Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia (AMG102)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01556594
Recruitment Status : Completed
First Posted : March 16, 2012
Results First Posted : August 13, 2014
Last Update Posted : May 25, 2016
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:

Hypoglycemia is common in people with type 1 diabetes. Mild and moderate hypoglycaemia is normally treated by consuming oral carbohydrates. During an episode of severe hypoglycaemia however, the person with diabetes is unable to consume carbohydrates and requires help from another person. The current standard treatment for severe hypoglycemia is intravenous glucose or an injection of glucagon, which causes an increase of blood glucose, which allows the person with diabetes to recover sufficiently to consume carbohydrate.

AMG Medical is investigating a novel formulation of glucagon which may be easier to administer than the currently available glucagon formulations.

In this study, patients with Type 1 diabetes will receive injected insulin to reduce their blood glucose, and will then receive one of three doses of the new glucagon formulation or a dose of glucagon for injection, and their blood glucose will be measured for 3 hours.

The study hypothesis is that the new glucagon formulation will be as effective as the current injected formulation at raising blood glucose levels within 15 minutes.

Condition or disease Intervention/treatment Phase
Hypoglycemia Drug: glucagon Drug: Low dose novel formulation Drug: high dose novel formulation Drug: Medium dose novel formulation Phase 2

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Detailed Description:

On each study day patients will be admitted to the clinical site at least 10 hours prior to glucagon administration.

Each patient will be weighed in a hospital gown in the evening prior to glucagon administration to adjust the insulin infusion rate individually.

Blood glucose values will be measured using a bedside rapid glucose analyzer. Blood glucose levels will be controlled overnight prior to dosing.

On the morning of dosing after a supervised overnight fast, hypoglycemia will be induced by IV insulin infusion prior to dosing. Glucose levels will be measured throughout the IV insulin infusion process and once a value of ≤3.6 mmol/L is observed, the insulin infusion will be stopped and within 5 minutes, subjects will be treated with one of the four treatments.

Serial blood sampling for PK (glucagon) and PD (glucose) assessments will be performed before and after glucagon administration.

In addition to the blood sampling schedule for glucose PD measurement, glucose levels will also be measured regularly throughout the procedure with a beside glucose analyzer for safety monitoring of patients. Minimally, measurements will be performed at each PK/PD blood draw.

For each study period administration sites will be closely evaluated for tolerability.

Before departure about 6 hours after glucagon administration, the glucose and insulin dosing and their stabilization will be evaluated by the physician to ensure the safety of the patient.

These procedures will be applied for each period of the study.

Drug Administration Procedure

In each study period, a single dose of glucagon will be administered in the morning after a 10-hour overnight fast and following insulin-induced hypoglycemia, using either the new glucagon formulation or glucagon for injection.

Treatments 1 and 2 and 3 - New formulation:

Treatment 4 - Subcutaneous administration:

The approved dose level of 1 mg of glucagon will be injected under the skin

A nurse will be at the clinical site overnight before glucagon administration to ensure safety of the patients. In addition, the physician in charge will remain at the clinical site from the start of the insulin infusion in the morning until at least the first 6 hours following each glucagon administration to ensure patients are re-stabilized in their regular insulin medication before departure. The physician in charge will also remain available at all times during the entire period of the study.

End of the study The following post-study tests will be performed after the collection of the last blood sample of the study.

  • Physical examination
  • Laboratory tests
  • Biochemistry
  • Hematology
  • Urinalysis
  • HCG beta serum pregnancy test (female patients).
  • 12-lead ECG

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study to Investigate the Safety and Efficacy of 2 Dose Levels of a Novel Glucagon Formulation Compared to Commercially Available Glucagon in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia
Study Start Date : March 2012
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia
Drug Information available for: Glucagon
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: SC glucagon injection 1 mg
SC injection
Drug: glucagon
glucagon solution for injection containing 1 mg of glucagon Single subcutaneous injection
Other Name: Glucagon for injection (rDNA origin)
Experimental: Low dose novel formulation
Low dose novel formulation
Drug: Low dose novel formulation
Low dose novel formulation
Experimental: High dose novel formulation
High dose novel formulation
Drug: high dose novel formulation
high dose novel formulation
Experimental: Medium dose novel formulation
Medium dose novel formulation
Drug: Medium dose novel formulation
Medium dose novel formulation

Primary Outcome Measures :
  1. Percentage of Responders [ Time Frame: Within 30 minutes of treatment with test article ]
    A responder will be defined as a subject who achieved normal blood glucose ( ≥3.8 mmol/L) within 30 minutes after treatment.

  2. Participants With at Least One Adverse Event [ Time Frame: Safety evaluations were recorded from dosing up until 3 hours after dosing with test medication ]
    Safety and tolerability will be evaluated through the assessment of adverse events, physical examination, laboratory tests, vital signs and ECG.

Secondary Outcome Measures :
  1. Mean Peak Plasma Concentration (Cmax) of Glucose [ Time Frame: Samples were obtained at 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2.0, 2.5 and 3.0 hours after glucagon administration ]
    mean plasma glucose level after treatment with test article

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • History of type 1 diabetes between 2 and 30 years
  • Receiving daily insulin injections or insulin pump therapy for at least 2 years
  • If patient is taking Lantus, Levemir or equivalent once-daily in the evening as basal insulin, must be willing to transition to once-daily in the morning at least 48 hours prior to 1st dosing, and to follow this dosing regimen for the entire duration of the study
  • Body mass index (BMI) greater than or equal to 20.00 and below or equal to 33.00 kg/m2
  • Female patients must not be pregnant, and must be using effective contraception.
  • Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day for at least 3 months before day 1 of this study. An ex smoker is defined as someone who completely stopped smoking for at least 6 months before day 1 of this study

Exclusion Criteria:

  • History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the previous 6 months before day 1 of this study
  • Score ≥4 on the Clarke Hypoglycemia Awareness survey at screening
  • Presence or history of pheochromocytoma (i.e. adrenal gland tumor)
  • Presence or history of significant upper respiratory or allergic (i.e., seasonal rhinitis) disease
  • Presence of clinically significant findings on nasal examination and bilateral anterior rhinoscopy
  • Known presence of hereditary problems of galactose and /or lactose intolerance
  • History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (like angioedema) to any drugs

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 identifier (NCT number): NCT01556594

Canada, Quebec
Algorithme Pharma
Montreal, Quebec, Canada, H3P 3P1
Sponsors and Collaborators
Eli Lilly and Company
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

Responsible Party: Eli Lilly and Company Identifier: NCT01556594     History of Changes
Other Study ID Numbers: 16416
I8R-MC-IGBA ( Other Identifier: Eli Lilly and Company )
AMG102 ( Other Identifier: Locemia Solutions ULC )
First Posted: March 16, 2012    Key Record Dates
Results First Posted: August 13, 2014
Last Update Posted: May 25, 2016
Last Verified: April 2016

Keywords provided by Eli Lilly and Company:
Diabetes mellitus

Additional relevant MeSH terms:
Glucose Metabolism Disorders
Metabolic Diseases
Glucagon-Like Peptide 1
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs