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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AMG Medical Inc.
ClinicalTrials.gov Identifier:
NCT01556594
First received: March 15, 2012
Last updated: August 9, 2014
Last verified: August 2014

March 15, 2012
August 9, 2014
March 2012
July 2012   (final data collection date for primary outcome measure)
  • Percentage of Responders [ Time Frame: Within 30 minutes of treatment with test article ] [ Designated as safety issue: No ]
    A responder will be defined as a subject who achieved normal blood glucose ( ≥3.8 mmol/L) within 30 minutes after treatment.
  • Participants With at Least One Adverse Event [ Time Frame: Safety evaluations were recorded from dosing up until 3 hours after dosing with test medication ] [ Designated as safety issue: Yes ]
    Safety and tolerability will be evaluated through the assessment of adverse events, physical examination, laboratory tests, vital signs and ECG.
  • Percentage of responders [ Time Frame: 25 minutes ] [ Designated as safety issue: No ]
    A responder will be defined as a patient with a glucose increment of ≥1.5 mmol/L within 15 minutes (Tonset ≤15 min) and for at least 10 minutes following treatment (i.e. Toffset-Tonset ≥10 min).
  • Number of subjects with adverse events [ Time Frame: dosing to 6 hours post-dose ] [ Designated as safety issue: Yes ]
    Safety and tolerability will be evaluated through the assessment of adverse events, physical examination, nasal examination, bilateral anterior rhinoscopy, laboratory tests, vital signs, ECG and nasal scores.
Complete list of historical versions of study NCT01556594 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: No ]
mean plasma glucose level after treatment with test article
  • Area under the serum concentration versus time curve (AUC) of glucagon [ Time Frame: dose to 3 hours post-dose ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) parameters of glucagon will be derived using non-compartmental analysis (NCA) based on raw concentrations and baseline-adjusted concentrations
  • Peak serum concentration (Cmax)of glucagon [ Time Frame: dose to 3 hours post-dose ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) parameters of glucagon will be derived using non-compartmental analysis (NCA) based on raw concentrations and baseline-adjusted concentrations
  • Peak plasma concentration (Cmax) of glucose [ Time Frame: dose to 3 hours post-dose ] [ Designated as safety issue: No ]
    Pharmacodynamic (PD) parameters will be derived using NCA to assess the exposure to glucose and duration of exposure above, below and within the normal glucose range. The normal range for glucose will be considered to be 3.8 to 6.0 mmol/L. PD parameters of glucose will be calculated using raw concentrations and baseline-adjusted concentrations.
  • Area under the plasma concentration versus time curve (AUC) of glucose [ Time Frame: dose to 3 hours post-dose ] [ Designated as safety issue: No ]
    Pharmacodynamic (PD) parameters will be derived using NCA to assess the exposure to glucose and duration of exposure above, below and within the normal glucose range. The normal range for glucose will be considered to be 3.8 to 6.0 mmol/L. PD parameters of glucose will be calculated using raw concentrations and baseline-adjusted concentrations.
Not Provided
Not Provided
 
Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia
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

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.

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
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Hypoglycemia
  • Drug: glucagon
    glucagon solution for injection containing 1 mg of glucagon Single subcutaneous injection
    Other Names:
    • Glucagon
    • Glucagon for injection (rDNA origin)
  • Drug: Low dose novel formulation
    Low dose novel formulation
    Other Name: Low dose novel formulation
  • Drug: high dose novel formulation
    high dose novel formulation
    Other Name: high dose novel formulation
  • Drug: Medium dose novel formulation
    Medium dose novel formulation
    Other Name: Medium dose novel formulation
  • Active Comparator: SC glucagon injection 1 mg
    SC injection
    Intervention: Drug: glucagon
  • Experimental: Low dose novel formulation
    Low dose novel formulation
    Intervention: Drug: Low dose novel formulation
  • Experimental: High dose novel formulation
    High dose novel formulation
    Intervention: Drug: high dose novel formulation
  • Experimental: Medium dose novel formulation
    Medium dose novel formulation
    Intervention: Drug: Medium dose novel formulation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
July 2012
July 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01556594
AMG102
No
AMG Medical Inc.
AMG Medical Inc.
Not Provided
Principal Investigator: Eric Sicard, MD Algorithme Pharma Inc
AMG Medical Inc.
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP