A Comparison of Pharmacodynamics and Pharmacokinetics of Insulin Aspart, Biphasic Insulin Aspart 30, 50 and 70.

Study Overview
=================
Brief Summary
-----------------
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. OBJECTIVE: The objective is to describe pharmacodynamic (PD) and pharmacokinetic (PK) profiles of Insulin Aspart (IAsp), Biphasic Insulin Aspart (BIAsp) 30, 50 and 70 for a period of 12 hours following a standard test meal on four days respectively in subjects with type 1 diabetes.

Detailed Description
-----------------
This trial is a single centre, open-label, randomised 4 period cross-over trial, comparing the pk and pd profiles of IAsp, BIAsp 30, BIAsp 50 and BIAsp 70 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 30, BIAsp 50 or BIAsp 70 at a test meal. The trial consists of a screening period of 4-21 days and 4 treatment visits

Official Title
-----------------
A Comparison of Pharmacodynamics and Pharmacokinetics of Insulin Aspart, Biphasic Insulin Aspart 30, 50 and 70. - A Randomised, Quadruple Cross-Over Trial

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Drug: NovoRapid, NovoMix 30, Bifasisk Insulin Aspart 50, BIAsp70


Participation Criteria
=================
Eligibility Criteria
-----------------
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 ≥ 0,5 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 > 2x 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. The receipt of any investigational drug within a three month period prior to this trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: NovoRapid, NovoMix 30, Bifasisk Insulin Aspart 50, BIAsp70|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint: |  |  | 
| • Cmaxglu: Peak plasma glucose following test meal (breakfast). A comparison will be made between BIAsp 50 vs BIAsp 70, BIAsp 30 vs BIAsp 70, BIAsp 30 vs BIAsp 50 and IAsp vs BIAsp 30, 50 and 70. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoints: |  |  | 
| 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 insulin aspart preparation: IAsp (NovoRapid®), Biphasic insulin aspart 30, 50 and 70. |  |  | 
| AUCins: The area under insulin aspart 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 insulin aspart preparation: IAsp (NovoRapid®), Biphasic insulin aspart 30, 50 and 70. |  |  |