Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia (AMG102)
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.
|Hypoglycemia||Drug: glucagon Drug: Low dose novel formulation Drug: high dose novel formulation Drug: Medium dose novel formulation||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: 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|
- 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.
- 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.
- 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
|Study Start Date:||March 2012|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Active Comparator: SC glucagon injection 1 mg
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
Hide 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
- HCG beta serum pregnancy test (female patients).
- 12-lead ECG
Please refer to this study by its ClinicalTrials.gov identifier: NCT01556594
|Montreal, Quebec, Canada, H3P 3P1|
|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|