A Double-blinded, Randomised, Three-period Crossover Euglycaemic Clamp Trial Investigating the Pharmacokinetics, Glucodynamics and Safety of BioChaperone Human Insulin, Human Insulin (Huminsulin® Normal) and Insulin Lispro (Humalog®) in Subjects With Type 1 Diabetes

Study Overview
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Brief Summary
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The addition of BioChaperone to already marketed prandial human insulin preparations may accelerate the onset and shorten the duration of action due to facilitation of the insulin absorption after subcutaneous injection. The aim of the trial is to assess the efficacy and safety of BioChaperone human insulin in subjects with type 1 diabetes under a dose of 0.2 U/kg. This trial is a single center, randomised, double-blinded, three treatment, three-period cross-over, 10-hour euglycaemic clamp trial in subject with type 1 diabetes mellitus. Each subject will be randomly allocated to a single dose of BioChaperone human insulin 0.2 U/kg, a single dose of Huminsulin® Normal 0.2 U/kg and a single dose of Humalog® 0.2 U/kg on 3 separate dosing visits.

Official Title
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A Double-blinded, Randomised, Three-period Crossover Euglycaemic Clamp Trial Investigating the Pharmacokinetics, Glucodynamics and Safety of BioChaperone Human Insulin, Human Insulin (Huminsulin® Normal) and Insulin Lispro (Humalog®) in Subjects With Type 1 Diabetes

Conditions
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Diabetes Mellitus Type 1

Intervention / Treatment
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* Drug: BioChaperone human insulin
* Drug: Huminsulin® Normal
* Drug: Humalog®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subject with type 1 diabetes for at least 12 months Treated with multiple daily insulin injections or insulin pump (CSII) for at least 12 months Body mass index: 18.5-28.0 kg BW·m-2 HbA1c: ≤ 9.0% Exclusion Criteria: Diabetes mellitus type 2 Receipt of any investigational product within 3 months prior to first dosing of investigational product in this trial Clinically significant abnormalities as judged by the Investigator Any systemic treatment with drugs known to interfere with glucose metabolism History of alcoholism or drug/chemical abuse as per Investigator's judgement Use of any tobacco or nicotine-contained product within one year prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BioChaperone human insulin<br>BioChaperone Human Insulin | Drug: BioChaperone human insulin<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>Drug: Huminsulin® Normal<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>Drug: Humalog®<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>|
| Active Comparator: Human insulin<br>Huminsulin® Normal | Drug: BioChaperone human insulin<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>Drug: Huminsulin® Normal<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>Drug: Humalog®<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>|
| Active Comparator: Insulin lispro<br>Humalog® | Drug: BioChaperone human insulin<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>Drug: Huminsulin® Normal<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>Drug: Humalog®<br>* Single dose of 0.2 U/kg body weight injected subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUCins(0-1h)) | Area under the human insulin serum concentration - time curve from t=0 to 1 hour | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Early t0.5max ins/lisp | Time to first observed half maximum serum human insulin / insulin lispro concentration | up to 10 hours post administration | 
| Glucodynamics: Area under the glucose infusion rate - time curve from t=0 to 10 hours | Area under the glucose infusion rate - time curve from t=0 to 10 hours | 10 hours | 
| Glucodynamics: Early t0.5 Glucose Infusion Rate max (GIRmax) | Time to first observed half maximum glucose infusion rate | 10 hours | 
| Glucodynamics: GIRmax - Maximum glucose infusion rate | Maximum glucose infusion rate | 10 hours | 
| Pharmacokinetics: AUCins/lisp(0-10h): Area under the human insulin / insulin lispro serum concentration | Area under the human insulin / insulin lispro serum concentration - Time curve from t=0 to 10 hours | 10 hours | 
| Pharmacokinetics: Tmax(ins/lisp) - Time to maximum observed serum human insulin concentration and insulin lispro concentration | Time to maximum observed serum human insulin concentration and insulin lispro concentration | 10 hours | 
| Safety and tolerability: adverse events, local tolerability, vital signs variation, ECG, laboratory safety parameters | Adverse events, local tolerability, vital signs variation, ECG, laboratory safety parameters | up to 7 weeks | 
| Pharmacokinetics: Cmax(ins/lisp) | Maximum observed human insulin / insulin lispro serum concentration | up to 10 hours | 
| Glucodynamics: Area under the glucose infusion rate - time curve from t=0 to 2 hours | Area under the glucose infusion rate - time curve from t=0 to 2 hours | 2 hours post administration |