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

Hypoglycemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02081014
• Other study ID #: XSMP-201
• Secondary ID: 1R44DK096715-01A
• Status: Completed
• Phase: Phase 2
• First received: March 4, 2014
• Last updated: March 10, 2018
• Start date: March 2014
• Est. completion date: November 2014

Study information

• Verified date: March 2018
• Source: Xeris Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Drug:
• G-Pen Mini™ (glucagon injection)
stable, pre-mixed, liquid glucagon for subcutaneous injection

Locations

Country	Name	City	State
United States	Baylor College of Medicine, Children's Nutritional Research Center, Texas Children's Hospital	Houston	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Xeris Pharmaceuticals	Emissary International LLC, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serious Adverse Events	Number of serious adverse events (SAEs) per treatment	From first dose until follow-up call, up to 7 weeks per subject
Secondary	Glucagon Cmax (Fasting)	Pharmacokinetic parameter: Maximum concentration of glucagon	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection
Secondary	Glucagon Cmax (Post-insulin)	Pharmacokinetic parameter: Maximum concentration of glucagon	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
Secondary	Glucagon Area Under the Curve (AUC) (Fasting)	Pharmacokinetic parameter: Area under the glucagon concentration curve from 0 to 120 minutes	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
Secondary	Glucagon AUC (Post-insulin)	Pharmacokinetic parameter: Area under the glucagon concentration curve from 0 to 120 minutes	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
Secondary	Glucagon Tmax (Fasting)	Pharmacokinetic parameter: Time to reach maximum concentration of glucagon	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection
Secondary	Glucagon Tmax (Post-insulin)	Pharmacokinetic parameter: Time to reach maximum concentration of glucagon	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
Secondary	Glucose Cmax (Fasting)	Pharmacodynamic parameter: Maximum concentration of glucose	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection
Secondary	Glucose Cmax (Post-insulin)	Pharmacodynamic parameter: Maximum concentration of glucose	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
Secondary	Glucose AUC (Fasting)	Pharmacodynamic parameter: baseline adjusted area under the glucagon concentration curve from 0 to 120 minutes	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
Secondary	Glucose AUC (Post-insulin)	Pharmacodynamic parameter: baseline adjusted area under the glucose concentration curve from 0-120 minutes	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection
Secondary	Glucose Tmax (Fasting)	Pharmacodynamic parameter: Time to reach maximum concentration of glucose	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 180 minutes post-injection
Secondary	Glucose Tmax (Post-insulin)	Pharmacodynamic parameter: Time to reach maximum concentration of glucose	Approximately 15 and 0 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, and 120 minutes post-injection