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Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT01997411
Recruitment Status : Completed
First Posted : November 28, 2013
Results First Posted : March 6, 2017
Last Update Posted : August 29, 2018
Sponsor:
Collaborators:
Jaeb Center for Health Research
Locemia Solutions ULC
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The purpose of this study was to assess how glucagon administered nasally, using a nasal dosing delivery device, works in children and adolescents compared with commercially-available glucagon given by injection. In addition, the safety and tolerability of glucagon given nasally was evaluated.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Nasal Glucagon Drug: Intramuscular Glucagon Phase 2 Phase 3

Detailed Description:

This study was conducted to permit determination of appropriate dose level(s) for pediatric use based on the safety observations and results of glucagon and glucose assays.

Each participant 12 to less than 17 years of age underwent two visits in random order and received glucagon nasal powder once and commercially available glucagon (GlucaGen, Novo Nordisk) by intramuscular (IM) injection once. Participants 4 to less than 12 years were randomly assigned to have either 1 visit with commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection OR to have 2 visits with a 2.0 milligram (mg) dose of glucagon nasal powder administered during one visit and a 3.0 mg dose of glucagon nasal powder administered during the other visit. For those randomized to complete two research dosing visits, the dose of glucagon nasal powder given during each visit was masked to the participant and study personnel.

Glucagon was administered after glucose was lowered to <80 mg/dL using insulin if necessary on the dosing day. Participants were treated with either glucagon given nasally (either 2.0 mg or 3.0 mg for participants 4 to less than 12 years of age or 3.0 mg for those 12 to less than 17 years of age) or by intramuscular (IM) injection (1 mg for those 55 pounds [lbs] or more and 0.5 mg for those weighing less than 55 lbs) in the quadriceps muscle of the leg.

Blood glucose levels and adverse events were carefully monitored for 90 minutes post-dosing. After a wash-out period of 7 days or more, participants 12 to less than 17 years of age returned to the clinic and the procedure was repeated with each participant crossed over to the other treatment. Participants 4 to less than 12 years assigned to have 2 dosing visits returned to clinic for repeated procedures and received alternate dose of nasal glucagon (NG). Participants 4 to less than 12 years assigned to a single dosing visit did not return for a second dosing visit.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: IM and NG arms are open labeled. NG cohorts, 2mg and 3mg, are quadruple blinded.
Primary Purpose: Treatment
Official Title: Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes
Study Start Date : November 2013
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
Drug Information available for: Glucagon

Arm Intervention/treatment
Experimental: Nasal Glucagon (NG)
Nasal glucagon (NG) doses of 2.0 mg and 3.0 mg for participants 4 to less than 12 years of age and 3.0 mg for those 12 to less than 17 years of age were administered in a nostril with a prefilled delivery device that delivered a single dose upon activation.
Drug: Nasal Glucagon
Other Names:
  • AMG504-1
  • LY900018

Active Comparator: Intramuscular (IM) Glucagon
Participants who weighed at least 25 kilograms (kg)/55 pounds (lbs) were dosed 1 mg of IM glucagon; participants who weighed less than 25 kg/55 lbs, IM glucagon dosed with 0.5 mg
Drug: Intramuscular Glucagon
Other Name: GlucaGen HypoKit




Primary Outcome Measures :
  1. Maximum Change From Baseline Concentration (Cmax) of Glucagon [ Time Frame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration ]
  2. Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon [ Time Frame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration ]
  3. Area Under the Curve (AUC0-1.5) of Baseline Adjusted Glucagon [ Time Frame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration ]
  4. Maximum Concentration (Cmax) of Baseline-Adjusted Glucose [ Time Frame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration ]
  5. Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose [ Time Frame: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration ]
  6. 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, 30, 40, 60 and 90 minutes following glucagon administration ]

Secondary Outcome Measures :
  1. Nasal and Non-nasal Effects/Symptoms [ Time Frame: Pre-dose;15, 30, 60 and 90 minutes following 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 prior to administering glucagon and at 15, 30, 60 and 90 minutes following administration of glucagon. 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 participant and reporting the median/IQR across participants).

  2. Number of Participants Achieving at Least a 25 mg/dL Rise in Blood Glucose Above Nadir Level Within 30 Minutes [ Time Frame: Pre-dose; 5, 10, 15, 20, and 30 minutes following glucagon administration ]
  3. Time to Achieving ≥25 mg/dL Rise in Plasma Glucose Above Nadir Level Within 30 Minutes [ Time Frame: Pre-dose; 5, 10, 15, 20, and 30 minutes following glucagon administration ]
    Time (in minutes) when all participants experienced a rise in glucose >=25mg/dL. This is an absolute number and is not a calculated statistic. There is no distribution per cohort.


Other Outcome Measures:
  1. Percentage of Participants With >= 25 mg/dL Rise in Plasma Glucose Within 30 Minutes [ Time Frame: Pre-dose; 5, 10,15, 20, and 30 minutes following glucagon administration ]


Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible, the following inclusion criteria were met:

  • History of type 1 diabetes and receiving daily insulin therapy from the time of diagnosis for at least 12 months
  • At least 4 years of age and less than 17 years
  • Females must have met one of the following criteria:

    • Of childbearing potential but agreed to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from screening until study completion)
    • Of non-childbearing potential, defined as a female who had a hysterectomy or tubal ligation, was clinically considered infertile or had not yet reached menarche
  • In good general health with no conditions that could have influenced the outcome of the trial, and in the judgment of the Investigator was 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 was not eligible if any of the following exclusion criteria were present:

  • Females who were pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or were 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 have interfered 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
  • Use of an Investigational Product in another clinical trial within the past 30 days
  • Blood donation in 3 months prior to first glucagon dosing

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01997411


Locations
United States, Colorado
Barbara Davis Center for Diabetes
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Florida
University of Florida
Gainesville, Florida, United States, 32605
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
United States, Indiana
Riley Hospital for Children Indiana University Health
Indianapolis, Indiana, United States, 46202
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55454
United States, New York
UPA Buffalo
Buffalo, New York, United States, 14222
Sponsors and Collaborators
Eli Lilly and Company
Jaeb Center for Health Research
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01997411     History of Changes
Other Study ID Numbers: 16418
I8R-MC-IGBB ( Other Identifier: Eli Lilly and Company )
INGluc002 ( Other Identifier: Jaeb Center for Health Research )
AMG103 ( Other Identifier: Locemia )
First Posted: November 28, 2013    Key Record Dates
Results First Posted: March 6, 2017
Last Update Posted: August 29, 2018
Last Verified: August 2018

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Glucagon
Glucagon-Like Peptide 1
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins