Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Steven J. Russell, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT02018627
First received: December 16, 2013
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

This study will test the hypothesis that micro-doses of Xerisol Glucagon (Xeris Pharmaceuticals) will be non-inferior by pharmacokinetic and pharmacodynamic criteria vs. micro-doses of Glucagon for Injection (Eli Lilly).


Condition Intervention Phase
Type 1 Diabetes
Drug: Xeris glucagon
Drug: Lilly glucagon
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • tmax [ Time Frame: 1 day visit ] [ Designated as safety issue: No ]
    tmax for Xeris vs. Lilly (non-inferiority)


Secondary Outcome Measures:
  • AOCGIR [ Time Frame: 1 day visit ] [ Designated as safety issue: No ]
    Area over the curve for glucose infusion rate in the hour following administration (AOCGIR) for Xeris vs. Lilly (non-inferiority)

  • GIRmax [ Time Frame: 1 day visit ] [ Designated as safety issue: No ]
    Maximal glucose infusion rate (GIRmax) for Xeris vs. Lilly (non-inferiority)

  • t½max [ Time Frame: 1 day visit ] [ Designated as safety issue: No ]
    Glucagon t½max for Xeris vs. Lilly (non-inferiority)

  • Injection pain [ Time Frame: immediately after injection ] [ Designated as safety issue: Yes ]

    Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly:

    -Injection pain on a 10 cm standard VAS: 0 = no pain, 10 = worst imaginable pain


  • Injection site erythema [ Time Frame: within 1 hour of injection ] [ Designated as safety issue: Yes ]

    Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly:

    -Injection site erythema or other local reaction, maximum diameter within 1 hour of injection


  • Maximal nausea [ Time Frame: within 1 hour of injection ] [ Designated as safety issue: Yes ]

    Quantitation of adverse events related to glucagon injection for Xeris vs. Lilly:

    -Maximal nausea within 1 hour of injection on a 10 cm VAS: no nausea = 0, vomiting = 10


  • Dermal response (Draize scale for erythema and eschar formation) [ Time Frame: within 1 hour of injection ] [ Designated as safety issue: Yes ]
    Grade on the erythema and eschar formation portion of the Draize scale for dermal response

  • Dermal response (Draize scale grade for edema formation) [ Time Frame: within 1 hour of injection ] [ Designated as safety issue: Yes ]
    Grade on the edema formation portion of the Draize scale for dermal response


Estimated Enrollment: 30
Study Start Date: April 2014
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Xeris glucagon
Xeris glucagon 50 micrograms, subcutaneous injection
Drug: Xeris glucagon
Active Comparator: Lilly glucagon
Lilly glucagon 30 micrograms, subcutaneous injection
Drug: Lilly glucagon

Detailed Description:

This study will test the hypothesis that micro-doses of a new formulation of stable glucagon, Xerisol Glucagon (Xeris Pharmaceuticals), will be non-inferior by pharmacokinetic and pharmacodynamic criteria vs. micro-doses of a freshly reconstituted formulation of glucagon that has poor stability in solution, Glucagon for Injection (Eli Lilly).

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 21 to 80 years old with type 1 diabetes for at least one year.
  • Diabetes managed using an insulin infusion pump using rapid-acting insulin such as insulin aspart (NovoLog), insulin lispro (Humalog), and insulin glulisine (Apidra) for at least one week prior to enrollment.

Exclusion Criteria:

  • Unable to provide informed consent.
  • Unable to comply with study procedures.
  • Current participation in another diabetes-related clinical trial that, in the judgment of the principle investigator, will compromise the results of the clamp study or the safety of the subject.
  • Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception.
  • End stage renal disease on dialysis (hemodialysis or peritoneal dialysis).
  • Hemoglobin < 11.5 gm/dl.
  • History of pheochromocytoma. Fractionated metanephrines will be tested in patients with history increasing the risk for a catecholamine secreting tumor (paroxysms of tachycardia, pallor, or headache; personal or family history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease; episodic or treatment of refractory hypertension, defined as requiring 4 or more medications to achieve normotension).
  • History of adverse reaction to glucagon (including allergy) besides nausea, vomiting, or headache.
  • Inadequate venous access as determined by study nurse or physician at time of screening.
  • Liver failure or cirrhosis.
  • Any other factors that, in the judgment of the principal investigator, would interfere with the safe completion of the study procedures.
  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: NCT02018627

Contacts
Contact: Courtney A Balliro, BS, RN 617-726-1242 cballiro@mgh.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Courtney A Balliro, BS, RN    617-726-1242    cballiro@mgh.harvard.edu   
Principal Investigator: Steven J Russell, MD PhD         
Sponsors and Collaborators
Steven J. Russell, MD, PhD
Investigators
Principal Investigator: Steven J Russell, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Steven J. Russell, MD, PhD, Assistant Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02018627     History of Changes
Other Study ID Numbers: 2013P002549
Study First Received: December 16, 2013
Last Updated: April 25, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
bionic pancreas
artificial pancreas
insulin
glucagon
clamp

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Glucagon
Glucagon-Like Peptide 1
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins

ClinicalTrials.gov processed this record on August 01, 2014