Clinical trial NCT02018627: Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon
Official title: Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type 1 Diabetes
Keywords: bionic pancreas
artificial pancreas
insulin
glucagon
clamp
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2013-12-23
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).

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 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.

Primary outcomes:
measure: Tmax
timeFrame: every 2 minutes for 1 hour post-dose of each glucagon
Secondary outcomes:
measure: AOCGIR
timeFrame: every 2 minutes for 1 hour post-dose of each glucagon
measure: GIRmin
timeFrame: every 2 minutes for 1 hour post-dose of each glucagon
measure: t½Max
timeFrame: every 2 minutes for 1 hour post-dose of each glucagon
measure: Injection Pain
timeFrame: immediately after injection
measure: Injection Site Erythema
timeFrame: within 1 hour of injection
measure: Maximal Nausea
timeFrame: within 1 hour of injection
measure: Dermal Response (Draize Scale for Erythema and Eschar Formation)
timeFrame: within 1 hour of injection
measure: Dermal Response (Draize Scale Grade for Edema Formation)
timeFrame: within 1 hour of injection
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven J Russell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: