A Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of Very Low Dose-Glucagon in Subjects With Type 1 Diabetes Mellitus

Type 1 Diabetes Clinical Trial

Official title:

A Phase 1b, Single-Blind Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of Three Separate Dose Levels of Very Low Dose-Glucagon Administered Subcutaneously Overnight for 6, 9 or 12 Hours in Subjects With Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00304538
• Other study ID #: DIO-103
• Status: Completed
• Phase: Phase 1
• First received: March 16, 2006
• Last updated: August 21, 2006
• Start date: March 2006
• Est. completion date: July 2006

Study information

• Verified date: August 2006
• Source: DiObex
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to identify the safest dose of very low dose glucagon to prevent hypoglycemia in patients with Type I diabetes who use insulin pumps and to measure the the amount of glucagon in the blood and see how the body responds to the glucagon.

Description:

Glucagon is currently used to treat severe hypoglycemia. DiObex believes that glucagon replacement therapy with very low doses of glucagon may prevent hypoglycemia without compromising effective glycemic control by insulin. In this study very low doses of glucagon will administered to Type I diabetics who use insulin pumps. The glucagon will be administered subcutaneously overnight for 6, 9 or 12 hours to see if the number of mild or impending hypoglycemia events can be safely decreased. Three different doses of glucagon will be compared to a control infusion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Males or females, 18 to 55 years of age, requiring daily insulin for the management of type 1 diabetes mellitus for >10 years

2. On a stable basal insulin regimen using CSII therapy (“stable” defined as total daily dose of insulin not changed by more than ± 20% for 2 months prior to screening)

3. Glycosylated hemoglobin (HbA1c) =8.0%

4. Total daily insulin requirement of =1 unit/kg of body weight

5. Fasting C-peptide level of <1.0 ng/mL (<330 pmol/L) (may be done at screening or may be taken from subject’s medical record if performed within the past 12 months)

6. Body mass index (BMI) =25.5 kg/m2 and body weight over past 6 months within ± 5%

7. Hemoglobin, hematocrit, and platelets within normal limits; no clinically significant abnormality of white blood cells (WBC) or differential

8. Serum chemistry results within normal limits except for liver enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] which must be within 2.5 times upper limit of normal (ULN) and creatinine which must be <1.6 mg/dL

9. Normal thyroid stimulating hormone

10. No history of HIV infection and negative results for hepatitis B and C

11. Negative serum pregnancy test, non-lactating, and using adequate contraception, if female and of child bearing potential (intact uterus and pre-menopausal)

12. Medications for the treatment of high blood pressure and/or dyslipidemia are allowed if regimen stable for 2 months prior to screening

13. Medically stable as determined by history and physical examination, including vital signs

14. Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality

15. Willing and able to give written informed consent

Exclusion Criteria:

1. Participation in a clinical trial with or use of an investigational agent within 30 days of Study Visit 1.

2. History of atherosclerosis including coronary artery disease, angina pectoris, myocardial infarction, cerebrovascular accident, or transient ischemic attacks

3. History or symptoms of pheochromocytoma

4. History of any malignancy within 3 years except for basal cell skin cancer

5. Active infection, drug or alcohol abuse, eating disorder, or psychiatric disorder

6. Concomitant medications: systemic or potent topical steroids or medications that may affect blood glucose, e.g., sulfonylureas, alpha-glucosidase inhibitors, biguanides, meglitinides, thiazolidinediones

7. Any condition which increases the risk of participation in the trial in the opinion of the investigator -

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• very low dose (VLD) glucagon

Locations

Country	Name	City	State
United States	University Of California, San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
DiObex

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1) Evaluate the safety and tolerability of VLD-glucagon in doses of 2, 4 and 8 ng/kg/minute when infused overnight 2) Evaluate the PK profile in plasma of VLD-glucagon 3) Evaluate the pharmacodynamic activity of these doses by measuring glucose levels
Secondary	Compare the number of times and amount of time subjects have glucose levels < 70 mg/dL when treated with VLD-glucagon vs. the control infusion