Safety and Efficacy Study of Mini-Dose Glucagon (G-Pen Mini) in Patients With Type 1 Diabetes

Phase 2

Completed

Conditions: Hypoglycemia

Interventions: Drug: G-Pen Mini™ (glucagon injection)

Registration Number: NCT02081014

Lead Sponsor: Xeris Pharmaceuticals

Brief Summary: The purpose of the study is to demonstrate that mini-doses of stable liquid glucagon (G-Pen Mini) produced by Xeris Pharmaceuticals are safe and effective as a treatment for mild to moderate hypoglycemia, a complication of diabetes.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Male and female subjects on insulin infusion pump therapy for treatment of type 1 diabetes
Between the ages of 18 and 50 years of age, inclusive, at Screening.
Females of childbearing potential with a negative serum pregnancy test prior at screening and negative urine pregnancy tests prior to the Treatment visits, using an approved forms of contraception for the duration of participation in the study (i.e. until after last dose).
Male subjects are required to use a condom and another of the methods of contraception in #3 above starting at Randomization and for the duration of the study.
Hemoglobin A1c (HbA1c) < 9.0 %.
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
Subjects must be willing and able to comply with scheduled visits, treatment, laboratory tests and study procedures.

Exclusion Criteria

Clinical evidence of microvascular complication(s) other than mild microalbuminuria or history of mild non-proliferative retinopathy
Any chronic diseases or illness that interferes with glucose metabolism, except for T1DM, or medications other than hypothyroidism on appropriate thyroid hormone replacement.
Blood pressure (BP) readings at Screening where Systemic BP <90 or >140 mm Hg, and Diastolic BP <50 or >90 mm Hg.
Cardiovascular event within 6 months prior to screening such as unstable angina, acute coronary syndrome, myocardial infarction, therapeutic coronary procedure (e.g., stent placement, Percutaneous Transluminal Coronary Angioplasty (PTCA), Coronary Artery By-pass Grafting (CABG)), stroke or transient ischemic attack.
Study participants who are pregnant at Screening.
Breast feeding must be discontinued if a subject wishes to participate in this study.
Positive test for hepatitis B, hepatitis C, or HIV found at Screening.
Positive urine drug test for illicit drugs at Screening.
History of allergies to glucagon, glucagon-like products or to any of the excipients in the investigational formulation.
Known presence of hereditary problems of glycogen storage disease, galactose and /or lactose intolerance
Administration of glucagon more than once within the three (3) months prior to Screening
Subjects with any of the following abnormalities in clinical laboratory tests at Screening, confirmed by a single repeat, if necessary:
- Hemoglobin (Hb) below the lower limits of normal for the laboratory
- Total bilirubin above the upper limits of normal for the laboratory
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above the upper limits of normal for the laboratory
- Creatinine above the upper limits of normal for the laboratory
History of regular alcohol consumption as defined by alcohol intake in a quantity exceeding 7 drinks per week for females or 14 drinks per week for males, where 1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor.
Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before screening for the current study and during participation in the current study
Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed red blood cells, platelets or quantities less than 500 mL are allowed at investigator discretion.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
G-Pen Mini™ (glucagon injection) 75 ug	G-Pen Mini™ (glucagon injection)	G-Pen Mini™ (glucagon injection), two 75 microgram subcutaneous injections given approximately 4-5 hours apart
G-Pen Mini™ (glucagon injection) 150 ug	G-Pen Mini™ (glucagon injection)	G-Pen Mini™ (glucagon injection), two 150 microgram subcutaneous injections given approximately 4-5 hours apart
G-Pen Mini™ (glucagon injection) 300 ug	G-Pen Mini™ (glucagon injection)	G-Pen Mini™ (glucagon injection), two 300 microgram subcutaneous injections given approximately 4-5 hours apart

Primary Outcome Measures

Name	Time	Method
Serious Adverse Events	From first dose until follow-up call, up to 7 weeks per subject	Number of serious adverse events (SAEs) per treatment

Secondary Outcome Measures

Name	Time	Method
Glucagon Cmax (Fasting)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection	Pharmacokinetic parameter: Maximum concentration of glucagon
Glucagon Cmax (Post-insulin)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection	Pharmacokinetic parameter: Maximum concentration of glucagon
Glucagon Area Under the Curve (AUC) (Fasting)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection	Pharmacokinetic parameter: Area under the glucagon concentration curve from 0 to 120 minutes
Glucagon AUC (Post-insulin)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection	Pharmacokinetic parameter: Area under the glucagon concentration curve from 0 to 120 minutes
Glucagon Tmax (Fasting)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection	Pharmacokinetic parameter: Time to reach maximum concentration of glucagon
Glucagon Tmax (Post-insulin)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection	Pharmacokinetic parameter: Time to reach maximum concentration of glucagon
Glucose Cmax (Fasting)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection	Pharmacodynamic parameter: Maximum concentration of glucose
Glucose Cmax (Post-insulin)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection	Pharmacodynamic parameter: Maximum concentration of glucose
Glucose AUC (Fasting)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection	Pharmacodynamic parameter: baseline adjusted area under the glucagon concentration curve from 0 to 120 minutes
Glucose AUC (Post-insulin)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection	Pharmacodynamic parameter: baseline adjusted area under the glucose concentration curve from 0-120 minutes
Glucose Tmax (Fasting)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection	Pharmacodynamic parameter: Time to reach maximum concentration of glucose
Glucose Tmax (Post-insulin)	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection	Pharmacodynamic parameter: Time to reach maximum concentration of glucose