Investigation of the Impact of Different Application Volumes of Insulin Aspart in Subjects With Type 1 Diabetes

A Single-center, Randomized, Controlled, 2-period Cross-over, Open-labelled Trial to Evaluate the Impact of Different Application Volumes on Pharmacokinetic and Pharmacodynamic Properties of Insulin Aspart in Subjects With Type 1 Diabetes

Rationale: For the development of a closed loop system, faster insulin absorption after bolus administration could help to reduce the system's delay and thus increase patient safety. It has been shown that regular insulin absorption is faster when injecting insulin with a sprinkler needle (containing holes in the walls and being sealed at the tip). The current study will evaluate the impact of different application volumes on pharmacokinetic and pharmacodynamic properties of rapid acting insulin analogue (insulin aspart).

Objective: To compare the pharmacokinetic response (based on the time to maximum observed serum insulin concentration) and pharmacodynamic properties of rapid acting insulin aspart after subcutaneous injection of a defined dose (volume) at 1 versus 9 injection sites in patients with type 1 diabetes.

Study design: Monocentric, randomised, controlled, two-arm cross-over intervention study.

Population: Twelve type 1 diabetic subjects

Intervention: The investigational treatment is the subcutaneous administration of insulin aspart either as one bolus of 18 IU at one injection site or as 9 separately and simultaneously applied bolus of 2 IU each at 9 separate injection sites. Serum and plasma samples to assess pharmacodynamic and pharmacokinetic properties will be taken during an 8-hour clamp experiment. Patients will undergo both investigational treatments in a randomized order; between the two clamp visits there will be a wash-out period of 5-21 days.

Main study endpoint: Time to maximum observed serum insulin aspart concentration.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Insulin aspart; Drug: Insulin aspart

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent obtained after being advised of the nature of the study
• Male or female aged 18-60 years (both inclusive)
• Type 1 diabetes treated with multiple daily insulin injection or continuous subcutaneous insulin infusion for 12 months
• Fasting C-peptide < 0.3nmol/L
• Body mass index 20.0-28.0 kg/m² (both inclusive)
• HbA1c < 10%

Exclusion Criteria:

• Female of childbearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods
• Skin pathology or condition prohibiting needle insertion/insulin administration as judged by the investigator
• History of bleeding disorder
• Current participation in another clinical study
• Significant acute or chronic illness that might interfere with subject safety or integrity of results as judged by the investigator
• Smoker (defined as >5 cigarettes/d)
• Lipodystrophy
• Current treatment with systemic (oral or i.v.) corticosteroids, monoamine oxidase (MAO) inhibitors, non-selective beta-blockers, growth hormone, herbal products or non-routine vitamins. Furthermore, thyroid hormones are not allowed unless the use of these has been stable during the past 3 months.
• Significant history of alcoholism or drug abuse or a positive result in urine drug/alcohol screen.

Study Day Exclusion Criteria:

• Strenuous exercise within the last 24 hours prior to dosing.
• Non-fasting (i.e. consumption of food or beverages, other than water, later than 22:00 hours the evening before the visit) except if slight intake of rapidly absorbable carbohydrates has been necessary in order to prevent hypoglycaemia.
• Injection of long-acting insulin (e.g. insulin glargine or insulin detemir) later than 12:00 hours (noon), 2 days before the dosing visit.
• Injection of NPH insulin or other intermediate-acting insulin products later than 12:00 hours (noon) on the day before the dosing visit.
• Injection of any short acting insulin (aspart, lispro, glulisine) or more than 6 IU of human insulin between 22:00 hours and 03:00 hours the night before the dosing visit.
• Injection of any insulin later than 03:00 hours the night before the dosing visit.
• Infusion of any insulin later than 03:00 hours the night before the dosing visit for subjects using continuous subcutaneous insulin infusion (CSII).
• Positive result of alcohol breath test.
• Any medical condition that, in the opinion of the Investigator, could interfere with insulin pharmacokinetics and/or glucose metabolism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 bolus of insulin aspart 18 IU; Subcutaneous administration of insulin aspart as one bolus of 18 IU at one injection site.	Drug: Insulin aspart; Application of 18 IU insulin aspart as one bolus at one injection site; Drug: Insulin aspart; Application of 18 IU insulin aspart as 9 bolus of 2 IU each at nine injection sites
Experimental: 9 bolus of insulin aspart a 2 IU; Subcutaneous administration of insulin aspart as 9 separately and simultaneously applied bolus of 2 IU at 9 separate injection sites	Drug: Insulin aspart; Application of 18 IU insulin aspart as one bolus at one injection site; Drug: Insulin aspart; Application of 18 IU insulin aspart as 9 bolus of 2 IU each at nine injection sites

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tmax(ins), time to maximum observed serum insulin aspart concentration	8 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
t10%max(ins), time to reach 10% of maximum observed serum insulin aspart concentration	8 hours

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: European Commission

Publications and helpful links

Helpful Links

• Medical University of Graz

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: May 23, 2011
• First Submitted That Met QC Criteria: July 20, 2011
• First Posted (Estimate): July 21, 2011

Study Record Updates

• Last Update Posted (Estimate): April 20, 2012
• Last Update Submitted That Met QC Criteria: April 19, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Type 1 diabetes; Pharmacodynamics; Insulin aspart; Glucose clamp; Rapid Acting Insulin Analog
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: SPRINK-01