Trial Outcomes & Findings for Clinical Usability of Intranasal Glucagon in Treatment of Hypoglycemia (NCT NCT02171130)

Last Updated: 2019-10-15

Results Overview

Responses to questions completed by the caregiver were used to assess this outcome. An episode of severe hypoglycemia was defined as an episode wherein the person with diabetes is clinically incapacitated to the point where the person requires third-party assistance to treat the hypoglycemia. An episode of moderate hypoglycemia episode was defined as an episode wherein the person with diabetes was showing signs of neuroglycopenia and had a glucometer reading of approximately 60 milligrams per deciliter (mg/dL) (3.3 millimoles per liter \[mmol/L\]) or less based on a blood sample taken at or near the time of treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

129 participants

Primary outcome timeframe

Within 30 minutes after each drug administration for an episode of hypoglycemia

Results posted on

2019-10-15

Participant Flow

Participants and their principal caregiver(s) were trained in the use of nasal glucagon.

Participant milestones

Participant milestones
Measure	Nasal Glucagon (NG) Nasal Glucagon powder (3 milligram \[mg\])
Overall Study STARTED	129
Overall Study Received at Least One Dose of Study Drug	87
Overall Study Experienced Hypoglycemic Event	87
Overall Study COMPLETED	101
Overall Study NOT COMPLETED	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Nasal Glucagon (NG) Nasal Glucagon powder (3 milligram \[mg\])
Overall Study Death	1
Overall Study Discontinued; Clinical Material Issue	16
Overall Study Discontinued; Site Termination	5
Overall Study Withdrawal by Subject	3
Overall Study Physician Decision	1
Overall Study Lost to Follow-up	1
Overall Study Met Exclusion Criteria	1

Baseline Characteristics

Clinical Usability of Intranasal Glucagon in Treatment of Hypoglycemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nasal Glucagon n=129 Participants Nasal Glucagon powder (3mg)
Age, Continuous	46.6 years STANDARD_DEVIATION 14.43 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants
Sex: Female, Male Male	73 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 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	5 Participants n=5 Participants
Race (NIH/OMB) White	123 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 Canada	81 Participants n=5 Participants
Region of Enrollment United States	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 30 minutes after each drug administration for an episode of hypoglycemia

Population: Enrolled participants received at least 1 dose of the study drug with evaluable hypoglycemic event. Events requiring additional medical assistance or rescue therapy within 30 minutes of study drug administration and participants from a Good Clinical Practice (GCP) non-compliant site were excluded.

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=69 Participants Nasal Glucagon powder (3mg)
Percentage of Participants Awakening or Returning to a Normal Status Within 30 Minutes Following Studied Drug of Administration	95.7 percentage of participants

SECONDARY outcome

Timeframe: After each drug administration for an episode of hypoglycemia

Population: Eligible enrolled participants who experienced at least 1 hypoglycemic event and received at least 1 dose of study drug. Participants from the GCP non-compliant site and participants who were impacted by a clinical material issue which might have led to under-dose, were considered ineligible thus excluded from this population.

Measurement for Degree of difficulty: opening the kit, Degree of difficulty: understanding the instructions on how to use the kit, Degree of difficulty: administering the medication into the nostril, Degree of satisfaction is 1 (Very Difficult) to 7 (Very Easy). Measurement for Dry Mist Nasal Glucagon will be easy to teach other caregivers, Nasal formulation of glucagon is less intimidating for caregivers, Nasal Glucagon is easy to carry and would be willing to carry it, nasal delivery of glucagon is preferable. Level of agreement 1 (Strongly Disagree) to 7 (Strongly Agree).

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=179 Total Number of Events Nasal Glucagon powder (3mg)
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: opening the kit (Very Difficult)	2 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: opening the kit (Average)	4 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: opening the kit (Relatively Easy)	4 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: opening the kit (Easy)	26 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: opening the kit (Very Easy)	143 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: instructions (Very Difficult)	2 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: instructions (Average)	4 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: instructions (Relatively Easy)	10 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: instructions (Easy)	36 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: instructions (Very Easy)	127 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: administering (Very Difficult)	4 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: administering (Relatively Difficult)	7 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: administering (Average)	8 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: administering (Relatively Easy)	16 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: administering (Easy)	42 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Difficulty: administering (Very Easy)	102 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Time to administer (<30 seconds)	126 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Time to administer (30-<60 seconds)	40 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Time to administer (1-<2 minutes)	9 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Time to administer (2-<5 minutes)	4 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Degree of satisfaction (Relatively Difficult)	3 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Degree of satisfaction (Average)	7 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Degree of satisfaction (Relatively Easy)	21 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Degree of satisfaction (Easy)	48 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Degree of satisfaction (Very Easy)	100 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Compare to Injectable (Not Applicable)	108 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Compare to Injectable (Much Easier)	47 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Compare to Injectable (Easier)	4 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Compare to Injectable (Missing)	20 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Ease to teach other (Neither Agree nor Disagree)	2 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Ease to teach other (Somewhat Agree)	3 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Ease to teach other (Mostly Agree)	47 Total Number of Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon as Determined by Completion of Questionnaires by the Caregiver Ease to teach other (Strongly Agree)	127 Total Number of Events

SECONDARY outcome

Timeframe: Within 2 hours of full recovery from a hypoglycemic event

Population: Eligible enrolled participants who experienced at least 1 hypoglycemic event and received at least 1 dose of study drug.

Adverse events solicited through the Nasal Score Questionnaire included: runny nose, nasal congestion (nostrils plugged), nasal itching, sneezing, watery eyes, itchy eyes, redness of eyes, itching of ears, itching of throat, and other. A summary of other nonserious AEs, and all Serious Adverse Events (SAEs), regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=87 Participants Nasal Glucagon powder (3mg)
Percentage of Participants With Adverse Events (AEs) Reported Through the Nasal Score Questionnaire	82.8 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (just prior to dosing or right after study drug administration) , 15, 30 and 45 minutes after drug administration for an episode of hypoglycemia

The participants' blood glucose level was measured by the caregiver using a glucometer at baseline (just prior to dosing and right after the study drug administration), 15, 30 and 45 minutes after nasal glucagon administration.

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=157 Total Number of Hypoglycemic Events Nasal Glucagon powder (3mg)
Blood Glucose Levels Over Time Baseline	47.9 milligram/deciliter (mg/dL) Standard Deviation 10.47
Blood Glucose Levels Over Time 15 minutes drug administration	84.4 milligram/deciliter (mg/dL) Standard Deviation 24.68
Blood Glucose Levels Over Time 30 minutes drug administration	112.8 milligram/deciliter (mg/dL) Standard Deviation 34.33
Blood Glucose Levels Over Time 45 minutes drug administration	123.1 milligram/deciliter (mg/dL) Standard Deviation 38.82

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and End of Study (6 months)

Population: Enrolled participants who had antibody sample at both baseline and post-baseline.

Treatment-Emergent ADA includes treatment-induced ADA ('Not Detected' ADA at baseline and at least one post-baseline 'Detected' ADA sample with a corresponding titer of (1:20) and treatment-boosted ADA (with 'Detected' ADA at baseline and at least one post-baseline 'Detected' ADA sample with a corresponding titer that is at least 4-fold higher than the baseline titer.

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=43 Participants Nasal Glucagon powder (3mg)
Number of Participants With Treatment-Emergent Glucagon Anti-Drug Antibodies (ADA)	0 percentage of participants

Adverse Events

Nasal Glucagon

Serious events: 1 serious events

Other events: 74 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Nasal Glucagon n=87 participants at risk Nasal Glucagon powder (3mg)
General disorders Death	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.

Other adverse events

Other adverse events
Measure	Nasal Glucagon n=87 participants at risk Nasal Glucagon powder (3mg)
Ear and labyrinth disorders Ear pain	5.7% 5/87 • Number of events 6 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Eye disorders Eye inflammation	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Eye disorders Eye pain	2.3% 2/87 • Number of events 3 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Eye disorders Hypoaesthesia eye	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Eye disorders Lacrimation increased	9.2% 8/87 • Number of events 10 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
General disorders Asthenia	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
General disorders Facial pain	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
General disorders Feeling abnormal	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
General disorders Pain	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
General disorders Product taste abnormal	3.4% 3/87 • Number of events 3 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Musculoskeletal and connective tissue disorders Muscle tightness	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Nervous system disorders Burning sensation	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Nervous system disorders Head discomfort	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Nervous system disorders Sinus headache	2.3% 2/87 • Number of events 2 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Nervous system disorders Somnolence	1.1% 1/87 • Number of events 2 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Respiratory, thoracic and mediastinal disorders Choking	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Respiratory, thoracic and mediastinal disorders Cough	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.3% 2/87 • Number of events 2 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	3.4% 3/87 • Number of events 5 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	3.4% 3/87 • Number of events 3 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.3% 2/87 • Number of events 2 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Respiratory, thoracic and mediastinal disorders Sneezing	2.3% 2/87 • Number of events 2 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Skin and subcutaneous tissue disorders Erythema	1.1% 1/87 • Number of events 1 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Gastrointestinal disorders Nausea	23.0% 20/87 • Number of events 29 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Gastrointestinal disorders Vomiting	9.2% 8/87 • Number of events 16 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Respiratory, thoracic and mediastinal disorders Nasal Irritation	77.0% 67/87 • Number of events 117 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.
Nervous system disorders Headache	51.7% 45/87 • Number of events 72 • After study drug administration, up to 6 months. Adverse events were collected systematically using the Hypoglycemia Questionnaire. Analysis population included participants with at least one exposure to study drug after hypoglycemic event.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60