PK/PD Study With G-Pump (Glucagon Infusion) in T1DM Patients

Phase 2

Completed

Conditions: Hypoglycemia

Interventions: Drug: Novo Nordisk GlucaGen®
Drug: G-Pump™ (glucagon infusion)

Registration Number: NCT02081001

Lead Sponsor: Xeris Pharmaceuticals

Brief Summary: The purpose of the study is to assess the safety, speed of absorption, and onset of action of G-Pump™ (glucagon infusion) at three subcutaneous doses as compared to Novo GlucaGen®, all delivered via an OmniPod® infusion pump to patients with type 1 diabetes.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Males or females diagnosed with type 1 diabetes mellitus for at least 24 months
Current usage of subcutaneous insulin pump treatment
Age 18-65 years
C-peptide level < 0.5 ng/ml
Willingness to follow all study procedures, including attending all clinic visits
Subject has provided informed consent and has signed and dated an informed consent form before any trial-related activities

Exclusion Criteria

Pregnant and/ or Lactating: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study.
HbA1c >10.0%
Renal insufficiency (serum creatinine of 1.2 mg/dL or greater)
Serum ALT or AST equal to or greater than 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as a serum albumin of less than 3.0 g/dL; or serum bilirubin of over 2.0.
Hematocrit of less than or equal to 34%
Congestive heart failure, NYHA class II, III or IV
History of coronary artery disease
Active foot ulceration
History of a cerebrovascular accident
Active alcohol abuse or substance abuse
Active malignancy, except basal cell or squamous cell skin cancers
Major surgical operation within 30 days prior to screening
Seizure disorder
Current administration of oral or parenteral corticosteroids
Use of an investigational drug within 30 days prior to screening
Bleeding disorder, treatment with warfarin, or platelet count below 50,000
Proliferative or severe non-proliferative retinopathy
Gastroparesis
Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease)
Insulinoma
Allergies to glucagon or glucagon-like products, or any history of significant hypersensitivity to glucagon or any related products.
Glycogen storage disease
Any concurrent illness, other than diabetes, that is not controlled by a stable therapeutic regimen
Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening.
Any reason the principal investigator deems exclusionary

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Novo Nordisk GlucaGen®	Novo Nordisk GlucaGen®	Novo Nordisk GlucaGen®; single subcutaneous infusion doses 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg
Novo Nordisk GlucaGen®	G-Pump™ (glucagon infusion)	Novo Nordisk GlucaGen®; single subcutaneous infusion doses 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg
G-Pump™ (glucagon infusion)	G-Pump™ (glucagon infusion)	G-Pump™ (glucagon infusion); single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg
G-Pump™ (glucagon infusion)	Novo Nordisk GlucaGen®	G-Pump™ (glucagon infusion); single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg

Primary Outcome Measures

Name	Time	Method
Time to Reach 50% of Maximum Glucose Concentration (Glucose T50%-Early)	0 to 150 minutes post-dosing	The onset of action was assessed by determining the time in minutes required to achieve 50% of the maximum plasma concentration of glucose following each dose of glucagon.
Time to Reach 50% of Maximum Glucagon Concentration (Glucagon T50%-Early)	0 to 150 minutes post-dosing	The speed of absorption was assessed by determining the time in minutes required to achieve 50% of the maximum plasma concentration of glucagon following each dose of glucagon.

Secondary Outcome Measures

Name	Time	Method
Glucagon Cmax	From 0 to 150 minutes post-dosing	Maximum plasma concentration of glucagon
Glucose Cmax	From 0 to 150 minutes post-dosing	Maximum plasma concentration of glucose
Glucagon Tmax	From 0 to 150 minutes post-dosing	Time to maximum plasma concentration of glucagon
Glucose Tmax	From 0 to 150 minutes post-dosing	Time to maximum plasma concentration of glucose
Glucagon AUC	From 0 to 150 minutes post-dosing	Area under the plasma concentration time curve for glucagon
Glucose AUC	From 0 to 150 minutes post-dosing	Area under the plasma concentration time curve for glucose
Infusion Site Discomfort Score at 10 Minutes	At 10 minutes post-dosing	Infusion site discomfort was assessed by the subjects using a 100 mm Visual Analog Scale (VAS) questionnaire at 10 minutes following the initiation of dosing. Subjects were asked to draw a vertical line across the horizontal scale to indicate their current level of discomfort from 0 = no discomfort to 100 = worst possible discomfort. The distance in mm from the left hand anchor to the the first point where the subject's mark crossed the horizontal scale was measured and reported as the infusion site discomfort score.
Infusion Site Discomfort Score at 30 Minutes	At 30 minutes post-dosing	Infusion site discomfort was assessed by the subject using a 100 mm Visual Analog Scale (VAS) questionnaire at 30 minutes following the initiation of dosing. Subjects were asked to draw a vertical line across the horizontal scale to indicate their current level of discomfort from 0 = no discomfort to 100 = worst possible discomfort. The distance in mm from the left hand anchor to the the first point where the subject's mark crossed the horizontal scale was measured and reported as the infusion site discomfort score.