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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by T1D Exchange Clinic Network Coordinating Center
Sponsor:
Collaborator:
Locemia Solutions ULC
Information provided by (Responsible Party):
T1D Exchange Clinic Network Coordinating Center
ClinicalTrials.gov Identifier:
NCT01997411
First received: November 22, 2013
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to assess how glucagon administered as a puff into the nose (AMG504-1) works in children and adolescents compared with commercially-available glucagon given by injection. In addition, the safety and tolerability of glucagon given as a puff into the nose will be evaluated.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: Intranasal Glucagon
Drug: Glucagon
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by T1D Exchange Clinic Network Coordinating Center:

Primary Outcome Measures:
  • Area under the curve from time zero to the last quantifiable concentration (AUC0-t) of glucagon [ Time Frame: 0 to 90 minutes following administration of glucagon ] [ Designated as safety issue: No ]
  • Maximum observed concentration (Cmax) of glucagon [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: No ]
  • Time to maximum concentration (tmax) of glucagon [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Nasal and non-nasal effects/symptoms [ Time Frame: 15 to 90 minutes post glucagon administration ] [ Designated as safety issue: Yes ]
    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 will be assessed at 15, 30, 60 and 90 minutes following administration of glucagon.

  • Maximum concentration (Cmax) of glucose [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: No ]
  • Time to maximum concentration (Tmax) of glucose [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: No ]
  • Area under the effect concentration time curve (AUEC0-1.5) of glucose from time zero up to 90 minutes [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: No ]
  • The proportion and 99% confidence interval of the proportion of participants achieving at least a 25 mg/dl rise in blood glucose above basal level [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: No ]
  • Time to achieving ≥25 mg/dl rise in plasma glucose above basal level [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: November 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intranasal glucagon
Glucagon doses of 2.0 mg and 3.0 mg for participants 4.0 to less than 12.0 years of age and 3.0 mg for those 12.0 to less than 17.0 years of age (equivalent to 20 mg or 30 mg of AMG 504-1 dry powder, respectively) will be administered in a nostril with a prefilled delivery device that delivers a single dose upon activation.
Drug: Intranasal Glucagon
Other Name: AMG504-1
Active Comparator: Glucagon
For participants who weigh at least 25 kg (55) lbs, the dose will consist of 1 mg of recombinant human glucagon United States Pharmacopeia (USP) which will be constituted in the commercially provided prefilled disposable syringe containing 1 mL of diluting solution. For participants who weigh less than 25 kg, the dose will be 0.5 mg constituted in 1 mL of diluting solution.
Drug: Glucagon
Other Name: GlucaGen HypoKit

Detailed Description:

Glucagon, the treatment of choice for severe hypoglycemia outside of the hospital setting, is currently available only as a powder that must be mixed with a diluent immediately prior to administration by injection. Although this is a very simple procedure for insulin-using individuals, subjects experiencing severe hypoglycemia cannot inject themselves with glucagon because of the disabling effects of severe neuroglycopenia. For any non-medical person who is confronted with an emergency situation in which a patient with diabetes is in a hypoglycemic coma or suffering hypoglycemia-related convulsions, reconstitution and injection of the current injectable glucagon is a complex and daunting procedure.

When used at the recommended dose of 1 mg by injection, glucagon often causes a substantial, although transient, hyperglycemia that is often accompanied by nausea and vomiting. The data generated to date with AMG504-1 suggest the resulting glucagon pharmacokinetics (PK), although less than that observed with injected glucagon, results in a therapeutic blood glucose increment with a very low incidence of gastrointestinal adverse effects.

Caregivers of children and adolescents with type 1 diabetes are called upon to treat episodes of severe hypoglycemia and may want to use AMG504-1. This study is being 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 12.0 to less than 17.0 years of age will undergo two visits in random order and receive AMG504-1 during one visit and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other visit. Participants 4.0 to less than 12.0 years are 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 mg dose of AMG504-1 administered during one visit and a 3.0 mg dose of AMG504-1 administered during the other visit. For those randomized to complete two research dosing visits, the dose of intranasal glucagon given during each visit will be masked to the participant and study personnel.

Each dosing visit consists of reducing the plasma glucose level to about 80 mg/dL by increasing the basal insulin infusion rate on the insulin pump or by an intravenous (IV) infusion of regular insulin diluted in normal saline. The insulin infusion will be stopped once the plasma glucose is <80 mg/dL. Five minutes after stopping the insulin infusion, participants will be treated with either glucagon given intranasally (either 2.0 mg or 3.0 mg for participants 4.0 to less than 12.0 years of age or 3.0 mg for those 12.0 to less than 17.0 years of age) or by intramuscular (IM) injection (1 mg constituted in 1 mL of diluting solution for those 55 lbs or more and 0.5 mg constituted in 1 mL of diluting solution for those who weigh less than 55 lbs) in the quadriceps muscle of the leg.

Blood glucose levels and adverse events will be carefully monitored for 90 minutes post-dosing. After a wash-out period of 7 days or more, participants 12.0 to less than 17.0 years of age will return to the clinic and the procedure repeated with each participant crossed over to the other treatment. Participants 4.0 to less than 12.0 years assigned to have 2 dosing visits will also return to clinic and repeat the procedure with a different dose of intranasal glucagon given. Participants 4.0 to less than 12.0 years assigned to a single dosing visit do not return for a second dosing visit.

  Eligibility

Ages Eligible for Study:   4 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  1. History of type 1 diabetes and receiving daily insulin therapy from the time of diagnosis for at least 12 months.
  2. At least 4.0 years of age and less than 17.0 years.
  3. Weighs at least:

    • 13 kg (28.6 lbs) for centers that are allowed to reinfuse blood and Institutional Review Board (IRB) guidelines allow for 3.5 ml/kg of blood to be collected
    • 15.1 kg (33.2 lbs) for centers that are allowed to reinfuse blood and IRB guidelines allow for 3.0 ml/kg of blood to be collected
    • 19 kg (41.8 lbs) for centers that are not allowed to reinfuse blood and IRB guidelines allow for 3.5 ml/kg of blood to be collected
    • 22.1 kg (48.6 lbs) for centers that are not allowed to reinfuse blood and IRB guidelines allow for 3.0 ml/kg of blood to be collected
  4. Females must meet one of the following criteria:

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

      or

    2. Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or has not yet reached menarche.
  5. 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.
  6. Willingness to adhere to the protocol requirements

Exclusion Criteria:

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

  1. 1. Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are lactating.
  2. History of hypersensitivity to glucagon or any related products or severe hypersensitivity reactions (such as angioedema) to any drugs.
  3. 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.
  4. History of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma.
  5. 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.
  6. Use of daily systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs.
  7. History of epilepsy or seizure disorder.
  8. Use of an Investigational Product in another clinical trial within the past 30 days
  9. Blood donation in 3 months prior to first glucagon dosing visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01997411

Contacts
Contact: Katrina J Ruedy, MSPH 813-975-8690 kruedy@Jaeb.org
Contact: Beth A Stevens, BA 813-975-8690 bstevens@jaeb.org

Locations
United States, Colorado
Barbara Davis Center for Diabetes Recruiting
Aurora, Colorado, United States, 80045
Contact: Leena Nguyen, MPH    303-724-5554    Nhung.Nguyen@ucdenver.edu   
Principal Investigator: R. Paul Wadwa, MD         
Sub-Investigator: David Maahs, MD         
Sub-Investigator: Georgeanna Klingensmith, MD         
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Lori Carria, MS    203-737-3595    lori.carria@yale.edu   
Principal Investigator: Jennifer Sherr, MD, PhD         
Sub-Investigator: William Tamborlane, MD         
Sub-Investigator: Eda Cengiz, MD         
Sub-Investigator: Camille Michaud, MD         
Sub-Investigator: Neha Patel, DO         
Sub-Investigator: Lital Reitblat, MD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32605
Contact: Miriam Cintron    352-273-5580    cintronm@ufl.edu   
Principal Investigator: Desmond Schatz, MD         
Sub-Investigator: Michael J Haller, MD         
Sub-Investigator: Janet Silverstein, MD         
Sub-Investigator: Henry Rohrs, MD         
Nemours Children's Clinic Recruiting
Jacksonville, Florida, United States, 32207
Contact: Kimberly Englert, BSN, RN    904-697-3056    Kenglert@nemours.org   
Sub-Investigator: Larry Fox, MD         
Sub-Investigator: Nelly Mauras, MD         
United States, Indiana
Riley Hospital for Children Indiana University Health Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Stephanie Woerner, MSN,FNPC,CDE    317-944-3889    sestein@iu.edu   
Principal Investigator: Linda DiMeglio, MD         
Sub-Investigator: Emily Sims, MD         
Sub-Investigator: Juan Sanchez, MD         
Sub-Investigator: Carmella Evans-Molina, MD         
Sub-Investigator: Marisa Fisher, MD         
United States, Massachusetts
University of Massachusettes Not yet recruiting
Worcester, Massachusetts, United States, 01655
Contact: Carol Ciccarello, RN, CDE    508-856-2828    Carol.Ciccarelli@umassmed.edu   
Principal Investigator: Leslie Soyka, MD         
Sub-Investigator: Mary Lee, MD         
Sub-Investigator: Penny Feldman, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55454
Contact: Janice Leschyshyn, RN, CCRP    612-626-8467    lesch004@umn.edu   
Principal Investigator: Brandon Nathan, MD         
Sub-Investigator: Antoinette Moran, MD         
Sub-Investigator: Melena Bellin, MD         
United States, New York
UPA Buffalo Not yet recruiting
Buffalo, New York, United States, 14222
Contact: Michelle Ecker, Rd, CDN, CDE    716-878-7609    mecker@upa.chob.edu   
Principal Investigator: Kathy Bethin, MD         
Sub-Investigator: Lucy Mastrandrea, MD         
Sub-Investigator: Indrajit Majumdar, MBBS         
Sponsors and Collaborators
T1D Exchange Clinic Network Coordinating Center
Locemia Solutions ULC
Investigators
Principal Investigator: Katrina J Ruedy, MSPH Jaeb Center for Health Research
  More Information

Publications:
Responsible Party: T1D Exchange Clinic Network Coordinating Center
ClinicalTrials.gov Identifier: NCT01997411     History of Changes
Other Study ID Numbers: INGluc002
Study First Received: November 22, 2013
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by T1D Exchange Clinic Network Coordinating Center:
Diabetes Mellitus
Glucagon

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
Therapeutic Uses
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins

ClinicalTrials.gov processed this record on August 20, 2014