Safety and Efficacy of a Novel Glucagon Formulation in Type 1 Diabetic Patients Following Insulin-induced Hypoglycemia - Full Text View

Purpose

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	Intervention	Phase
Hypoglycemia	Drug: glucagon Drug: low dose experimental formulation Drug: high dose experimental formulation Drug: Medium dose experimental glucagon formulation	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study 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

Resource links provided by NLM:

MedlinePlus related topics: Blood Sugar Diabetes Diabetes Medicines Hypoglycemia

Drug Information available for: Glucagon

U.S. FDA Resources

Further study details as provided by AMG Medical Inc.:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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.

Estimated Enrollment:	18
Study Start Date:	March 2012
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 mg comparator glucagon injection subcutaneous glucagon injection containing 1 mg of glucagon	Drug: glucagon glucagon solution for injection containing 1 mg of glucagon Single subcutaneous injection
Experimental: low dose glucagon experimental formulation low dose of glucagon experimental formulation	Drug: low dose experimental formulation low dose AMG504-1 experimental formulation
Experimental: high dose experimental formulation High dose AMG504-1 experimental formulation	Drug: high dose experimental formulation high dose AMG504-1 experimental glucagon formulation
Experimental: Medium dose glucagon experimental formulaton medium dose AMG504-1 experimental formulation	Drug: Medium dose experimental glucagon formulation Medium dose AMG504-1 experimental formulation

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556594

Locations

Canada, Quebec
Algorithme Pharma	Recruiting
Montreal, Quebec, Canada, H3P 3P1
Contact: Marc Lefebvre, MD (450) 973-6077 ext 2224 mlefebvre@algopharm.com
Contact: Marianne Rufiange, PhD 450-973-3155 ext 2407 mrufiange@algopharm.com
Principal Investigator: Eric Sicard, MD

Sponsors and Collaborators

AMG Medical Inc.

Investigators

Principal Investigator:

Eric Sicard, MD

Algorithme Pharma Inc

More Information

No publications provided

Responsible Party:	AMG Medical Inc.
ClinicalTrials.gov Identifier:	NCT01556594 History of Changes
Other Study ID Numbers:	AMG102
Study First Received:	March 15, 2012
Last Updated:	May 14, 2012
Health Authority:	Canada: Health Canada United States: Food and Drug Administration

Keywords provided by AMG Medical Inc.:

Hypoglycemia
Diabetes mellitus

Additional relevant MeSH terms:

Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Glucagon
Glucagon-Like Peptide 1
Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Incretins

ClinicalTrials.gov processed this record on May 23, 2013

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