (0%)
Eye disorders
Eye pain	1/77 (1.3%)		0/76 (0%)
Eye pruritus	2/77 (2.6%)		1/76 (1.3%)
Lacrimation increased	7/77 (9.1%)		1/76 (1.3%)
Ocular hyperemia	1/77 (1.3%)		0/76 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/77 (1.3%)		1/76 (1.3%)
Nausea	17/77 (22.1%)		21/76 (27.6%)
Vomiting	13/77 (16.9%)		9/76 (11.8%)
General disorders
Facial pain	2/77 (2.6%)		0/76 (0%)
Fatigue	6/77 (7.8%)		5/76 (6.6%)
Lethargy	0/77 (0%)		1/76 (1.3%)
Somnolence	2/77 (2.6%)		0/76 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	2/77 (2.6%)		0/76 (0%)
Headache	18/77 (23.4%)		7/76 (9.2%)
Neck pain	1/77 (1.3%)		0/76 (0%)
Nervous system disorders
Hot flush	0/77 (0%)		1/76 (1.3%)
Hyperhidrosis	1/77 (1.3%)		1/76 (1.3%)
Psychiatric disorders
Confusional state	1/77 (1.3%)		0/76 (0%)
Disturbance in attention	1/77 (1.3%)		0/76 (0%)
Anxiety	1/77 (1.3%)		0/76 (0%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	6/77 (7.8%)		1/76 (1.3%)
Nasal discomfort	8/77 (10.4%)		0/76 (0%)
Nasal edema	1/77 (1.3%)		0/76 (0%)
Rhinorrhoea	2/77 (2.6%)		1/76 (1.3%)
Cough	1/77 (1.3%)		0/76 (0%)
Upper airway cough syndrome	1/77 (1.3%)		0/76 (0%)
Skin and subcutaneous tissue disorders
Pruritus	2/77 (2.6%)		1/76 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.