Trial Outcomes & Findings for Clinical Usability of Nasal Glucagon in Treatment of Hypoglycemia in Children and Adolescents (NCT NCT02402933)

Last Updated: 2019-09-23

Results Overview

Responses to questions completed by the caregiver are used to assess this outcome. An episode of severe hypoglycemia is generally defined as an event associated with severe neuroglycopenia usually resulting in coma or seizure and requiring parenteral therapy (glucagon or intravenous glucose) administered by a third party. In this study moderate hypoglycemia is defined as an episode wherein the child/adolescent with diabetes has symptoms and/or signs of neuroglycopenia and has a blood glucose ≤3.9 millimoles per liter (mmol/L) (70 milligram per deciliter \[mg/dL\]) based on a blood sample taken at or close to the time of treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

26 participants

Primary outcome timeframe

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

Results posted on

2019-09-23

Participant Flow

Participants and their principal caregiver(s) (such as parents, family member, roommate, teacher, and coach) were trained in the use of nasal glucagon.

Participant milestones

Participant milestones
Measure	Nasal Glucagon (NG) A single dose of 3 mg glucagon nasal powder administered using a nasal powder delivery device for the treatment of moderate or severe hypoglycemic events; a maximum of 4 events per participant during the study.
Overall Study STARTED	26
Overall Study Received at Least One Dose of Study Drug	22
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Nasal Glucagon (NG) A single dose of 3 mg glucagon nasal powder administered using a nasal powder delivery device for the treatment of moderate or severe hypoglycemic events; a maximum of 4 events per participant during the study.
Overall Study Withdrawal by Subject	4
Overall Study Discontinued; Site Termination	10

Baseline Characteristics

Clinical Usability of Nasal Glucagon in Treatment of Hypoglycemia in Children and Adolescents

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nasal Glucagon (NG) n=26 Participants Nasal glucagon 3 milligram (mg)
Age, Continuous	11.7 years STANDARD_DEVIATION 3.73 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	11 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	1 Participants n=5 Participants
Race (NIH/OMB) White	25 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 United States	26 Participants n=5 Participants

PRIMARY outcome

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

Population: Participants who received at least 1 dose of NG with evaluable treatment response. Events for which participants required external professional medical assistance or used injected glucagon or oral carbohydrates within 30 minutes and before responding were non-evaluable. The good clinical practice (GCP) non-compliant site were also excluded.

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=14 Participants Nasal glucagon (NG) 3 mg
Number of Participants Awakening or Returning to a Normal Status Within 30 Minutes Following Studied Drug of Administration	14 participants

SECONDARY outcome

Timeframe: After each drug administration for an episode of hypoglycemia

Population: Participants who received at least 1 dose of NG and experienced at least 1 hypoglycemic event. Participants from the GCP non-compliant site were excluded. Proportions and n are based on the total number of hypoglycemic events (N=33) of 14 participants; except "Compare to Injectable" is based on 8 events.

Assess ease-of-use of intranasal administered glucagon in the hands of caregivers of participants who may be called upon to treat episodes of hypoglycemia. 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, Dry Mist Nasal Glucagon is easy to carry and would be willing to carry it, Intranasal delivery of glucagon is preferable: level of agreement 1 (Strongly Disagree) to 7 (Strongly Agree).

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=33 Hypoglycemic Events Nasal glucagon (NG) 3 mg
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: opening the kit (Easy)	6 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: opening the kit (Very Easy)	27 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: instructions (Average)	4 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: instructions (Relatively Easy)	1 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: instructions (Easy)	6 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: instructions (Very Easy)	22 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: administering (Average)	2 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: administering (Easy)	11 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Difficulty: administering (Very Easy)	20 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Time to administer (<30 seconds)	20 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Time to administer (30-<60 seconds)	9 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Time to administer (1-<2 minutes)	4 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Degree of satisfaction (Average)	2 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Degree of satisfaction (Relatively Easy)	1 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Degree of satisfaction (Easy)	8 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Degree of satisfaction (Very Easy)	22 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Compare to Injectable (Not Applicable)	25 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Compare to Injectable (Much Easier)	2 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Compare to Injectable (Easier)	2 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Compare to Injectable (About the Same)	4 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Ease to teach other (Easy)	4 Hypoglycemic Events
Assessment of Ease-of-use of Dry-Mist Nasal Glucagon by Completion of Questionnaire by the Caregiver Ease to teach other (Very Easy)	29 Hypoglycemic Events

SECONDARY outcome

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

Population: Participants who received at least 1 dose of NG and experienced at least 1 hypoglycemic event.Participants from the GCP non-compliant site were considered ineligible and thus excluded from this population.

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 non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=14 Participants Nasal glucagon (NG) 3 mg
Percentage of Participants With Adverse Events Through the Nasal Score Questionnaire	100 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

Population: Participants received at least 1 dose of the NG and experienced at least 1 hypoglycemic event. Participants from the GCP non-compliant site were considered ineligible and thus excluded from this population.

Glucometer-based measurements of blood glucose after the studied drug administration. The participants' change in blood glucose level from baseline (just prior to dosing or right after the study drug administration) was measured by the caregiver using a glucometer at 15, 30 and 45 minutes after NG administration. The change in glucose was calculated from each time point (15, 30 and 45 minutes) minus the baseline.

Outcome measures

Outcome measures
Measure	Nasal Glucagon n=14 Participants Nasal glucagon (NG) 3 mg
Change in Blood Glucose Level Over Time 15 minutes drug administration	58.2 milligram/deciliter (mg/dL) Standard Deviation 21.16
Change in Blood Glucose Level Over Time 30 minutes drug administration	106.8 milligram/deciliter (mg/dL) Standard Deviation 39.57
Change in Blood Glucose Level Over Time 45 minutes drug administration	124.1 milligram/deciliter (mg/dL) Standard Deviation 49.09

Adverse Events

Nasal Glucagon

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Nasal Glucagon n=22 participants at risk 3 mg glucagon powder
Gastrointestinal disorders Abdominal Pain Upper	9.1% 2/22 • Number of events 2 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Nervous system disorders Dizziness	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Injury, poisoning and procedural complications Face Injury	4.5% 1/22 • Number of events 4 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
General disorders Fatigue	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
General disorders Headache	63.6% 14/22 • Number of events 26 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Investigations Incomplete Dose Administered	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Respiratory, thoracic and mediastinal disorders Nasal Discomfort	86.4% 19/22 • Number of events 41 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Gastrointestinal disorders Nausea	27.3% 6/22 • Number of events 10 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Respiratory, thoracic and mediastinal disorders Paranasal Sinus Hypersecretion	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
General disorders Product Taste Abnormal	4.5% 1/22 • Number of events 2 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	9.1% 2/22 • Number of events 2 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Nervous system disorders Somnolence	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Nervous system disorders Tremor	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Gastrointestinal disorders Vomiting	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Eye disorders Watery Eyes	81.8% 18/22 • Number of events 37 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.
Respiratory, thoracic and mediastinal disorders Sneezing	4.5% 1/22 • Number of events 1 All participants who received at least one dose of NG, including GCP non-compliance site. Adverse events were collected systematically using the Hypoglycemia Questionnaire.

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: LTE60