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

This study has been completed.
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emissary International LLC
Information provided by (Responsible Party):
Xeris Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02081001
First received: March 4, 2014
Last updated: June 21, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Hypoglycemia
Drug: Novo Nordisk GlucaGen®
Drug: G-Pump™ (glucagon infusion)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Comparison of Pharmacokinetic and Pharmacodynamic Profiles of G-Pump™ (Glucagon Infusion) vs. GlucaGen® Delivered Subcutaneously to Subjects With Type 1 Diabetes (T1DM)

Resource links provided by NLM:


Further study details as provided by Xeris Pharmaceuticals:

Primary Outcome Measures:
  • Time to Reach 50% of Maximum Glucose Concentration (Glucose T50%-Early) [ Time Frame: 0 to 150 minutes post-dosing ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 to 150 minutes post-dosing ] [ Designated as safety issue: No ]
    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:
  • Glucagon Cmax [ Time Frame: From 0 to 150 minutes post-dosing ] [ Designated as safety issue: No ]
    Maximum plasma concentration of glucagon

  • Glucose Cmax [ Time Frame: From 0 to 150 minutes post-dosing ] [ Designated as safety issue: No ]
    Maximum plasma concentration of glucose

  • Glucagon Tmax [ Time Frame: From 0 to 150 minutes post-dosing ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration of glucagon

  • Glucose Tmax [ Time Frame: From 0 to 150 minutes post-dosing ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration of glucose

  • Glucagon AUC [ Time Frame: From 0 to 150 minutes post-dosing ] [ Designated as safety issue: No ]
    Area under the plasma concentration time curve for glucagon

  • Glucose AUC [ Time Frame: From 0 to 150 minutes post-dosing ] [ Designated as safety issue: No ]
    Area under the plasma concentration time curve for glucose

  • Infusion Site Discomfort Score at 10 Minutes [ Time Frame: At 10 minutes post-dosing ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At 30 minutes post-dosing ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 19
Study Start Date: March 2014
Study Completion Date: September 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Novo Nordisk GlucaGen®
single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg
Drug: G-Pump™ (glucagon infusion)
single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg
Active Comparator: Novo Nordisk GlucaGen®
Novo Nordisk GlucaGen®; single subcutaneous infusion doses 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg
Drug: Novo Nordisk GlucaGen®
single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg
Drug: G-Pump™ (glucagon infusion)
single subcutaneous infusion doses at 0.3 μg/kg, 1.2 μg/kg and 2.0 μg/kg

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02081001

Locations
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Xeris Pharmaceuticals
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emissary International LLC
Investigators
Principal Investigator: Jessica Castle, MD Oregon Health and Science University
  More Information

Responsible Party: Xeris Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02081001     History of Changes
Other Study ID Numbers: XSGO-201  4R44DK096706-02 
Study First Received: March 4, 2014
Results First Received: May 13, 2016
Last Updated: June 21, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Xeris Pharmaceuticals:
Hypoglycemia
Glucagon
Artificial Pancreas

Additional relevant MeSH terms:
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Glucagon
Glucagon-Like Peptide 1
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins

ClinicalTrials.gov processed this record on September 27, 2016