Metabolic Effect of Insulin Aspart and Human Insulin in Different Doses

Study Overview
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Brief Summary
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The metabolic effect of three different doses of insulin aspart and human insulin are investigated with the euglycaemic glucose clamp technique.

Detailed Description
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Double-blind, randomized, 6-period cross-over study in 16 healthy subjects. Each patient participates in 6 euglycemic glucose clamp experiments each. The time interval between the study days is 2 to 28 days. At the clamp visits, subjects are connected to a Biostator (MTB Medizintechnik, Ulm, Germany) and receive an intravenous human insulin infusion (rate of 0.15 mU/kg/min) over the duration of each experiment to prevent a rise in endogenous insulin secretion. After a baseline period of 2 h the trial drug (6, 12, or 24 U of either Insulin Aspart or regular human insulin in random order) are administered s.c. with a syringe into the abdominal wall. Glucose infusion rates (GIR) necessary to keep blood glucose concentrations close to the clamp level of 90 mg/dl (5 mmol/l) are administered and recorded by the Biostator every minute for a period of 12 h post-dosing. Blood samples are drawn at regular intervals for the analysis of C-peptide and (depending on the trial drug administered) serum insulin or serum Insulin Aspart concentrations (measured with specific ELISAs).

Official Title
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Pharmacodynamic and Pharmacokinetic Properties of Insulin Aspart: Dose - Ranging vs. Human Soluble Insulin

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: insulin aspart
* Drug: human regular insulin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed informed consent obtained before any trial-related activities Healthy subjects between 18 and 45 years inclusive Considered generally healthy upon completion of medical history and physical examination Body mass index (BMI) < 27 kg/m2 HbA1c < 6,1 % Non-smoker for at least three months Females of childbearing potential using acceptable methods of contraception, including tubal ligation, an intrauterine device (IUD), the oral contraceptive pill or barrier methods. Exclusion Criteria: Participation in any other clinical trial and receipt of any investigational drug within four weeks prior to this trial Previous participation in this trial Clinically significant abnormal haematology or biochemistry screening test Any disease requiring use of non topical prescription medicines Any serious systemic infectious disease that occurred in the four weeks prior to the first dose of test drug Any intercurrent illness that may affect blood glucose Current addiction to alcohol or substances of abuse as determined by the investigator Known or suspected allergy against insulin or any component of the composition of the trial drug Blood donation > 500 ml within the last nine weeks Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation If female, subject is pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>6 U insulin aspart | Drug: insulin aspart<br>* 6, 12, 24 U s.c.<br>* Other names: Novorapid;|
| Experimental: 2<br>12 U insulin aspart | Drug: insulin aspart<br>* 6, 12, 24 U s.c.<br>* Other names: Novorapid;|
| Experimental: 3<br>24 U insulin aspart | Drug: insulin aspart<br>* 6, 12, 24 U s.c.<br>* Other names: Novorapid;|
| Active Comparator: 4<br>6 IU human regular insulin | Drug: human regular insulin<br>* 6, 12 and 24 IU sc<br>* Other names: Actrapid;|
| Active Comparator: 5<br>12 IU human regular insulin | Drug: human regular insulin<br>* 6, 12 and 24 IU sc<br>* Other names: Actrapid;|
| Active Comparator: 6<br>24 IU human regular insulin | Drug: human regular insulin<br>* 6, 12 and 24 IU sc<br>* Other names: Actrapid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC GIR 360-720 min |  | at each dosing (6 times during the trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK endpoints such as C max/ins, t max/ins, AUC ins 0-120 min, AUC ins 360-720 min, AUC ins 0-720 min |  | at each dosing visit (6 times during the study) | 
| PD endpoints like GIR max, t max/GIR, AUC GIR 0-120 min, AUC GIR 0-720 min, t >2/GIR, early and late t 50%/GIR |  | at each dosing visit (6 times during the study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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euglycaemic glucose clamp, duration of action, late metabolic activity, hypoglycaemia