Clinical Trial: Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary:

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.

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.

Original Primary Outcome:

• Percentage of Responders [ Time Frame: 25 minutes ]
  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 ]
  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.

Current Secondary Outcome: 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 ]

Original Secondary Outcome:

• Area under the serum concentration versus time curve (AUC) of glucagon [ Time Frame: dose to 3 hours post-dose ]
  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 ]
  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 ]
  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 ]
  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.

Information By: Eli Lilly and Company

Dates:
Date Received: March 15, 2012
Date Started: March 2012
Date Completion:
Last Updated: April 26, 2016
Last Verified: April 2016