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Diabetes Mellitus, Type 1Phase 3NCT01994746

Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults

A Phase 3 study testing Nasal Glucagon and Intramuscular Glucagon in people with Diabetes Mellitus, Type 1, run by Eli Lilly and Company at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to assess the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of 3 milligrams (mg) glucagon (glucagon nasal powder) administered nasally compared with commercially available glucagon given by intramuscular injection. Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Nasal Glucagon and Intramuscular Glucagon
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
8 sitesUnited States
Study dates
Nov 2013to Jan 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • To be eligible, the following inclusion criteria must be met:
  • 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
  • At least 18.0 years of age and less than 65.0 years
  • Body mass index (BMI) greater than or equal to 20.0 and below or equal to 35.0 kilograms per meter squared (kg/m²)
  • Weighs at least 50 kg (110 pounds)
  • Females must meet one of the following criteria:
Show all 10Show fewer
  • Of childbearing potential but agree to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from the screening until study completion)
  • 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)
  • 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
  • Willingness to adhere to the study requirements

Who cannot join

  • An individual is not eligible if any of the following exclusion criteria are present:
  • Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are 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 interfere 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
Show all 11Show fewer
  • Use of daily systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs
  • History of epilepsy or seizure disorder
  • Regularly consumes 3 or more alcoholic beverages per day
  • Use of an Investigational Product in another clinical trial within the past 30 days
  • Donated 225 milliliters (mL) or more of blood in the previous 8 weeks before the first glucagon dosing

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Barbara Davis Center for Diabetes

    Aurora, Colorado, 80045

  • UPA Buffalo

    Buffalo, New York, 14222

  • University of Florida

    Gainesville, Florida, 32605

  • Riley Hospital for Children Indiana University Health

    Indianapolis, Indiana, 46202

  • University of Minnesota

    Minneapolis, Minnesota, 55454

  • Yale University

    New Haven, Connecticut, 06520

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Oregon Health and Science University

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: Efficacy and Safety of Nasal Glucagon for Treatment of Insulin Induced Hypoglycemia in Adults With Diabetes

The purpose of this study is to assess the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of 3 milligrams (mg) glucagon (glucagon nasal powder) administered nasally compared with commercially available glucagon given by intramuscular injection.

Read the detailed description

Each glucagon dosing visit was conducted after an overnight fast of at least 8 h with a starting plasma glucose >= 90 mg/dL. Hypoglycemia was induced by an intravenous (IV) infusion of regular insulin diluted in normal saline during the clinic visit. Five minutes after stopping the insulin infusion (once the plasma glucose was <60 mg/dL), participants were treated with either a 3 mg glucagon dose nasally or 1 mg of glucagon administered by intramuscular (IM) injection.

After a wash-out period of 7 days or more, participants returned to the clinic and the procedure repeated with each participant crossed over to the other treatment. As such, each participant underwent two episodes of insulin-induced hypoglycemia in random order and received glucagon nasal powder during one episode and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other episode.

Being tested
Nasal Glucagon, Intramuscular Glucagon
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nasal GlucagonDrug

    Also called AMG504-1, LY900018

  • Intramuscular GlucagonDrug

    Also called GlucaGen HypoKit

Study groups in NCT01994746
Study groupRoleWhat they receive
Nasal GlucagonExperimentalAt one visit, a glucagon dose of 3 mg was administered in a nostril with a prefilled delivery device that delivers a single dose upon activation.
Receives: Drug: Nasal Glucagon
Intramuscular GlucagonActive comparatorAt a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular [IM]).
Receives: Drug: Intramuscular Glucagon

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir

    Increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level defines treatment success. Due to the residual activity of circulating insulin, glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes following glucagon administration.

    Measured: Within 30 minutes after receiving glucagon at both dosing visits (glucose was measured at pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration)

Secondary outcomes (9)

  1. Nasal and Non-nasal Effects/Symptoms

    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. 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 subject and reporting the median/IQR across participants).

    Measured: Pre-dose; 15, 30, 60, and 90 post glucagon administration

  2. Recovery From Symptoms of Hypoglycemia

    Recovery from hypoglycemia symptoms were assessed using the Edinburgh Hypoglycemia Scale. The Edinburgh Hypoglycemia Symptom Scale measures the intensity of 15 commonly experienced hypoglycemic symptoms on a 7-point Likert scale (1 = not present, 7 = very intense). The higher the score, the more intense the hypoglycemia symptoms. The sum of each symptom score would yield a range of 15 to 105 (i.e., 15 x 7 =105). The total score was calculated as the sum of each symptom score minus 15, and summarized at each time point by treatment group.

    Measured: Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon

  3. Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir

    The mean time from glucagon administration to blood glucose >/=70 mg/dL or an increase ≥20 mg/dL in blood glucose from nadir.

    Measured: Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration

  4. Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon

    Measured: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

  5. Maximum Change From Baseline Concentration (Cmax) of Glucagon

    Measured: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

  6. Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon

    Measured: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

  7. Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes

    Measured: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

  8. Maximum Change From Baseline Concentration (Cmax) of Glucose

    Measured: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

  9. Time to Maximum Change From Baseline Concentration (Tmax) of Glucose

    Measured: Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Nov 2013 (estimated)
  2. Study startNov 2013
  3. Primary completionJan 2015
  4. Study completionJan 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01994746
Sponsor's protocol ID
16422
Other IDs
INGluc001, I8R-MC-IGBC, AMG106
Status last verified
Sep 2019
First submitted
20 Nov 2013
Last updated
23 Sep 2019
Data monitoring committee
No
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Publications

  • Rickels MR, Ruedy KJ, Foster NC, Piche CA, Dulude H, Sherr JL, Tamborlane WV, Bethin KE, DiMeglio LA, Wadwa RP, Ahmann AJ, Haller MJ, Nathan BM, Marcovina SM, Rampakakis E, Meng L, Beck RW; T1D Exchange Intranasal Glucagon Investigators. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care. 2016 Feb;39(2):264-70. doi: 10.2337/dc15-1498. Epub 2015 Dec 17.

    PubMed 26681725

  • Seaquist E, Gimenez M, Yan Y, Matsuhisa M, Kao CY, Wadwa RP, Nagai Y, Khunti K. Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials. J Endocr Soc. 2024 Feb 26;8(4):bvae034. doi: 10.1210/jendso/bvae034. eCollection 2024 Feb 19.

    PubMed 38444629

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nasal Glucagon and Intramuscular Glucagon in people with Diabetes Mellitus, Type 1, run by Eli Lilly and Company at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir (time frame: Within 30 minutes after receiving glucagon at both dosing visits (glucose was measured at pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01994746, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2019.

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