A Comparison of Pharmacodynamics and Pharmacokinetics of Insulin Aspart, BIAsp70, BIAsp50 and Fast-acting Human Insulin

Study Overview
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Brief Summary
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The hypothesis is that an optimal formulation of fast acting and intermediary acting insulin analogues will improve post prandial glycaemic control in patients with type 1 diabetes

Detailed Description
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This trial is a single centre, open-label, randomised 4 period cross-over trial, comparing the pk and pd profiles of IAsp, BIAsp 50, BIAsp 70 and Fast-acting Human Insulin after a standard test meal in subjects with type 1 diabetes. The profiles will be derived over a 12-hour period after subcutaneous injection in the abdominal region with a single dose of IAsp, BIAsp 50, BIAsp 70 or Fast-acting Human Insulin at a test meal. The trial consists of a screening period of 4-21 days and 4 treatment visits.

Official Title
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A Comparison of Pharmacodynamics and Pharmacokinetics of Insulin Aspart, Biphasic Insulin Aspart 70 and 50 & Fast-acting Human Insulin in Patients With Type 1 Diabetes, A Randomised, Quadruple Crossover Trial

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Insulin Aspart, BIAsp 70, BIAsp50, Human Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities. Diagnosed type 1 diabetes before the age of 40 and on insulin treatment within one year of diagnosis. Insulin treatment of any regime for more than one year at time of inclusion. Total insulin demand ≥ 0,4 U/IU/kg/24 hrs HbA1c between 7% and 12% (both values included). Age ≥ 18 years. BMI between 18 and 35 kg /m2 (including both values). Exclusion Criteria: Known or suspected allergy to trial product(s) or related products. Recurrent major hypoglycaemic episodes. Heart: Unstable Angina Pectoris, AMI < 12 months or heart insufficiency classified according to NYHA III-IV Blood Pressure: Severe uncontrolled hypertension with BP > 180/110 mmHg, sitting Liver: Impaired hepatic function corresponding to serum-ALAT or basic phosphatase > 2 x upper reference limit of the local laboratory. Kidneys: Impaired renal function corresponding to serum-creatinin > 150 μmol/l according to the local laboratory. Any disease judged by the investigator to affect the trial. Pregnancy, breast-feeding or the intention of becoming pregnant or fertile women not using adequate contraceptive measures - adequate contraceptive method is sterilisation, hysterectomy or current use of contraceptive pills or intra uterine device.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin therapy<br>Insulin Aspart, Biphasic Insulin Aspart 70 and 50 & Fast-acting Human Insulin | Drug: Insulin Aspart, BIAsp 70, BIAsp50, Human Insulin<br>* 0.2 U/IU/kg subcutaneous injection, single dose<br>* Other names: - Human Insulin: Actrapid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmaxglu: Peak plasma glucose following test meal (breakfast). A comparison will be made between fast-acting human insulin vs. IAsp, BIAsp 50 and BIAsp 70, IAsp vs BIAsp 50 and BIAsp 70, BIAsp 50 vs. BIAsp 70. |  | 12 hours following a standard test meal (breakfast) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCglu: The area under the plasma glucose concentration (0-12, 0-6, 6-12, 0-4, 4-8, 8-12 hours after test meal) after a single injection of one of the four insulins: IAsp, Biphasic insulin aspart 50 and 70 & fast-acting human insulin |  | 12 hours following a standard test meal (breakfast) | 
| AUCins: The area under insulin aspart/human insulin concentration (0-12, 0-6, 6-12, 0-4, 4-8, 8-12 hours after test meal) after a single injection of one of the four insulins: IAsp, Biphasic insulin aspart 50 and 70 & fast-acting human insulin |  | 12 hours following a standard test meal (breakfast) | 
| tmaxins: Time to maximum serum insulin aspart/human insulin concentration |  | 12 hours following a standard test meal (breakfast) | 
| Serum GH, total IGF-I, IGF-I bioactivity, IGFBP-1, IGFBP-2, binary complex of IGF-I, IGFBP-3 and the acid-labile subunit (ALS) |  | 12 hours following a standard test meal (breakfast) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes