Effectiveness and Safety of Intranasal Glucagon for Treatment of Hypoglycemia in Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by T1D Exchange Clinic Network Coordinating Center
Sponsor:
Collaborator:
AMG Medical Inc.
Information provided by (Responsible Party):
T1D Exchange Clinic Network Coordinating Center
ClinicalTrials.gov Identifier:
NCT01994746
First received: November 20, 2013
Last updated: January 9, 2014
Last verified: January 2014
  Purpose

The primary objective of this study is to assess the effectiveness and safety of 3 mg glucagon (AMG504-1) administered as a puff into the nose compared with commercially-available glucagon given by injection.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Drug: Intranasal Glucagon
Drug: Glucagon
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: Efficacy and Safety of Intranasal Glucagon for Treatment of Insulin Induced Hypoglycemia in Adults With Diabetes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Increase in plasma glucose level to >=70mg/dL or an increase of >=20mg/dL [ Time Frame: within 30 minutes after receiving glucagon ] [ Designated as safety issue: Yes ]
    Increase in blood glucose to >=70 mg/dL or an increase of >=20 mg/dL within 30 minutes after receiving glucagon, without receiving additional actions to increase the blood glucose level such as oral or intravenous glucose or additional glucagon.


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.

  • Recovery from symptoms of hypoglycemia [ Time Frame: plasma glucose <75 mg/dl to 60 minutes following administration of glucagon ] [ Designated as safety issue: No ]
    Recovery from clinical symptoms of hypoglycemia if present as documented using the hypoglycemia symptoms questionnaire which is completed when the plasma glucose reaches <75 mg/dL and at 15, 30, 45 and 60 minutes following administration of glucagon.

  • Time from glucagon administration to return of plasma glucose to >/=70 mg/dL [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: No ]
  • Area under the curve from time zero to the last quantifiable concentration (AUC0-t) of glucagon [ Time Frame: 0 to 90 minutes following glucagon administration ] [ 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 ]
  • 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 ]
  • Maximum concentration (Cmax) of glucose [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: Yes ]
  • Time to maximum concentration (Tmax) of glucose [ Time Frame: 0 to 90 minutes following glucagon administration ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 82
Study Start Date: November 2013
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intranasal glucagon
A glucagon dose of 3 mg (equivalent to 30 mg of AMG 504-1 dry powder) 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
1 mg of commercially available recombinant human glucagon United States Pharmacopeia (USP) will be constituted in the provided prefilled disposable syringe containing 1 mL of diluting solution for injection into the deltoid muscle of the non-dominant arm.
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.

The procedure to evaluate the efficacy of AMG504-1 consists essentially of inducing hypoglycemia by an intravenous (IV) infusion of regular insulin diluted in normal saline. The insulin infusion will be used to decrease the glucose to a target <50 mg/dL. The insulin infusion will be stopped once the plasma glucose is <60 mg/dL. Five minutes after stopping the insulin infusion, participants will be treated with either a 3 mg glucagon dose intranasally or 1 mg of glucagon administered by intramuscular (IM) injection in the deltoid muscle of the non-dominant arm. During the 5-minute period after the insulin infusion has stopped, the glucose level is expected to continue to decrease an additional 15-20 mg/dL.

It is believed that a nadir of <50 mg/dL will be low enough to generate clinical symptoms in most participants yet high enough to avoid impairment of consciousness. 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 will return to the clinic and the procedure repeated with each participant crossed over to the other treatment. As such, each participant will undergo two episodes of insulin-induced hypoglycemia in random order and receive AMG504-1 during one episode and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other episode.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  1. 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.
  2. At least 18.0 years of age and less than 65.0 years.
  3. Body mass index (BMI) greater than or equal to 20.0 and below or equal to 35.0 kg/m2
  4. Weighs at least 50 kg (110 lbs)
  5. 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 is in a menopausal state (at least 1 year without menses).
  6. 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.
  7. Willingness to adhere to the protocol requirements

Exclusion Criteria:

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

  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. Regularly consumes 3 or more alcoholic beverages per day.
  9. Use of an Investigational Product in another clinical trial within the past 30 days
  10. Donated 225 mL or more of blood in the previous 8 weeks before the 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: NCT01994746

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 Not yet 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         
United States, Indiana
Riley Hospital for Children Indiana University Health Not yet 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
Joslin Diabetes Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Astrid Atakov Castillo    617-309-1997    astrid.atakov-castillo@joslin.harvard.edu   
Principal Investigator: Howard Wolpert, MD         
Sub-Investigator: Chuanyun Gao, MD         
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: John-Paul Lock, MD         
United States, Minnesota
University of Minnesota Not yet 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         
United States, New York
UPA Buffalo 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         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Jennifer Cox    503-494-9836    coje@ohsu.edu   
Contact: Bethany Wollam, CCRP    503-494-4392    wollamb@ohsu.edu   
Principal Investigator: Andrew Ahmann, MD         
Sub-Investigator: Bethany Klopfenstein, MD         
Sub-Investigator: Jessica Castle, MD         
Sub-Investigator: Farahnaz Joarder, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Patricia Bourne, RN, MSN, CDE    215-662-7616    patricia.bourne@uphs.upenn.edu   
Principal Investigator: Michael R Rickels, MD         
Sub-Investigator: Anastassia Amaro, MD         
Sponsors and Collaborators
T1D Exchange Clinic Network Coordinating Center
AMG Medical Inc.
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: NCT01994746     History of Changes
Other Study ID Numbers: INGluc001
Study First Received: November 20, 2013
Last Updated: January 9, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Glucagon
Glucagon-Like Peptide 1
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Incretins

ClinicalTrials.gov processed this record on July 26, 2014