Clinical trial NCT02081014: Safety and Efficacy Study of Mini-Dose Glucagon (G-Pen Mini) in Patients With Type 1 Diabetes
Official title: A Randomized, Phase 2a, Blinded, 3-Way Crossover Dose-Ranging Study With G-Pen Mini™ (Glucagon Injection) to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Patients With Type 1 Diabetes Mellitus (T1DM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypoglycemia
Keywords: Hypoglycemia
Glucagon
Diabetes
Lead sponsor: Xeris Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Emissary International LLC
First posted: 2014-03-07
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Male and female subjects on insulin infusion pump therapy for treatment of type 1 diabetes
2. Between the ages of 18 and 50 years of age, inclusive, at Screening.
3. 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).
4. 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.
5. Hemoglobin A1c (HbA1c) \< 9.0 %.
6. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
7. Subjects must be willing and able to comply with scheduled visits, treatment, laboratory tests and study procedures.

Exclusion Criteria:

1. Clinical evidence of microvascular complication(s) other than mild microalbuminuria or history of mild non-proliferative retinopathy
2. Any chronic diseases or illness that interferes with glucose metabolism, except for T1DM, or medications other than hypothyroidism on appropriate thyroid hormone replacement.
3. Blood pressure (BP) readings at Screening where Systemic BP \<90 or \>140 mm Hg, and Diastolic BP \<50 or \>90 mm Hg.
4. 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.
5. Study participants who are pregnant at Screening.
6. Breast feeding must be discontinued if a subject wishes to participate in this study.
7. Positive test for hepatitis B, hepatitis C, or HIV found at Screening.
8. Positive urine drug test for illicit drugs at Screening.
9. History of allergies to glucagon, glucagon-like products or to any of the excipients in the investigational formulation.
10. Known presence of hereditary problems of glycogen storage disease, galactose and /or lactose intolerance
11. Administration of glucagon more than once within the three (3) months prior to Screening
12. 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
13. 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.
14. 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
15. 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.
16. 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.

Primary outcomes:
measure: Serious Adverse Events
timeFrame: From first dose until follow-up call, up to 7 weeks per subject
Secondary outcomes:
measure: Glucagon Cmax (Fasting)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection
measure: Glucagon Cmax (Post-insulin)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
measure: Glucagon Area Under the Curve (AUC) (Fasting)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
measure: Glucagon AUC (Post-insulin)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
measure: Glucagon Tmax (Fasting)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection
measure: Glucagon Tmax (Post-insulin)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
measure: Glucose Cmax (Fasting)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection
measure: Glucose Cmax (Post-insulin)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
measure: Glucose AUC (Fasting)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
measure: Glucose AUC (Post-insulin)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
measure: Glucose Tmax (Fasting)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection
measure: Glucose Tmax (Post-insulin)
timeFrame: Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine, Children's Nutritional Research Center, Texas Children's Hospital
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Morey W Haymond, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haymond MW, Redondo MJ, McKay S, Cummins MJ, Newswanger B, Kinzell J, Prestrelski S. Nonaqueous, Mini-Dose Glucagon for Treatment of Mild Hypoglycemia in Adults With Type 1 Diabetes: A Dose-Seeking Study. Diabetes Care. 2016 Mar;39(3):465-8. doi: 10.2337/dc15-2124. Epub 2016 Feb 9.